Pancreatic cancer medical therapy: Difference between revisions

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__NOTOC__
__NOTOC__
{{Pancreatic cancer}}
{{Pancreatic cancer}}
{{CMG}}; '''Associate Editor-In-Chief:''' {{Cherry}}
{{CMG}}; {{AE}} {{Cherry}}
==Overview==
==Overview==
The therapy for pancreatic cancer depends largely on the disease progression and the stage of cancer. There are five different types of treatment for patients with pancreatic cancer: surgery, radiation therapy, chemotherapy, chemoradiation therapy and targeted therapy. In patients with pancreatic cancer, surgery is the primary modality of treatment. Extrapancreatic disease, in contrast, requires palliative therapy and curative resection is not performed in such patients. Curative resection is not contraindicated in all patients with vascular invasion. Involvement of the portal or superior mesenteric vein can be resected and reconstructed with the help of splenic, saphenous or internal jugular veins. Various methods of surgical resection may be employed and each of these has its own sets of risks and perioperative complications. The facts are discussed by the patient and surgical team before arriving at a well-informed decision. The method of surgical resection depends on the locally invasive characteristics of the neoplasm and size of the tumor. Patients with unresectable disease may be treated with chemotherapy and/or radiation therapy as a part of adjuvant or neoadjuvant therapy. Chemotherapy may be administered when surgical intervention is not deemed appropriate. The National Comprehensive Cancer Network (NCCN) has recommended guidelines for treatment in patients based on their performance status, which is a major prognostic factor. Performance status assesses extent of metastatic disease, size of the tumor and degree of weight loss. In patients with locally advanced unresectable or metastatic disease with good performance status,  a combination of Leucovorin,5-fuorouracil, Oxaliplatin and Irinotecan (FOLFIRINOX) is preferred.
In patients with [[pancreatic cancer]], [[surgery]] is the primary modality of treatment. However, surgery is performed only in a small fraction of patients who have resectable lesions. Majority of patients have unresectable disease and are treated with [[chemotherapy]] and/or [[radiation therapy]] as a part of [[adjuvant]] or [[neoadjuvant therapy]]. <nowiki/> Curative [[resection]] is not performed in cases of extrapancreatic involvement that require [[Palliative care|palliative therapy]]. As per the guidelines of The ''National Comprehensive Cancer Network (NCCN),'' patients with locally advanced unresectable or [[Metastasis|metastatic]] disease should be treated with a combination of [[Leucovorin]], 5-fuorouracil, [[Oxaliplatin]], and [[Irinotecan]] also known as [[FOLFIRINOX regimen]]. [[Neoadjuvant chemotherapy|Neoadjuvant]] therapy is preferred as shrinkage of the [[tumor]] using chemotherapy makes [[resection]] easier and improves patient prognosis. Radiotherapy may also form part of [[Neoadjuvant chemotherapy|neoadjuvant]] therapy to facilitate tumor shrinkage, but its use on unresectable [[Tumor|tumors]] remains controversial.


__NOTOC__
==Medical Therapy==
==Medical Therapy==
:*There are five different types of treatment for patients with pancreatic cancer.
*In patients with pancreatic cancer, [[surgery]] is the primary modality of treatment.
:**Surgery  
*Patients with unresectable disease are treated with [[chemotherapy]] and/or [[radiation therapy]] as a part of [[adjuvant]] or [[neoadjuvant therapy]].
:**Radiation therapy  
*Extrapancreatic disease requires [[Palliative care|palliative]] therapy and curative [[resection]] is not performed in such patients.
:**Chemotherapy  
*The different types of treatment modalities available for patients with [[pancreatic cancer]] are:
:**Chemoradiation therapy  
**[[Surgery]]
:**Targeted therapy
**[[Radiation therapy]]
**[[Chemotherapy]]
**Chemoradiation therapy  
**[[Targeted therapy]]


:*New types of treatment are being tested in clinical trials.  
*New types of treatment such as biologic therapy, are being studied in clinical trials.
:**Biologic therapy
===Chemotherapy guidelines ===


:* In patients with pancreatic cancer, surgery is the primary modality of treatment.
*The ''National Comprehensive Cancer Network (NCCN)'' has recommended guidelines for treatment in patients based on their performance status.
*In order to predict survival of patients in various stages of [[pancreatic cancer]], the performance status of a patient is a major [[Prognosis|prognostic]] factor.
*Patients with poor prognostic factors have poor performance status. This includes:<ref name="pmid22996141">{{cite journal |vauthors=Tas F, Sen F, Odabas H, Kılıc L, Keskın S, Yıldız I |title=Performance status of patients is the major prognostic factor at all stages of pancreatic cancer |journal=Int. J. Clin. Oncol. |volume=18 |issue=5 |pages=839–46 |year=2013 |pmid=22996141 |doi=10.1007/s10147-012-0474-9 |url=}}</ref>
**[[Metastasis|Metastatic disease]]
**Large [[tumor]]
**Severe [[weight loss]] 
**Preferred regimens based on performance status in locally advanced/metastatic disease are enlisted in the table as follows:<ref name="pmid23474363">{{cite journal |vauthors=Mukherjee S, Hurt CN, Bridgewater J, Falk S, Cummins S, Wasan H, Crosby T, Jephcott C, Roy R, Radhakrishna G, McDonald A, Ray R, Joseph G, Staffurth J, Abrams RA, Griffiths G, Maughan T |title=Gemcitabine-based or capecitabine-based chemoradiotherapy for locally advanced pancreatic cancer (SCALOP): a multicentre, randomised, phase 2 trial |journal=Lancet Oncol. |volume=14 |issue=4 |pages=317–26 |year=2013 |pmid=23474363 |pmc=3620899 |doi=10.1016/S1470-2045(13)70021-4 |url=}}</ref><ref name="pmid28376080">{{cite journal |vauthors=Hurt CN, Falk S, Crosby T, McDonald A, Ray R, Joseph G, Staffurth J, Abrams RA, Griffiths G, Maughan T, Mukherjee S |title=Long-term results and recurrence patterns from SCALOP: a phase II randomised trial of gemcitabine- or capecitabine-based chemoradiation for locally advanced pancreatic cancer |journal=Br. J. Cancer |volume=116 |issue=10 |pages=1264–1270 |year=2017 |pmid=28376080 |pmc=5482737 |doi=10.1038/bjc.2017.95 |url=}}</ref><ref name="pmid19307501">{{cite journal |vauthors=Huguet F, Girard N, Guerche CS, Hennequin C, Mornex F, Azria D |title=Chemoradiotherapy in the management of locally advanced pancreatic carcinoma: a qualitative systematic review |journal=J. Clin. Oncol. |volume=27 |issue=13 |pages=2269–77 |year=2009 |pmid=19307501 |doi=10.1200/JCO.2008.19.7921 |url=}}</ref><ref name="pmid7028759">{{cite journal |vauthors=Hazel JJ, Thirlwell MP, Huggins M, Maksymiuk A, MacFarlane JK |title=Multi-drug chemotherapy with and without radiation for carcinoma of the stomach and pancreas: a prospective randomized trial |journal=J Can Assoc Radiol |volume=32 |issue=3 |pages=164–5 |year=1981 |pmid=7028759 |doi= |url=}}</ref><ref name="pmid18467316">{{cite journal |vauthors=Chauffert B, Mornex F, Bonnetain F, Rougier P, Mariette C, Bouché O, Bosset JF, Aparicio T, Mineur L, Azzedine A, Hammel P, Butel J, Stremsdoerfer N, Maingon P, Bedenne L |title=Phase III trial comparing intensive induction chemoradiotherapy (60 Gy, infusional 5-FU and intermittent cisplatin) followed by maintenance gemcitabine with gemcitabine alone for locally advanced unresectable pancreatic cancer. Definitive results of the 2000-01 FFCD/SFRO study |journal=Ann. Oncol. |volume=19 |issue=9 |pages=1592–9 |year=2008 |pmid=18467316 |doi=10.1093/annonc/mdn281 |url=}}</ref><ref name="pmid28222309">{{cite journal |vauthors=Irigoyen A, Gallego J, Guillén Ponce C, Vera R, Iranzo V, Ales I, Arévalo S, Pisa A, Martín M, Salud A, Falcó E, Sáenz A, Manzano Mozo JL, Pulido G, Martínez Galán J, Pazo-Cid R, Rivera F, García García T, Serra O, Fernández Parra EM, Hurtado A, Gómez Reina MJ, López Gomez LJ, Martínez Ortega E, Benavides M, Aranda E |title=Gemcitabine-erlotinib versus gemcitabine-erlotinib-capecitabine in the first-line treatment of patients with metastatic pancreatic cancer: Efficacy and safety results of a phase IIb randomised study from the Spanish TTD Collaborative Group |journal=Eur. J. Cancer |volume=75 |issue= |pages=73–82 |year=2017 |pmid=28222309 |doi=10.1016/j.ejca.2016.12.032 |url=}}</ref><ref name="pmid17986845">{{cite journal |vauthors=Brasiūniene B, Juozaityte E |title=The effect of combined treatment methods on survival and toxicity in patients with pancreatic cancer |journal=Medicina (Kaunas) |volume=43 |issue=9 |pages=716–25 |year=2007 |pmid=17986845 |doi= |url=}}</ref><ref name="pmid28259610">{{cite journal |vauthors=Middleton G, Palmer DH, Greenhalf W, Ghaneh P, Jackson R, Cox T, Evans A, Shaw VE, Wadsley J, Valle JW, Propper D, Wasan H, Falk S, Cunningham D, Coxon F, Ross P, Madhusudan S, Wadd N, Corrie P, Hickish T, Costello E, Campbell F, Rawcliffe C, Neoptolemos JP |title=Vandetanib plus gemcitabine versus placebo plus gemcitabine in locally advanced or metastatic pancreatic carcinoma (ViP): a prospective, randomised, double-blind, multicentre phase 2 trial |journal=Lancet Oncol. |volume=18 |issue=4 |pages=486–499 |year=2017 |pmid=28259610 |doi=10.1016/S1470-2045(17)30084-0 |url=}}</ref><ref name="pmid28105634">{{cite journal |vauthors=Xia BT, Fu B, Wang J, Kim Y, Ahmad SA, Dhar VK, Levinsky NC, Hanseman DJ, Habib DA, Wilson GC, Smith M, Olowokure OO, Kharofa J, Al Humaidi AH, Choe KA, Abbott DE, Ahmad SA |title=Does radiologic response correlate to pathologic response in patients undergoing neoadjuvant therapy for borderline resectable pancreatic malignancy? |journal=J Surg Oncol |volume=115 |issue=4 |pages=376–383 |year=2017 |pmid=28105634 |doi=10.1002/jso.24538 |url=}}</ref><ref name="pmid27484349">{{cite journal |vauthors=Choi SJ, Kim HJ, Kim JS, Bak YT, Kim JS |title=Radiation recall gastritis secondary to combination of gemcitabine and erlotinib in pancreatic cancer and response to PPI - a case report |journal=BMC Cancer |volume=16 |issue= |pages=588 |year=2016 |pmid=27484349 |pmc=4971692 |doi=10.1186/s12885-016-2616-3 |url=}}</ref><ref name="pmid27358556">{{cite journal |vauthors=Wang Y, Hu GF, Zhang QQ, Tang N, Guo J, Liu LY, Han X, Wang X, Wang ZH |title=Efficacy and safety of gemcitabine plus erlotinib for locally advanced or metastatic pancreatic cancer: a systematic review and meta-analysis |journal=Drug Des Devel Ther |volume=10 |issue= |pages=1961–72 |year=2016 |pmid=27358556 |pmc=4912328 |doi=10.2147/DDDT.S105442 |url=}}</ref><ref name="pmid27139057">{{cite journal |vauthors=Hammel P, Huguet F, van Laethem JL, Goldstein D, Glimelius B, Artru P, Borbath I, Bouché O, Shannon J, André T, Mineur L, Chibaudel B, Bonnetain F, Louvet C |title=Effect of Chemoradiotherapy vs Chemotherapy on Survival in Patients With Locally Advanced Pancreatic Cancer Controlled After 4 Months of Gemcitabine With or Without Erlotinib: The LAP07 Randomized Clinical Trial |journal=JAMA |volume=315 |issue=17 |pages=1844–53 |year=2016 |pmid=27139057 |doi=10.1001/jama.2016.4324 |url=}}</ref><ref name="pmid26929778">{{cite journal |vauthors=Chen J, Kaley K, Garcon MC, Rodriguez T, Saif MW |title=A novel schedule of erlotinib/capecitabine (7/7) as salvage therapy in previously treated advanced pancreatic adenocarcinoma: a case series |journal=Therap Adv Gastroenterol |volume=9 |issue=2 |pages=162–8 |year=2016 |pmid=26929778 |pmc=4749861 |doi=10.1177/1756283X15622779 |url=}}</ref>
{| class="wikitable"
! colspan="2" style="background:#4479BA; color: #FFFFFF;" |PREFERRED REGIMENS BASED ON PERFORMANCE STATUS IN LOCALLY ADVANCED/METASTATIC DISEASE
|-
| style="background:#DCDCDC; + " |Good perfomance status
|[[FOLFIRINOX regimen|FOLFIRINOX]]<ref name="pmid21561347">{{cite journal |vauthors=Conroy T, Desseigne F, Ychou M, Bouché O, Guimbaud R, Bécouarn Y, Adenis A, Raoul JL, Gourgou-Bourgade S, de la Fouchardière C, Bennouna J, Bachet JB, Khemissa-Akouz F, Péré-Vergé D, Delbaldo C, Assenat E, Chauffert B, Michel P, Montoto-Grillot C, Ducreux M |title=FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer |journal=N. Engl. J. Med. |volume=364 |issue=19 |pages=1817–25 |year=2011 |pmid=21561347 |doi=10.1056/NEJMoa1011923 |url=}}</ref><ref name="pmid22964956">{{cite journal |vauthors=Peddi PF, Lubner S, McWilliams R, Tan BR, Picus J, Sorscher SM, Suresh R, Lockhart AC, Wang J, Menias C, Gao F, Linehan D, Wang-Gillam A |title=Multi-institutional experience with FOLFIRINOX in pancreatic adenocarcinoma |journal=JOP |volume=13 |issue=5 |pages=497–501 |year=2012 |pmid=22964956 |doi= |url=}}</ref><ref name="pmid25037971">{{cite journal |vauthors=Marthey L, Sa-Cunha A, Blanc JF, Gauthier M, Cueff A, Francois E, Trouilloud I, Malka D, Bachet JB, Coriat R, Terrebonne E, De La Fouchardière C, Manfredi S, Solub D, Lécaille C, Thirot Bidault A, Carbonnel F, Taieb J |title=FOLFIRINOX for locally advanced pancreatic adenocarcinoma: results of an AGEO multicenter prospective observational cohort |journal=Ann. Surg. Oncol. |volume=22 |issue=1 |pages=295–301 |year=2015 |pmid=25037971 |doi=10.1245/s10434-014-3898-9 |url=}}</ref><ref name="pmid25358667">{{cite journal |vauthors=Blazer M, Wu C, Goldberg RM, Phillips G, Schmidt C, Muscarella P, Wuthrick E, Williams TM, Reardon J, Ellison EC, Bloomston M, Bekaii-Saab T |title=Neoadjuvant modified (m) FOLFIRINOX for locally advanced unresectable (LAPC) and borderline resectable (BRPC) adenocarcinoma of the pancreas |journal=Ann. Surg. Oncol. |volume=22 |issue=4 |pages=1153–9 |year=2015 |pmid=25358667 |pmc=4373613 |doi=10.1245/s10434-014-4225-1 |url=}}</ref><ref name="pmid25599322">{{cite journal |vauthors=Ferrone CR, Marchegiani G, Hong TS, Ryan DP, Deshpande V, McDonnell EI, Sabbatino F, Santos DD, Allen JN, Blaszkowsky LS, Clark JW, Faris JE, Goyal L, Kwak EL, Murphy JE, Ting DT, Wo JY, Zhu AX, Warshaw AL, Lillemoe KD, Fernández-del Castillo C |title=Radiological and surgical implications of neoadjuvant treatment with FOLFIRINOX for locally advanced and borderline resectable pancreatic cancer |journal=Ann. Surg. |volume=261 |issue=1 |pages=12–7 |year=2015 |pmid=25599322 |pmc=4349683 |doi=10.1097/SLA.0000000000000867 |url=}}</ref><ref name="pmid25734581">{{cite journal |vauthors=Mellon EA, Hoffe SE, Springett GM, Frakes JM, Strom TJ, Hodul PJ, Malafa MP, Chuong MD, Shridhar R |title=Long-term outcomes of induction chemotherapy and neoadjuvant stereotactic body radiotherapy for borderline resectable and locally advanced pancreatic adenocarcinoma |journal=Acta Oncol |volume=54 |issue=7 |pages=979–85 |year=2015 |pmid=25734581 |doi=10.3109/0284186X.2015.1004367 |url=}}</ref><ref name="pmid26065868">{{cite journal |vauthors=Sadot E, Doussot A, O'Reilly EM, Lowery MA, Goodman KA, Do RK, Tang LH, Gönen M, D'Angelica MI, DeMatteo RP, Kingham TP, Jarnagin WR, Allen PJ |title=FOLFIRINOX Induction Therapy for Stage 3 Pancreatic Adenocarcinoma |journal=Ann. Surg. Oncol. |volume=22 |issue=11 |pages=3512–21 |year=2015 |pmid=26065868 |pmc=4849545 |doi=10.1245/s10434-015-4647-4 |url=}}</ref><ref name="pmid27022826">{{cite journal |vauthors=Stein SM, James ES, Deng Y, Cong X, Kortmansky JS, Li J, Staugaard C, Indukala D, Boustani AM, Patel V, Cha CH, Salem RR, Chang B, Hochster HS, Lacy J |title=Final analysis of a phase II study of modified FOLFIRINOX in locally advanced and metastatic pancreatic cancer |journal=Br. J. Cancer |volume=114 |issue=7 |pages=737–43 |year=2016 |pmid=27022826 |pmc=4984865 |doi=10.1038/bjc.2016.45 |url=}}</ref><ref name="pmid27160474">{{cite journal |vauthors=Suker M, Beumer BR, Sadot E, Marthey L, Faris JE, Mellon EA, El-Rayes BF, Wang-Gillam A, Lacy J, Hosein PJ, Moorcraft SY, Conroy T, Hohla F, Allen P, Taieb J, Hong TS, Shridhar R, Chau I, van Eijck CH, Koerkamp BG |title=FOLFIRINOX for locally advanced pancreatic cancer: a systematic review and patient-level meta-analysis |journal=Lancet Oncol. |volume=17 |issue=6 |pages=801–810 |year=2016 |pmid=27160474 |pmc=5527756 |doi=10.1016/S1470-2045(16)00172-8 |url=}}</ref>
|-
| style="background:#DCDCDC; + " |Good perfomance status with intolerance to [[FOLFIRINOX regimen|FOLFIRINOX]]
|[[Paclitaxel]] protein bound '''AND''' [[Gemcitabine]]
|-
| style="background:#DCDCDC; + " | Poor performance status
|[[Gemcitabine]] monotherapy<ref name="pmid15908661">{{cite journal |vauthors=Louvet C, Labianca R, Hammel P, Lledo G, Zampino MG, André T, Zaniboni A, Ducreux M, Aitini E, Taïeb J, Faroux R, Lepere C, de Gramont A |title=Gemcitabine in combination with oxaliplatin compared with gemcitabine alone in locally advanced or metastatic pancreatic cancer: results of a GERCOR and GISCAD phase III trial |journal=J. Clin. Oncol. |volume=23 |issue=15 |pages=3509–16 |year=2005 |pmid=15908661 |doi=10.1200/JCO.2005.06.023 |url=}}</ref><ref name="pmid15084616">{{cite journal |vauthors=Van Cutsem E, van de Velde H, Karasek P, Oettle H, Vervenne WL, Szawlowski A, Schoffski P, Post S, Verslype C, Neumann H, Safran H, Humblet Y, Perez Ruixo J, Ma Y, Von Hoff D |title=Phase III trial of gemcitabine plus tipifarnib compared with gemcitabine plus placebo in advanced pancreatic cancer |journal=J. Clin. Oncol. |volume=22 |issue=8 |pages=1430–8 |year=2004 |pmid=15084616 |doi=10.1200/JCO.2004.10.112 |url=}}</ref><ref name="pmid15365074">{{cite journal |vauthors=Rocha Lima CM, Green MR, Rotche R, Miller WH, Jeffrey GM, Cisar LA, Morganti A, Orlando N, Gruia G, Miller LL |title=Irinotecan plus gemcitabine results in no survival advantage compared with gemcitabine monotherapy in patients with locally advanced or metastatic pancreatic cancer despite increased tumor response rate |journal=J. Clin. Oncol. |volume=22 |issue=18 |pages=3776–83 |year=2004 |pmid=15365074 |doi=10.1200/JCO.2004.12.082 |url=}}</ref><ref name="pmid20185458">{{cite journal |vauthors=Ishii H, Furuse J, Boku N, Okusaka T, Ikeda M, Ohkawa S, Fukutomi A, Hamamoto Y, Nakamura K, Fukuda H |title=Phase II study of gemcitabine chemotherapy alone for locally advanced pancreatic carcinoma: JCOG0506 |journal=Jpn. J. Clin. Oncol. |volume=40 |issue=6 |pages=573–9 |year=2010 |pmid=20185458 |doi=10.1093/jjco/hyq011 |url=}}</ref>
|-
| style="background:#DCDCDC; + " | Poor performance status  refractory to [[Gemcitabine]]
|[[Capecitabine]] '''OR''' [[capecitabine]] '''AND''' [[erlotinib]]<ref name="pmid17947726">{{cite journal |vauthors=Kulke MH, Blaszkowsky LS, Ryan DP, Clark JW, Meyerhardt JA, Zhu AX, Enzinger PC, Kwak EL, Muzikansky A, Lawrence C, Fuchs CS |title=Capecitabine plus erlotinib in gemcitabine-refractory advanced pancreatic cancer |journal=J. Clin. Oncol. |volume=25 |issue=30 |pages=4787–92 |year=2007 |pmid=17947726 |doi=10.1200/JCO.2007.11.8521 |url=}}</ref>
|}


:* Extrapancreatic disease requires palliative therapy and curative resection is not performed in such patients.
===Preferred regimens based on the stage of pancreatic cancer:===
:* Patients with unresectable disease are treated with chemotherapy and/or radiation therapy as a part of adjuvant or neoadjuvant therapy.
'''''Stages I-II:'''''
:* Curative resection is not contraindicated in all patients with vascular invasion.<ref name="pmid17632763">{{cite journal |vauthors=Al-Haddad M, Martin JK, Nguyen J, Pungpapong S, Raimondo M, Woodward T, Kim G, Noh K, Wallace MB |title=Vascular resection and reconstruction for pancreatic malignancy: a single center survival study |journal=J. Gastrointest. Surg. |volume=11 |issue=9 |pages=1168–74 |year=2007 |pmid=17632763 |doi=10.1007/s11605-007-0216-x |url=}}</ref><ref name="pmid21768431">{{cite journal |vauthors=Donahue TR, Isacoff WH, Hines OJ, Tomlinson JS, Farrell JJ, Bhat YM, Garon E, Clerkin B, Reber HA |title=Downstaging chemotherapy and alteration in the classic computed tomography/magnetic resonance imaging signs of vascular involvement in patients with pancreaticobiliary malignant tumors: influence on patient selection for surgery |journal=Arch Surg |volume=146 |issue=7 |pages=836–43 |year=2011 |pmid=21768431 |doi=10.1001/archsurg.2011.152 |url=}}</ref><ref name="pmid15585381">{{cite journal |vauthors=Tseng JF, Raut CP, Lee JE, Pisters PW, Vauthey JN, Abdalla EK, Gomez HF, Sun CC, Crane CH, Wolff RA, Evans DB |title=Pancreaticoduodenectomy with vascular resection: margin status and survival duration |journal=J. Gastrointest. Surg. |volume=8 |issue=8 |pages=935–49; discussion 949–50 |year=2004 |pmid=15585381 |doi=10.1016/j.gassur.2004.09.046 |url=}}</ref><ref name="pmid19221327">{{cite journal |vauthors=Martin RC, Scoggins CR, Egnatashvili V, Staley CA, McMasters KM, Kooby DA |title=Arterial and venous resection for pancreatic adenocarcinoma: operative and long-term outcomes |journal=Arch Surg |volume=144 |issue=2 |pages=154–9 |year=2009 |pmid=19221327 |doi=10.1001/archsurg.2008.547 |url=}}</ref><ref name="pmid22932857">{{cite journal |vauthors=Castleberry AW, White RR, De La Fuente SG, Clary BM, Blazer DG, McCann RL, Pappas TN, Tyler DS, Scarborough JE |title=The impact of vascular resection on early postoperative outcomes after pancreaticoduodenectomy: an analysis of the American College of Surgeons National Surgical Quality Improvement Program database |journal=Ann. Surg. Oncol. |volume=19 |issue=13 |pages=4068–77 |year=2012 |pmid=22932857 |doi=10.1245/s10434-012-2585-y |url=}}</ref>
:** Involvement of the portal or superior mesenteric vein can be resected and reconstructed with the help of splenic, saphenous or internal jugular veins.<ref name="pmid9635805">{{cite journal |vauthors=Leach SD, Lee JE, Charnsangavej C, Cleary KR, Lowy AM, Fenoglio CJ, Pisters PW, Evans DB |title=Survival following pancreaticoduodenectomy with resection of the superior mesenteric-portal vein confluence for adenocarcinoma of the pancreatic head |journal=Br J Surg |volume=85 |issue=5 |pages=611–7 |year=1998 |pmid=9635805 |doi=10.1046/j.1365-2168.1998.00641.x |url=}}</ref><ref name="pmid8597509">{{cite journal |vauthors=Fuhrman GM, Leach SD, Staley CA, Cusack JC, Charnsangavej C, Cleary KR, El-Naggar AK, Fenoglio CJ, Lee JE, Evans DB |title=Rationale for en bloc vein resection in the treatment of pancreatic adenocarcinoma adherent to the superior mesenteric-portal vein confluence. Pancreatic Tumor Study Group |journal=Ann. Surg. |volume=223 |issue=2 |pages=154–62 |year=1996 |pmid=8597509 |pmc=1235091 |doi= |url=}}</ref><ref name="pmid22886567">{{cite journal |vauthors=Murakami Y, Uemura K, Sudo T, Hashimoto Y, Nakashima A, Kondo N, Nakagawa N, Sueda T |title=Benefit of portal or superior mesenteric vein resection with adjuvant chemotherapy for patients with pancreatic head carcinoma |journal=J Surg Oncol |volume=107 |issue=4 |pages=414–21 |year=2013 |pmid=22886567 |doi=10.1002/jso.23229 |url=}}</ref><ref name="pmid19156463">{{cite journal |vauthors=Ramacciato G, Mercantini P, Petrucciani N, Giaccaglia V, Nigri G, Ravaioli M, Cescon M, Cucchetti A, Del Gaudio M |title=Does portal-superior mesenteric vein invasion still indicate irresectability for pancreatic carcinoma? |journal=Ann. Surg. Oncol. |volume=16 |issue=4 |pages=817–25 |year=2009 |pmid=19156463 |doi=10.1245/s10434-008-0281-8 |url=}}</ref>
:** The involvement of arteries such as the hepatic, celiac or superior mesenteric are contraindications to resection.<ref name="pmid22064622">{{cite journal |vauthors=Mollberg N, Rahbari NN, Koch M, Hartwig W, Hoeger Y, Büchler MW, Weitz J |title=Arterial resection during pancreatectomy for pancreatic cancer: a systematic review and meta-analysis |journal=Ann. Surg. |volume=254 |issue=6 |pages=882–93 |year=2011 |pmid=22064622 |doi=10.1097/SLA.0b013e31823ac299 |url=}}</ref>
:* Various methods of surgical resection may be employed and each of these has its own sets of risks and perioperative complications. The facts are discussed by the patient and surgical team before arriving at a well-informed decision. The method of surgical resection depends on the following features:<ref name="pmid25207767">{{cite journal |vauthors=Ryan DP, Hong TS, Bardeesy N |title=Pancreatic adenocarcinoma |journal=N. Engl. J. Med. |volume=371 |issue=11 |pages=1039–49 |year=2014 |pmid=25207767 |doi=10.1056/NEJMra1404198 |url=}}</ref><ref name="pmid27163957">{{cite journal |vauthors=Allen PJ, Kuk D, Castillo CF, Basturk O, Wolfgang CL, Cameron JL, Lillemoe KD, Ferrone CR, Morales-Oyarvide V, He J, Weiss MJ, Hruban RH, Gönen M, Klimstra DS, Mino-Kenudson M |title=Multi-institutional Validation Study of the American Joint Commission on Cancer (8th Edition) Changes for T and N Staging in Patients With Pancreatic Adenocarcinoma |journal=Ann. Surg. |volume=265 |issue=1 |pages=185–191 |year=2017 |pmid=27163957 |doi=10.1097/SLA.0000000000001763 |url=}}</ref><ref name="pmid17580363">{{cite journal |vauthors=Bilimoria KY, Bentrem DJ, Ko CY, Ritchey J, Stewart AK, Winchester DP, Talamonti MS |title=Validation of the 6th edition AJCC Pancreatic Cancer Staging System: report from the National Cancer Database |journal=Cancer |volume=110 |issue=4 |pages=738–44 |year=2007 |pmid=17580363 |doi=10.1002/cncr.22852 |url=}}</ref>
:** Locally invasive characteristics of the neoplasm
:** Size
:* Surgical methods of curative resection include:
:** Distal Pancreatectomy
:** Total pancreatectomy
:**Pancreaticoduodenectomy, where pylorus may or may not be spared on an individual basis.
:*The National Comprehensive Cancer Network (NCCN) has recommended certain guidelines on resectability of pancreatic neoplasms based on a statement passed by the American pancreatic association:<ref name="pmid28948329">{{cite journal |vauthors=Fonseca AL, Fleming JB |title=Surgery for pancreatic cancer: critical radiologic findings for clinical decision making |journal=Abdom Radiol (NY) |volume= |issue= |pages= |year=2017 |pmid=28948329 |doi=10.1007/s00261-017-1332-z |url=}}</ref><ref name="pmid24354378">{{cite journal |vauthors=Al-Hawary MM, Francis IR, Chari ST, Fishman EK, Hough DM, Lu DS, Macari M, Megibow AJ, Miller FH, Mortele KJ, Merchant NB, Minter RM, Tamm EP, Sahani DV, Simeone DM |title=Pancreatic ductal adenocarcinoma radiology reporting template: consensus statement of the Society of Abdominal Radiology and the American Pancreatic Association |journal=Radiology |volume=270 |issue=1 |pages=248–60 |year=2014 |pmid=24354378 |doi=10.1148/radiol.13131184 |url=}}</ref><ref name="pmid27247221">{{cite journal |vauthors=Khorana AA, Mangu PB, Berlin J, Engebretson A, Hong TS, Maitra A, Mohile SG, Mumber M, Schulick R, Shapiro M, Urba S, Zeh HJ, Katz MH |title=Potentially Curable Pancreatic Cancer: American Society of Clinical Oncology Clinical Practice Guideline |journal=J. Clin. Oncol. |volume=34 |issue=21 |pages=2541–56 |year=2016 |pmid=27247221 |doi=10.1200/JCO.2016.67.5553 |url=}}</ref><ref name="pmid23532000">{{cite journal |vauthors=Yamada S, Fujii T, Sugimoto H, Nomoto S, Takeda S, Kodera Y, Nakao A |title=Aggressive surgery for borderline resectable pancreatic cancer: evaluation of National Comprehensive Cancer Network guidelines |journal=Pancreas |volume=42 |issue=6 |pages=1004–10 |year=2013 |pmid=23532000 |doi=10.1097/MPA.0b013e31827b2d7c |url=}}</ref><ref name="pmid27247216">{{cite journal |vauthors=Balaban EP, Mangu PB, Khorana AA, Shah MA, Mukherjee S, Crane CH, Javle MM, Eads JR, Allen P, Ko AH, Engebretson A, Herman JM, Strickler JH, Benson AB, Urba S, Yee NS |title=Locally Advanced, Unresectable Pancreatic Cancer: American Society of Clinical Oncology Clinical Practice Guideline |journal=J. Clin. Oncol. |volume=34 |issue=22 |pages=2654–68 |year=2016 |pmid=27247216 |doi=10.1200/JCO.2016.67.5561 |url=}}</ref>
:*Patient selection is based on:
:**Resection margins
:**High probability of cure
:**Patient's age
:**Comorbidities
:*The European Society for Medical Oncology (ESMO) has certain guidelines on the treatment of metastatic pancreatic cancer:<ref name="pmid26314780">{{cite journal |vauthors=Ducreux M, Cuhna AS, Caramella C, Hollebecque A, Burtin P, Goéré D, Seufferlein T, Haustermans K, Van Laethem JL, Conroy T, Arnold D |title=Cancer of the pancreas: ESMO Clinical Practice Guidelines for diagnosis, treatment, and follow-up |journal=Ann. Oncol. |volume=26 Suppl 5 |issue= |pages=v56–68 |year=2015 |pmid=26314780 |doi=10.1093/annonc/mdv295 |url=}}</ref><ref name="pmid22997452">{{cite journal |vauthors=Seufferlein T, Bachet JB, Van Cutsem E, Rougier P |title=Pancreatic adenocarcinoma: ESMO-ESDO Clinical Practice Guidelines for diagnosis, treatment and follow-up |journal=Ann. Oncol. |volume=23 Suppl 7 |issue= |pages=vii33–40 |year=2012 |pmid=22997452 |doi=10.1093/annonc/mds224 |url=}}</ref><ref name="pmid26122369">{{cite journal |vauthors=Evans DB, George B, Tsai S |title=Non-metastatic Pancreatic Cancer: Resectable, Borderline Resectable, and Locally Advanced-Definitions of Increasing Importance for the Optimal Delivery of Multimodality Therapy |journal=Ann. Surg. Oncol. |volume=22 |issue=11 |pages=3409–13 |year=2015 |pmid=26122369 |doi=10.1245/s10434-015-4649-2 |url=}}</ref>
:**Chemotherapy not preferred.
:**Gemcitabine is preferred over 5 FU.
:**Treatment is symptomatic with bypass surgery or stent placement for gastric outlet obstruction or obstructive jaundice.
:*In case of locally advanced disease which is unresectable, the following methods of treatment are preferred:<ref name="pmid25524417">{{cite journal |vauthors=Rombouts SJ, Vogel JA, van Santvoort HC, van Lienden KP, van Hillegersberg R, Busch OR, Besselink MG, Molenaar IQ |title=Systematic review of innovative ablative therapies for the treatment of locally advanced pancreatic cancer |journal=Br J Surg |volume=102 |issue=3 |pages=182–93 |year=2015 |pmid=25524417 |doi=10.1002/bjs.9716 |url=}}</ref><ref name="pmid25524417" />
:**Microwave ablation
:**Photodynamic therapy
:**Irreversible electroporation
:**Photodynamic therapy
:**High-intensity focused ultrasound (HIFU)
:**Iodine-125–cryosurgery
:**Iodine-125
:**Stereotactic body radiation therapy (SBRT)
:**Radiofrequency ablation (RFA)
===Chemotherapy ===


:*The National Comprehensive Cancer Network (NCCN) has recommended guidelines for treatment in patients based on their performance status.
''Neoadjuvant therapy<sup> </sup>:''
:*In order to predict survival of patients in various stages of pancreatic cancer, the performance status of a patient is a major prognostic factor.
*There are no standard regimens currently for [[Neoadjuvant|neoadjuvant treatment]] of resectable [[pancreatic cancer]].
:*Patients with poor prognostic factors have poor performance status. This includes:<ref name="pmid22996141">{{cite journal |vauthors=Tas F, Sen F, Odabas H, Kılıc L, Keskın S, Yıldız I |title=Performance status of patients is the major prognostic factor at all stages of pancreatic cancer |journal=Int. J. Clin. Oncol. |volume=18 |issue=5 |pages=839–46 |year=2013 |pmid=22996141 |doi=10.1007/s10147-012-0474-9 |url=}}</ref>
*Preferred [[Neoadjuvant|neoadjuvant drug regimens]] are as follows:
:**Metastatic disease
**[[Capecitabine]]
:**Large tumor
**[[Fluorouracil]]
:**Severe weight loss
**[[Fluorouracil]] or [[Cisplatin]] plus [[Radiation therapy|radiation]]
:*Therapy proposed for patients based on the resectability of disease and performance status is as follows:<ref name="pmid17986845">{{cite journal |vauthors=Brasiūniene B, Juozaityte E |title=The effect of combined treatment methods on survival and toxicity in patients with pancreatic cancer |journal=Medicina (Kaunas) |volume=43 |issue=9 |pages=716–25 |year=2007 |pmid=17986845 |doi= |url=}}</ref><ref name="pmid23474363">{{cite journal |vauthors=Mukherjee S, Hurt CN, Bridgewater J, Falk S, Cummins S, Wasan H, Crosby T, Jephcott C, Roy R, Radhakrishna G, McDonald A, Ray R, Joseph G, Staffurth J, Abrams RA, Griffiths G, Maughan T |title=Gemcitabine-based or capecitabine-based chemoradiotherapy for locally advanced pancreatic cancer (SCALOP): a multicentre, randomised, phase 2 trial |journal=Lancet Oncol. |volume=14 |issue=4 |pages=317–26 |year=2013 |pmid=23474363 |pmc=3620899 |doi=10.1016/S1470-2045(13)70021-4 |url=}}</ref><ref name="pmid28376080">{{cite journal |vauthors=Hurt CN, Falk S, Crosby T, McDonald A, Ray R, Joseph G, Staffurth J, Abrams RA, Griffiths G, Maughan T, Mukherjee S |title=Long-term results and recurrence patterns from SCALOP: a phase II randomised trial of gemcitabine- or capecitabine-based chemoradiation for locally advanced pancreatic cancer |journal=Br. J. Cancer |volume=116 |issue=10 |pages=1264–1270 |year=2017 |pmid=28376080 |pmc=5482737 |doi=10.1038/bjc.2017.95 |url=}}</ref><ref name="pmid19307501">{{cite journal |vauthors=Huguet F, Girard N, Guerche CS, Hennequin C, Mornex F, Azria D |title=Chemoradiotherapy in the management of locally advanced pancreatic carcinoma: a qualitative systematic review |journal=J. Clin. Oncol. |volume=27 |issue=13 |pages=2269–77 |year=2009 |pmid=19307501 |doi=10.1200/JCO.2008.19.7921 |url=}}</ref><ref name="pmid7028759">{{cite journal |vauthors=Hazel JJ, Thirlwell MP, Huggins M, Maksymiuk A, MacFarlane JK |title=Multi-drug chemotherapy with and without radiation for carcinoma of the stomach and pancreas: a prospective randomized trial |journal=J Can Assoc Radiol |volume=32 |issue=3 |pages=164–5 |year=1981 |pmid=7028759 |doi= |url=}}</ref><ref name="pmid18467316">{{cite journal |vauthors=Chauffert B, Mornex F, Bonnetain F, Rougier P, Mariette C, Bouché O, Bosset JF, Aparicio T, Mineur L, Azzedine A, Hammel P, Butel J, Stremsdoerfer N, Maingon P, Bedenne L |title=Phase III trial comparing intensive induction chemoradiotherapy (60 Gy, infusional 5-FU and intermittent cisplatin) followed by maintenance gemcitabine with gemcitabine alone for locally advanced unresectable pancreatic cancer. Definitive results of the 2000-01 FFCD/SFRO study |journal=Ann. Oncol. |volume=19 |issue=9 |pages=1592–9 |year=2008 |pmid=18467316 |doi=10.1093/annonc/mdn281 |url=}}</ref><ref name="pmid28222309">{{cite journal |vauthors=Irigoyen A, Gallego J, Guillén Ponce C, Vera R, Iranzo V, Ales I, Arévalo S, Pisa A, Martín M, Salud A, Falcó E, Sáenz A, Manzano Mozo JL, Pulido G, Martínez Galán J, Pazo-Cid R, Rivera F, García García T, Serra O, Fernández Parra EM, Hurtado A, Gómez Reina MJ, López Gomez LJ, Martínez Ortega E, Benavides M, Aranda E |title=Gemcitabine-erlotinib versus gemcitabine-erlotinib-capecitabine in the first-line treatment of patients with metastatic pancreatic cancer: Efficacy and safety results of a phase IIb randomised study from the Spanish TTD Collaborative Group |journal=Eur. J. Cancer |volume=75 |issue= |pages=73–82 |year=2017 |pmid=28222309 |doi=10.1016/j.ejca.2016.12.032 |url=}}</ref><ref name="pmid28259610">{{cite journal |vauthors=Middleton G, Palmer DH, Greenhalf W, Ghaneh P, Jackson R, Cox T, Evans A, Shaw VE, Wadsley J, Valle JW, Propper D, Wasan H, Falk S, Cunningham D, Coxon F, Ross P, Madhusudan S, Wadd N, Corrie P, Hickish T, Costello E, Campbell F, Rawcliffe C, Neoptolemos JP |title=Vandetanib plus gemcitabine versus placebo plus gemcitabine in locally advanced or metastatic pancreatic carcinoma (ViP): a prospective, randomised, double-blind, multicentre phase 2 trial |journal=Lancet Oncol. |volume=18 |issue=4 |pages=486–499 |year=2017 |pmid=28259610 |doi=10.1016/S1470-2045(17)30084-0 |url=}}</ref><ref name="pmid28105634">{{cite journal |vauthors=Xia BT, Fu B, Wang J, Kim Y, Ahmad SA, Dhar VK, Levinsky NC, Hanseman DJ, Habib DA, Wilson GC, Smith M, Olowokure OO, Kharofa J, Al Humaidi AH, Choe KA, Abbott DE, Ahmad SA |title=Does radiologic response correlate to pathologic response in patients undergoing neoadjuvant therapy for borderline resectable pancreatic malignancy? |journal=J Surg Oncol |volume=115 |issue=4 |pages=376–383 |year=2017 |pmid=28105634 |doi=10.1002/jso.24538 |url=}}</ref><ref name="pmid27484349">{{cite journal |vauthors=Choi SJ, Kim HJ, Kim JS, Bak YT, Kim JS |title=Radiation recall gastritis secondary to combination of gemcitabine and erlotinib in pancreatic cancer and response to PPI - a case report |journal=BMC Cancer |volume=16 |issue= |pages=588 |year=2016 |pmid=27484349 |pmc=4971692 |doi=10.1186/s12885-016-2616-3 |url=}}</ref><ref name="pmid27358556">{{cite journal |vauthors=Wang Y, Hu GF, Zhang QQ, Tang N, Guo J, Liu LY, Han X, Wang X, Wang ZH |title=Efficacy and safety of gemcitabine plus erlotinib for locally advanced or metastatic pancreatic cancer: a systematic review and meta-analysis |journal=Drug Des Devel Ther |volume=10 |issue= |pages=1961–72 |year=2016 |pmid=27358556 |pmc=4912328 |doi=10.2147/DDDT.S105442 |url=}}</ref><ref name="pmid27139057">{{cite journal |vauthors=Hammel P, Huguet F, van Laethem JL, Goldstein D, Glimelius B, Artru P, Borbath I, Bouché O, Shannon J, André T, Mineur L, Chibaudel B, Bonnetain F, Louvet C |title=Effect of Chemoradiotherapy vs Chemotherapy on Survival in Patients With Locally Advanced Pancreatic Cancer Controlled After 4 Months of Gemcitabine With or Without Erlotinib: The LAP07 Randomized Clinical Trial |journal=JAMA |volume=315 |issue=17 |pages=1844–53 |year=2016 |pmid=27139057 |doi=10.1001/jama.2016.4324 |url=}}</ref><ref name="pmid26929778">{{cite journal |vauthors=Chen J, Kaley K, Garcon MC, Rodriguez T, Saif MW |title=A novel schedule of erlotinib/capecitabine (7/7) as salvage therapy in previously treated advanced pancreatic adenocarcinoma: a case series |journal=Therap Adv Gastroenterol |volume=9 |issue=2 |pages=162–8 |year=2016 |pmid=26929778 |pmc=4749861 |doi=10.1177/1756283X15622779 |url=}}</ref>
**[[Gemcitabine]] or [[Gemcitabine]] or [[Cisplatin]]
:**In patients with locally advanced unresectable or metastatic disease with good performance status:
''Adjuvant chemotherapy:''
:***Preferred treatment: FOLFIRINOX<ref name="pmid21561347">{{cite journal |vauthors=Conroy T, Desseigne F, Ychou M, Bouché O, Guimbaud R, Bécouarn Y, Adenis A, Raoul JL, Gourgou-Bourgade S, de la Fouchardière C, Bennouna J, Bachet JB, Khemissa-Akouz F, Péré-Vergé D, Delbaldo C, Assenat E, Chauffert B, Michel P, Montoto-Grillot C, Ducreux M |title=FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer |journal=N. Engl. J. Med. |volume=364 |issue=19 |pages=1817–25 |year=2011 |pmid=21561347 |doi=10.1056/NEJMoa1011923 |url=}}</ref><ref name="pmid22964956">{{cite journal |vauthors=Peddi PF, Lubner S, McWilliams R, Tan BR, Picus J, Sorscher SM, Suresh R, Lockhart AC, Wang J, Menias C, Gao F, Linehan D, Wang-Gillam A |title=Multi-institutional experience with FOLFIRINOX in pancreatic adenocarcinoma |journal=JOP |volume=13 |issue=5 |pages=497–501 |year=2012 |pmid=22964956 |doi= |url=}}</ref><ref name="pmid25037971">{{cite journal |vauthors=Marthey L, Sa-Cunha A, Blanc JF, Gauthier M, Cueff A, Francois E, Trouilloud I, Malka D, Bachet JB, Coriat R, Terrebonne E, De La Fouchardière C, Manfredi S, Solub D, Lécaille C, Thirot Bidault A, Carbonnel F, Taieb J |title=FOLFIRINOX for locally advanced pancreatic adenocarcinoma: results of an AGEO multicenter prospective observational cohort |journal=Ann. Surg. Oncol. |volume=22 |issue=1 |pages=295–301 |year=2015 |pmid=25037971 |doi=10.1245/s10434-014-3898-9 |url=}}</ref><ref name="pmid25358667">{{cite journal |vauthors=Blazer M, Wu C, Goldberg RM, Phillips G, Schmidt C, Muscarella P, Wuthrick E, Williams TM, Reardon J, Ellison EC, Bloomston M, Bekaii-Saab T |title=Neoadjuvant modified (m) FOLFIRINOX for locally advanced unresectable (LAPC) and borderline resectable (BRPC) adenocarcinoma of the pancreas |journal=Ann. Surg. Oncol. |volume=22 |issue=4 |pages=1153–9 |year=2015 |pmid=25358667 |pmc=4373613 |doi=10.1245/s10434-014-4225-1 |url=}}</ref><ref name="pmid25599322">{{cite journal |vauthors=Ferrone CR, Marchegiani G, Hong TS, Ryan DP, Deshpande V, McDonnell EI, Sabbatino F, Santos DD, Allen JN, Blaszkowsky LS, Clark JW, Faris JE, Goyal L, Kwak EL, Murphy JE, Ting DT, Wo JY, Zhu AX, Warshaw AL, Lillemoe KD, Fernández-del Castillo C |title=Radiological and surgical implications of neoadjuvant treatment with FOLFIRINOX for locally advanced and borderline resectable pancreatic cancer |journal=Ann. Surg. |volume=261 |issue=1 |pages=12–7 |year=2015 |pmid=25599322 |pmc=4349683 |doi=10.1097/SLA.0000000000000867 |url=}}</ref><ref name="pmid25734581">{{cite journal |vauthors=Mellon EA, Hoffe SE, Springett GM, Frakes JM, Strom TJ, Hodul PJ, Malafa MP, Chuong MD, Shridhar R |title=Long-term outcomes of induction chemotherapy and neoadjuvant stereotactic body radiotherapy for borderline resectable and locally advanced pancreatic adenocarcinoma |journal=Acta Oncol |volume=54 |issue=7 |pages=979–85 |year=2015 |pmid=25734581 |doi=10.3109/0284186X.2015.1004367 |url=}}</ref><ref name="pmid26065868">{{cite journal |vauthors=Sadot E, Doussot A, O'Reilly EM, Lowery MA, Goodman KA, Do RK, Tang LH, Gönen M, D'Angelica MI, DeMatteo RP, Kingham TP, Jarnagin WR, Allen PJ |title=FOLFIRINOX Induction Therapy for Stage 3 Pancreatic Adenocarcinoma |journal=Ann. Surg. Oncol. |volume=22 |issue=11 |pages=3512–21 |year=2015 |pmid=26065868 |pmc=4849545 |doi=10.1245/s10434-015-4647-4 |url=}}</ref><ref name="pmid27022826">{{cite journal |vauthors=Stein SM, James ES, Deng Y, Cong X, Kortmansky JS, Li J, Staugaard C, Indukala D, Boustani AM, Patel V, Cha CH, Salem RR, Chang B, Hochster HS, Lacy J |title=Final analysis of a phase II study of modified FOLFIRINOX in locally advanced and metastatic pancreatic cancer |journal=Br. J. Cancer |volume=114 |issue=7 |pages=737–43 |year=2016 |pmid=27022826 |pmc=4984865 |doi=10.1038/bjc.2016.45 |url=}}</ref><ref name="pmid27160474">{{cite journal |vauthors=Suker M, Beumer BR, Sadot E, Marthey L, Faris JE, Mellon EA, El-Rayes BF, Wang-Gillam A, Lacy J, Hosein PJ, Moorcraft SY, Conroy T, Hohla F, Allen P, Taieb J, Hong TS, Shridhar R, Chau I, van Eijck CH, Koerkamp BG |title=FOLFIRINOX for locally advanced pancreatic cancer: a systematic review and patient-level meta-analysis |journal=Lancet Oncol. |volume=17 |issue=6 |pages=801–810 |year=2016 |pmid=27160474 |pmc=5527756 |doi=10.1016/S1470-2045(16)00172-8 |url=}}</ref><ref name="pmid27160474" /><ref name="pmid25599322" /><ref name="pmid27160474" />
*In patients with resectable [[pancreatic cancer]]:
:**In patients with locally advanced unresectable or metastatic disease with good performance status with intolerance to FOLFIRINOX:
*Preferred regimen: [[Gemcitabine]] 1000 mg/m <sup>2</sup> IV q30min for 3 weeks; every 4 weeks for six cycles
:***Preferred treatment: Paclitaxel protein bound+ Gemcitabine
''Adjuvant chemotherapy and chemoradiation:''
:**In patients with locally advanced unresectable or metastatic disease with poor performance status:
:***Preferred treatment: Gemcitabine monotherapy<ref name="pmid15908661">{{cite journal |vauthors=Louvet C, Labianca R, Hammel P, Lledo G, Zampino MG, André T, Zaniboni A, Ducreux M, Aitini E, Taïeb J, Faroux R, Lepere C, de Gramont A |title=Gemcitabine in combination with oxaliplatin compared with gemcitabine alone in locally advanced or metastatic pancreatic cancer: results of a GERCOR and GISCAD phase III trial |journal=J. Clin. Oncol. |volume=23 |issue=15 |pages=3509–16 |year=2005 |pmid=15908661 |doi=10.1200/JCO.2005.06.023 |url=}}</ref><ref name="pmid15084616">{{cite journal |vauthors=Van Cutsem E, van de Velde H, Karasek P, Oettle H, Vervenne WL, Szawlowski A, Schoffski P, Post S, Verslype C, Neumann H, Safran H, Humblet Y, Perez Ruixo J, Ma Y, Von Hoff D |title=Phase III trial of gemcitabine plus tipifarnib compared with gemcitabine plus placebo in advanced pancreatic cancer |journal=J. Clin. Oncol. |volume=22 |issue=8 |pages=1430–8 |year=2004 |pmid=15084616 |doi=10.1200/JCO.2004.10.112 |url=}}</ref><ref name="pmid15365074">{{cite journal |vauthors=Rocha Lima CM, Green MR, Rotche R, Miller WH, Jeffrey GM, Cisar LA, Morganti A, Orlando N, Gruia G, Miller LL |title=Irinotecan plus gemcitabine results in no survival advantage compared with gemcitabine monotherapy in patients with locally advanced or metastatic pancreatic cancer despite increased tumor response rate |journal=J. Clin. Oncol. |volume=22 |issue=18 |pages=3776–83 |year=2004 |pmid=15365074 |doi=10.1200/JCO.2004.12.082 |url=}}</ref><ref name="pmid20185458">{{cite journal |vauthors=Ishii H, Furuse J, Boku N, Okusaka T, Ikeda M, Ohkawa S, Fukutomi A, Hamamoto Y, Nakamura K, Fukuda H |title=Phase II study of gemcitabine chemotherapy alone for locally advanced pancreatic carcinoma: JCOG0506 |journal=Jpn. J. Clin. Oncol. |volume=40 |issue=6 |pages=573–9 |year=2010 |pmid=20185458 |doi=10.1093/jjco/hyq011 |url=}}</ref>
:**In patients with locally advanced unresectable or metastatic disease with poor performance status refractory to Gemcitabine:
:***Preferred treatment: Capecitabine or capecitabine+erlotinib<ref name="pmid17947726">{{cite journal |vauthors=Kulke MH, Blaszkowsky LS, Ryan DP, Clark JW, Meyerhardt JA, Zhu AX, Enzinger PC, Kwak EL, Muzikansky A, Lawrence C, Fuchs CS |title=Capecitabine plus erlotinib in gemcitabine-refractory advanced pancreatic cancer |journal=J. Clin. Oncol. |volume=25 |issue=30 |pages=4787–92 |year=2007 |pmid=17947726 |doi=10.1200/JCO.2007.11.8521 |url=}}</ref>
:*One year survival of FOLFIRINOX (leucovorin+5-lfuorouracil [LV5-FU]+oxaliplatin+irinotecan)>Gemcitabine<ref name="pmid23341367">{{cite journal |vauthors=Conroy T, Gavoille C, Samalin E, Ychou M, Ducreux M |title=The role of the FOLFIRINOX regimen for advanced pancreatic cancer |journal=Curr Oncol Rep |volume=15 |issue=2 |pages=182–9 |year=2013 |pmid=23341367 |doi=10.1007/s11912-012-0290-4 |url=}}</ref><ref name="pmid23955427">{{cite journal |vauthors=Boone BA, Steve J, Krasinskas AM, Zureikat AH, Lembersky BC, Gibson MK, Stoller RG, Zeh HJ, Bahary N |title=Outcomes with FOLFIRINOX for borderline resectable and locally unresectable pancreatic cancer |journal=J Surg Oncol |volume=108 |issue=4 |pages=236–41 |year=2013 |pmid=23955427 |pmc=3816713 |doi=10.1002/jso.23392 |url=}}</ref><ref name="pmid15718320">{{cite journal |vauthors=Conroy T, Paillot B, François E, Bugat R, Jacob JH, Stein U, Nasca S, Metges JP, Rixe O, Michel P, Magherini E, Hua A, Deplanque G |title=Irinotecan plus oxaliplatin and leucovorin-modulated fluorouracil in advanced pancreatic cancer--a Groupe Tumeurs Digestives of the Federation Nationale des Centres de Lutte Contre le Cancer study |journal=J. Clin. Oncol. |volume=23 |issue=6 |pages=1228–36 |year=2005 |pmid=15718320 |doi=10.1200/JCO.2005.06.050 |url=}}</ref><ref name="pmid22964956" /><ref name="pmid12007953">{{cite journal |vauthors=Shinchi H, Takao S, Noma H, Matsuo Y, Mataki Y, Mori S, Aikou T |title=Length and quality of survival after external-beam radiotherapy with concurrent continuous 5-fluorouracil infusion for locally unresectable pancreatic cancer |journal=Int. J. Radiat. Oncol. Biol. Phys. |volume=53 |issue=1 |pages=146–50 |year=2002 |pmid=12007953 |doi= |url=}}</ref><ref name="pmid426553">{{cite journal |vauthors= |title=A multi-institutional comparative trial of radiation therapy alone and in combination with 5-fluorouracil for locally unresectable pancreatic carcinoma. The Gastrointestinal Tumor Study Group |journal=Ann. Surg. |volume=189 |issue=2 |pages=205–8 |year=1979 |pmid=426553 |pmc=1397020 |doi= |url=}}</ref><ref name="pmid23657686">{{cite journal |vauthors=Faris JE, Blaszkowsky LS, McDermott S, Guimaraes AR, Szymonifka J, Huynh MA, Ferrone CR, Wargo JA, Allen JN, Dias LE, Kwak EL, Lillemoe KD, Thayer SP, Murphy JE, Zhu AX, Sahani DV, Wo JY, Clark JW, Fernandez-del Castillo C, Ryan DP, Hong TS |title=FOLFIRINOX in locally advanced pancreatic cancer: the Massachusetts General Hospital Cancer Center experience |journal=Oncologist |volume=18 |issue=5 |pages=543–8 |year=2013 |pmid=23657686 |pmc=3662845 |doi=10.1634/theoncologist.2012-0435 |url=}}</ref>
:*One year survival of Gemcitabine+ Erlotinib> Gemcitabine<ref name="pmid28541474">{{cite journal |vauthors=Furuse J, Gemma A, Ichikawa W, Okusaka T, Seki A, Ishii T |title=Postmarketing surveillance study of erlotinib plus gemcitabine for pancreatic cancer in Japan: POLARIS final analysis |journal=Jpn. J. Clin. Oncol. |volume=47 |issue=9 |pages=832–839 |year=2017 |pmid=28541474 |doi=10.1093/jjco/hyx075 |url=}}</ref><ref name="pmid28702772">{{cite journal |vauthors=Fountzilas C, Chhatrala R, Khushalani N, Tan W, LeVea C, Hutson A, Tucker C, Ma WW, Warren G, Boland P, Iyer R |title=A phase II trial of erlotinib monotherapy in advanced pancreatic cancer as a first- or second-line agent |journal=Cancer Chemother. Pharmacol. |volume= |issue= |pages= |year=2017 |pmid=28702772 |doi=10.1007/s00280-017-3375-9 |url=}}</ref><ref name="pmid27139057" /><ref name="pmid27139057" />
:*One year survival of Gemcitabine+ Capecitabine ≥ Gemcitabine  <ref name="pmid18669454">{{cite journal |vauthors=Bernhard J, Dietrich D, Scheithauer W, Gerber D, Bodoky G, Ruhstaller T, Glimelius B, Bajetta E, Schüller J, Saletti P, Bauer J, Figer A, Pestalozzi BC, Köhne CH, Mingrone W, Stemmer SM, Tàmas K, Kornek GV, Koeberle D, Herrmann R |title=Clinical benefit and quality of life in patients with advanced pancreatic cancer receiving gemcitabine plus capecitabine versus gemcitabine alone: a randomized multicenter phase III clinical trial--SAKK 44/00-CECOG/PAN.1.3.001 |journal=J. Clin. Oncol. |volume=26 |issue=22 |pages=3695–701 |year=2008 |pmid=18669454 |doi=10.1200/JCO.2007.15.6240 |url=}}</ref><ref name="pmid19858379">{{cite journal |vauthors=Cunningham D, Chau I, Stocken DD, Valle JW, Smith D, Steward W, Harper PG, Dunn J, Tudur-Smith C, West J, Falk S, Crellin A, Adab F, Thompson J, Leonard P, Ostrowski J, Eatock M, Scheithauer W, Herrmann R, Neoptolemos JP |title=Phase III randomized comparison of gemcitabine versus gemcitabine plus capecitabine in patients with advanced pancreatic cancer |journal=J. Clin. Oncol. |volume=27 |issue=33 |pages=5513–8 |year=2009 |pmid=19858379 |doi=10.1200/JCO.2009.24.2446 |url=}}</ref><ref name="pmid20817204">{{cite journal |vauthors=Sahora K, Kuehrer I, Eisenhut A, Akan B, Koellblinger C, Goetzinger P, Teleky B, Jakesz R, Peck-Radosavljevic M, Ba'ssalamah A, Zielinski C, Gnant M |title=NeoGemOx: Gemcitabine and oxaliplatin as neoadjuvant treatment for locally advanced, nonmetastasized pancreatic cancer |journal=Surgery |volume=149 |issue=3 |pages=311–20 |year=2011 |pmid=20817204 |doi=10.1016/j.surg.2010.07.048 |url=}}</ref><ref name="pmid23474363" /><ref name="pmid21213060">{{cite journal |vauthors=Stokes JB, Nolan NJ, Stelow EB, Walters DM, Weiss GR, de Lange EE, Rich TA, Adams RB, Bauer TW |title=Preoperative capecitabine and concurrent radiation for borderline resectable pancreatic cancer |journal=Ann. Surg. Oncol. |volume=18 |issue=3 |pages=619–27 |year=2011 |pmid=21213060 |doi=10.1245/s10434-010-1456-7 |url=}}</ref>
:*One year survival of Gemcitabine+ nanoparticle albumin-bound (nab)-paclitaxel > Gemcitabine<ref name="pmid28820270">{{cite journal |vauthors=Passero FC, Saif MW |title=Second line treatment options for pancreatic cancer |journal=Expert Opin Pharmacother |volume=18 |issue=15 |pages=1607–1617 |year=2017 |pmid=28820270 |doi=10.1080/14656566.2017.1369955 |url=}}</ref><ref name="pmid24939470">{{cite journal |vauthors=Saif MW |title=Advanced stage pancreatic cancer: novel therapeutic options |journal=Expert Rev Clin Pharmacol |volume=7 |issue=4 |pages=487–98 |year=2014 |pmid=24939470 |doi=10.1586/17512433.2014.910451 |url=}}</ref>


==== List of Drugs Approved for Pancreatic Cancer ====
Preferred regimen (1): [[Gemcitabine]] 1000 mg/m <sup>2</sup> IV q30min weekly for 3 weeks
::*Abraxane (Paclitaxel Albumin-stabilized Nanoparticle Formulation)
::*Adrucil (Fluorouracil)
::*Afinitor (Everolimus)
::*Efudex (Fluorouracil)
::*Erlotinib Hydrochloride
::*Everolimus
::*Fluoroplex (Fluorouracil)
::*Fluorouracil
::*Gemcitabine Hydrochloride
::*Gemzar (Gemcitabine Hydrochloride)
::*Mitomycin C
::*Mitozytrex (Mitomycin C)
::*Mutamycin (Mitomycin C)
::*Paclitaxel Albumin-stabilized Nanoparticle Formulation
::*Sunitinib Malate
::*Sutent (Sunitinib Malate)
::*Tarceva (Erlotinib Hydrochloride)


==== List of Drug Combinations Used in Pancreatic Cancer ====
Preferred regimen (2): [[Fluorouracil|5-fluorouracil (FU)]] 250 mg/m <sup>2</sup>/day continuous IV infusion via pump
::*FOLFIRINOX
 
::*GEMCITABINE-CISPLATIN
Preferred regimen (3): [[Radiation therapy|Radiotherapy]] 1.8 Gy/day upto a total of 50.4 Gy; '''then ''' 3-5 wk after chemoradiation: [[Gemcitabine]] 1000 mg/m <sup>2</sup> IV  q30 min weekly; every 4 weeks for three cycles
::*GEMCITABINE-OXALIPLATIN
====''Stage III:''====
::*OFF(Oxaliplatin,Fluorouracil and Folinic Acid)
''Neoadjuvant therapy:''
 
Preferred regimen (1): [[Gemcitabine]] 1000 mg/m <sup>2</sup> IV  q30 min weekly for 3 weeks, every 4 weeks
 
Preferred regimen (2): [[Fluorouracil|5-fluorouracil (FU)]] 500 mg/m <sup>2</sup>/day IV [[Bolus (digestion)|bolus]] on days 1-3 and 29-31 with [[Radiation therapy|radiotherapy]], 40 Gy
 
'''''Stage IV:'''''
*Preferred regimen (1): Protein bound [[Paclitaxel]] 125 mg/m <sup>2</sup> '''AND''' [[Gemcitabine]] 1000 mg/m <sup>2</sup> IV over 30-40 min on days 1, 8, and 15 q4weeks
*Preferred regimen (2): [[Gemcitabine]] 1000 mg/m <sup>2</sup> IV over 30 min q1week for 7 wk, followed by 1 week off, then weekly for 3 wk
*Preferred regimen (3): [[Gemcitabine]] 1000 mg/m <sup>2</sup> IV over 30 min on days 1 and 15 '''AND ''' [[Cisplatin]] 50 mg/m <sup>2</sup> IV over 1 h on days 1 and 15, q4 weeks
*Preferred regimen (3): [[Gemcitabine]] 1000 mg/m <sup>2</sup> IV weekly for 7 wk '''AND ''' [[Erlotinib]] 100 mg PO daily on days 1-56 '''then [[Gemcitabine|G]]'''[[Gemcitabine|emcitabine]] 1000 mg/m <sup>2</sup> IV on days 1, 8, and 15 '''plus ''' [[Erlotinib]] 100 mg PO q24h on days 1-28 in four cycles 
*Preferred regimen (4): [[Gemcitabine]] 1000 mg/m <sup>2</sup> IV weekly for 3 weeks q4weeks '''AND ''' [[Capecitabine]] 1660 mg/m <sup>2</sup>/day weekly for 3 wk; q4weeks
*Preferred regimen (5): [[Oxaliplatin]] 85 mg/m <sup>2</sup> IV '''AND ''' [[Irinotecan]] 180 mg/m <sup>2</sup> IV on day 1 '''AND ''' [[Leucovorin]] 400 mg/m <sup>2</sup> IV on day 1, followed by [[Fluorouracil|5-fluorouracil (FU)]]  400 mg/m <sup>2</sup> IV bolus on day 1 and then 2400 mg/m <sup>2</sup> IV [[Intravenous therapy|infusion]] over 46 h on days 1 and 15
''Alternative treatment recommendations for Stage IV:''
*Alternative regimen (1): [[Capecitabine]] 1250 mg/m <sup>2</sup> PO q12h for 2 weeks, every 3 weeks 
*Alternative regimen (2): [[Capecitabine]] 1000 mg/m <sup>2</sup> PO q12h for 2 weeks; every 3 weeks '''AND''' [[Erlotinib]] 150 mg PO daily
*Alternative regimen (3): [[Irinotecan]] [[Liposome|liposomal]] 70 mg/m <sup>2</sup> IV infused over 1.5h '''AND'''  [[Leucovorin]] 400 mg/m <sup>2</sup> IV infused over 30min ,'''followed by ''' [[Fluorouracil|5-fluorouracil (FU)]]  2400 mg/m <sup>2</sup> IV infused over 46 h q3 weeks 
*Alternative regimen (4):  [[Fluorouracil|5-fluorouracil (FU)]]  2000 mg/m <sup>2</sup> IV continuous on days 1, 8, 15, and 22 '''AND '''[[Leucovorin]] 200 mg/m <sup>2</sup> IV over .5h on days 1, 8, 15, and 22 '''AND''' [[Oxaliplatin]] 85 mg/m <sup>2</sup> IV on days 8 and 22; q42d
 
Comparison of ''one year survival'' of various regimens is depicted in the table below:
{| class="wikitable"
! style="background:#4479BA; color: #FFFFFF;" |ONE YEAR SURVIVAL OF DIFFERENT REGIMENS
|-
|One year survival of [[FOLFIRINOX regimen|FOLFIRINOX]] ([[leucovorin]] '''AND''' 5-[[fluorouracil]] [LV5-FU] '''AND''' [[oxaliplatin]] '''AND''' [[Irinotecan]]) is better than [[Gemcitabine]]<ref name="pmid22964956" /><ref name="pmid23341367">{{cite journal |vauthors=Conroy T, Gavoille C, Samalin E, Ychou M, Ducreux M |title=The role of the FOLFIRINOX regimen for advanced pancreatic cancer |journal=Curr Oncol Rep |volume=15 |issue=2 |pages=182–9 |year=2013 |pmid=23341367 |doi=10.1007/s11912-012-0290-4 |url=}}</ref><ref name="pmid23955427">{{cite journal |vauthors=Boone BA, Steve J, Krasinskas AM, Zureikat AH, Lembersky BC, Gibson MK, Stoller RG, Zeh HJ, Bahary N |title=Outcomes with FOLFIRINOX for borderline resectable and locally unresectable pancreatic cancer |journal=J Surg Oncol |volume=108 |issue=4 |pages=236–41 |year=2013 |pmid=23955427 |pmc=3816713 |doi=10.1002/jso.23392 |url=}}</ref><ref name="pmid15718320">{{cite journal |vauthors=Conroy T, Paillot B, François E, Bugat R, Jacob JH, Stein U, Nasca S, Metges JP, Rixe O, Michel P, Magherini E, Hua A, Deplanque G |title=Irinotecan plus oxaliplatin and leucovorin-modulated fluorouracil in advanced pancreatic cancer--a Groupe Tumeurs Digestives of the Federation Nationale des Centres de Lutte Contre le Cancer study |journal=J. Clin. Oncol. |volume=23 |issue=6 |pages=1228–36 |year=2005 |pmid=15718320 |doi=10.1200/JCO.2005.06.050 |url=}}</ref><ref name="pmid12007953">{{cite journal |vauthors=Shinchi H, Takao S, Noma H, Matsuo Y, Mataki Y, Mori S, Aikou T |title=Length and quality of survival after external-beam radiotherapy with concurrent continuous 5-fluorouracil infusion for locally unresectable pancreatic cancer |journal=Int. J. Radiat. Oncol. Biol. Phys. |volume=53 |issue=1 |pages=146–50 |year=2002 |pmid=12007953 |doi= |url=}}</ref><ref name="pmid426553">{{cite journal |vauthors= |title=A multi-institutional comparative trial of radiation therapy alone and in combination with 5-fluorouracil for locally unresectable pancreatic carcinoma. The Gastrointestinal Tumor Study Group |journal=Ann. Surg. |volume=189 |issue=2 |pages=205–8 |year=1979 |pmid=426553 |pmc=1397020 |doi= |url=}}</ref><ref name="pmid23657686">{{cite journal |vauthors=Faris JE, Blaszkowsky LS, McDermott S, Guimaraes AR, Szymonifka J, Huynh MA, Ferrone CR, Wargo JA, Allen JN, Dias LE, Kwak EL, Lillemoe KD, Thayer SP, Murphy JE, Zhu AX, Sahani DV, Wo JY, Clark JW, Fernandez-del Castillo C, Ryan DP, Hong TS |title=FOLFIRINOX in locally advanced pancreatic cancer: the Massachusetts General Hospital Cancer Center experience |journal=Oncologist |volume=18 |issue=5 |pages=543–8 |year=2013 |pmid=23657686 |pmc=3662845 |doi=10.1634/theoncologist.2012-0435 |url=}}</ref>
|-
|One year survival of [[Gemcitabine]] '''AND''' [[Erlotinib]] is better than [[Gemcitabine]]<ref name="pmid27139057" /><ref name="pmid28541474">{{cite journal |vauthors=Furuse J, Gemma A, Ichikawa W, Okusaka T, Seki A, Ishii T |title=Postmarketing surveillance study of erlotinib plus gemcitabine for pancreatic cancer in Japan: POLARIS final analysis |journal=Jpn. J. Clin. Oncol. |volume=47 |issue=9 |pages=832–839 |year=2017 |pmid=28541474 |doi=10.1093/jjco/hyx075 |url=}}</ref><ref name="pmid28702772">{{cite journal |vauthors=Fountzilas C, Chhatrala R, Khushalani N, Tan W, LeVea C, Hutson A, Tucker C, Ma WW, Warren G, Boland P, Iyer R |title=A phase II trial of erlotinib monotherapy in advanced pancreatic cancer as a first- or second-line agent |journal=Cancer Chemother. Pharmacol. |volume= |issue= |pages= |year=2017 |pmid=28702772 |doi=10.1007/s00280-017-3375-9 |url=}}</ref>
|-
|One year survival of [[Gemcitabine]] '''AND''' [[Capecitabine]] is better than or equal to [[Gemcitabine]] <ref name="pmid23474363" /><ref name="pmid18669454">{{cite journal |vauthors=Bernhard J, Dietrich D, Scheithauer W, Gerber D, Bodoky G, Ruhstaller T, Glimelius B, Bajetta E, Schüller J, Saletti P, Bauer J, Figer A, Pestalozzi BC, Köhne CH, Mingrone W, Stemmer SM, Tàmas K, Kornek GV, Koeberle D, Herrmann R |title=Clinical benefit and quality of life in patients with advanced pancreatic cancer receiving gemcitabine plus capecitabine versus gemcitabine alone: a randomized multicenter phase III clinical trial--SAKK 44/00-CECOG/PAN.1.3.001 |journal=J. Clin. Oncol. |volume=26 |issue=22 |pages=3695–701 |year=2008 |pmid=18669454 |doi=10.1200/JCO.2007.15.6240 |url=}}</ref><ref name="pmid19858379">{{cite journal |vauthors=Cunningham D, Chau I, Stocken DD, Valle JW, Smith D, Steward W, Harper PG, Dunn J, Tudur-Smith C, West J, Falk S, Crellin A, Adab F, Thompson J, Leonard P, Ostrowski J, Eatock M, Scheithauer W, Herrmann R, Neoptolemos JP |title=Phase III randomized comparison of gemcitabine versus gemcitabine plus capecitabine in patients with advanced pancreatic cancer |journal=J. Clin. Oncol. |volume=27 |issue=33 |pages=5513–8 |year=2009 |pmid=19858379 |doi=10.1200/JCO.2009.24.2446 |url=}}</ref><ref name="pmid20817204">{{cite journal |vauthors=Sahora K, Kuehrer I, Eisenhut A, Akan B, Koellblinger C, Goetzinger P, Teleky B, Jakesz R, Peck-Radosavljevic M, Ba'ssalamah A, Zielinski C, Gnant M |title=NeoGemOx: Gemcitabine and oxaliplatin as neoadjuvant treatment for locally advanced, nonmetastasized pancreatic cancer |journal=Surgery |volume=149 |issue=3 |pages=311–20 |year=2011 |pmid=20817204 |doi=10.1016/j.surg.2010.07.048 |url=}}</ref><ref name="pmid21213060">{{cite journal |vauthors=Stokes JB, Nolan NJ, Stelow EB, Walters DM, Weiss GR, de Lange EE, Rich TA, Adams RB, Bauer TW |title=Preoperative capecitabine and concurrent radiation for borderline resectable pancreatic cancer |journal=Ann. Surg. Oncol. |volume=18 |issue=3 |pages=619–27 |year=2011 |pmid=21213060 |doi=10.1245/s10434-010-1456-7 |url=}}</ref>
|-
|One year survival of [[Gemcitabine]] '''AND''' nanoparticle albumin-bound (nab)-[[Paclitaxel]] is better than [[Gemcitabine]]<ref name="pmid28820270">{{cite journal |vauthors=Passero FC, Saif MW |title=Second line treatment options for pancreatic cancer |journal=Expert Opin Pharmacother |volume=18 |issue=15 |pages=1607–1617 |year=2017 |pmid=28820270 |doi=10.1080/14656566.2017.1369955 |url=}}</ref><ref name="pmid24939470">{{cite journal |vauthors=Saif MW |title=Advanced stage pancreatic cancer: novel therapeutic options |journal=Expert Rev Clin Pharmacol |volume=7 |issue=4 |pages=487–98 |year=2014 |pmid=24939470 |doi=10.1586/17512433.2014.910451 |url=}}</ref>
|}


===Radiation Therapy===
===Radiation Therapy===
* The role of [[radiation therapy|radiotherapy]] as an auxiliary (adjuvant) treatment after potentially curative surgery is controversial. <ref name="pmid9850029">{{cite journal |vauthors=Pisters PW, Abbruzzese JL, Janjan NA, Cleary KR, Charnsangavej C, Goswitz MS, Rich TA, Raijman I, Wolff RA, Lenzi R, Lee JE, Evans DB |title=Rapid-fractionation preoperative chemoradiation, pancreaticoduodenectomy, and intraoperative radiation therapy for resectable pancreatic adenocarcinoma |journal=J. Clin. Oncol. |volume=16 |issue=12 |pages=3843–50 |year=1998 |pmid=9850029 |doi=10.1200/JCO.1998.16.12.3843 |url=}}</ref><ref name="pmid20083754" />
* The role of [[radiation therapy|radiotherapy]] as an auxiliary ([[adjuvant]]) treatment after potentially curative [[surgery]] is controversial.<ref name="pmid9850029">{{cite journal |vauthors=Pisters PW, Abbruzzese JL, Janjan NA, Cleary KR, Charnsangavej C, Goswitz MS, Rich TA, Raijman I, Wolff RA, Lenzi R, Lee JE, Evans DB |title=Rapid-fractionation preoperative chemoradiation, pancreaticoduodenectomy, and intraoperative radiation therapy for resectable pancreatic adenocarcinoma |journal=J. Clin. Oncol. |volume=16 |issue=12 |pages=3843–50 |year=1998 |pmid=9850029 |doi=10.1200/JCO.1998.16.12.3843 |url=}}</ref><ref name="pmid20083754" /><ref name="pmid150288242">{{cite journal |author=Neoptolemos JP, Stocken DD, Friess H, ''et al'' |title=A randomized trial of chemoradiotherapy and chemotherapy after resection of pancreatic cancer |journal=N. Engl. J. Med. |volume=350 |issue=12 |pages=1200–10 |year=2004 |pmid=15028824 |doi=10.1056/NEJMoa032295}}</ref>
* Radiotherapy may form part of neoadjuvant therapy to attempt to shrink a tumor to a resectable state, but its use on unresectable tumors remains controversial.<ref name="pmid25599322" /><ref name="pmid21969502">{{cite journal |vauthors=Loehrer PJ, Feng Y, Cardenes H, Wagner L, Brell JM, Cella D, Flynn P, Ramanathan RK, Crane CH, Alberts SR, Benson AB |title=Gemcitabine alone versus gemcitabine plus radiotherapy in patients with locally advanced pancreatic cancer: an Eastern Cooperative Oncology Group trial |journal=J. Clin. Oncol. |volume=29 |issue=31 |pages=4105–12 |year=2011 |pmid=21969502 |pmc=3525836 |doi=10.1200/JCO.2011.34.8904 |url=}}</ref>
* [[Radiation therapy|Radiotherapy]] may form part of [[neoadjuvant therapy]] to attempt to shrink a [[tumor]] to a resectable state, but its use on unresectable [[Tumor|tumors]] remains controversial.<ref name="pmid25599322" /><ref name="pmid21969502">{{cite journal |vauthors=Loehrer PJ, Feng Y, Cardenes H, Wagner L, Brell JM, Cella D, Flynn P, Ramanathan RK, Crane CH, Alberts SR, Benson AB |title=Gemcitabine alone versus gemcitabine plus radiotherapy in patients with locally advanced pancreatic cancer: an Eastern Cooperative Oncology Group trial |journal=J. Clin. Oncol. |volume=29 |issue=31 |pages=4105–12 |year=2011 |pmid=21969502 |pmc=3525836 |doi=10.1200/JCO.2011.34.8904 |url=}}</ref>


=== Palliative Therapy ===
=== Palliative Therapy ===
* Pain:  
Palliative therapy in patients with pancreatic cancer mainly involves the management of symptoms arising as a result of complications of therapy:<ref name="pmid28890822">{{cite journal |vauthors=Kulaylat AS, Mirkin KA, Hollenbeak CS, Wong J |title=Utilization and trends in palliative therapy for stage IV pancreatic adenocarcinoma patients: a U.S. population-based study |journal=J Gastrointest Oncol |volume=8 |issue=4 |pages=710–720 |year=2017 |pmid=28890822 |pmc=5582050 |doi=10.21037/jgo.2017.06.01 |url=}}</ref><ref name="pmid28850428">{{cite journal |vauthors=Mastenbroek TC, Kramp-Hendriks BJ, Kallewaard JW, Vonk JM |title=Multimodal intrathecal analgesia in refractory cancer pain |journal=Scand J Pain |volume=14 |issue= |pages=39–43 |year=2017 |pmid=28850428 |doi=10.1016/j.sjpain.2016.10.002 |url=}}</ref><ref name="pmid28772092">{{cite journal |vauthors=Schenker Y, Bahary N, Claxton R, Childers J, Chu E, Kavalieratos D, King L, Lembersky B, Tiver G, Arnold RM |title=A Pilot Trial of Early Specialty Palliative Care for Patients with Advanced Pancreatic Cancer: Challenges Encountered and Lessons Learned |journal=J Palliat Med |volume= |issue= |pages= |year=2017 |pmid=28772092 |doi=10.1089/jpm.2017.0113 |url=}}</ref><ref name="pmid28734721">{{cite journal |vauthors=Ouyang H, Ma W, Liu F, Yue Z, Fang M, Quan M, Pan Z |title=Factors influencing survival of patients with pancreatic adenocarcinoma and synchronous liver metastases receiving palliative care |journal=Pancreatology |volume=17 |issue=5 |pages=773–781 |year=2017 |pmid=28734721 |doi=10.1016/j.pan.2017.07.002 |url=}}</ref><ref name="pmid28705009">{{cite journal |vauthors=Agarwal R, Epstein AS |title=Palliative care and advance care planning for pancreas and other cancers |journal=Chin Clin Oncol |volume=6 |issue=3 |pages=32 |year=2017 |pmid=28705009 |doi=10.21037/cco.2017.06.16 |url=}}</ref><ref name="pmid28612201">{{cite journal |vauthors=Laquente B, Calsina-Berna A, Carmona-Bayonas A, Jiménez-Fonseca P, Peiró I, Carrato A |title=Supportive care in pancreatic ductal adenocarcinoma |journal=Clin Transl Oncol |volume= |issue= |pages= |year=2017 |pmid=28612201 |doi=10.1007/s12094-017-1682-6 |url=}}</ref>
** There are various techniques for pain management as palliative therapy in patients with advanced stage of pancreatic cancer:
* [[Pain]]:  
*** Narcotic analgesics  
** There are various techniques for [[pain]] management as [[Palliative care|palliative therapy]] in patients with advanced stage of [[pancreatic cancer]]:
*** Narcotic analgesics+ tricyclic antidepressants/ antiemetics  
*** [[Narcotic]] [[Analgesic|analgesics]]
*** Radiation therapy
*** [[Narcotic]] [[Analgesic|analgesics]] '''AND''' [[Tricyclic antidepressant|tricyclic antidepressants]] or [[Antiemetic|antiemetics]]
*** [[Radiation therapy]]


=== Adjuvant and Neoadjuvant therapy ===
=== Adjuvant and Neoadjuvant therapy ===
* The use of gemcitabine as adjuvant therapy is considered a standard form of therapy following surgical resection in pancreatic cancer patients.<ref name="pmid4015380">{{cite journal |vauthors=Kalser MH, Ellenberg SS |title=Pancreatic cancer. Adjuvant combined radiation and chemotherapy following curative resection |journal=Arch Surg |volume=120 |issue=8 |pages=899–903 |year=1985 |pmid=4015380 |doi= |url=}}</ref><ref name="pmid15028824">{{cite journal |vauthors=Neoptolemos JP, Stocken DD, Friess H, Bassi C, Dunn JA, Hickey H, Beger H, Fernandez-Cruz L, Dervenis C, Lacaine F, Falconi M, Pederzoli P, Pap A, Spooner D, Kerr DJ, Büchler MW |title=A randomized trial of chemoradiotherapy and chemotherapy after resection of pancreatic cancer |journal=N. Engl. J. Med. |volume=350 |issue=12 |pages=1200–10 |year=2004 |pmid=15028824 |doi=10.1056/NEJMoa032295 |url=}}</ref><ref name="pmid20083754">{{cite journal |vauthors=Yang R, Cheung MC, Byrne MM, Jin X, Montero AJ, Jones C, Koniaris LG |title=Survival effects of adjuvant chemoradiotherapy after resection for pancreatic carcinoma |journal=Arch Surg |volume=145 |issue=1 |pages=49–56 |year=2010 |pmid=20083754 |doi=10.1001/archsurg.2009.244 |url=}}</ref><ref name="pmid17227978">{{cite journal |vauthors=Oettle H, Post S, Neuhaus P, Gellert K, Langrehr J, Ridwelski K, Schramm H, Fahlke J, Zuelke C, Burkart C, Gutberlet K, Kettner E, Schmalenberg H, Weigang-Koehler K, Bechstein WO, Niedergethmann M, Schmidt-Wolf I, Roll L, Doerken B, Riess H |title=Adjuvant chemotherapy with gemcitabine vs observation in patients undergoing curative-intent resection of pancreatic cancer: a randomized controlled trial |journal=JAMA |volume=297 |issue=3 |pages=267–77 |year=2007 |pmid=17227978 |doi=10.1001/jama.297.3.267 |url=}}</ref><ref name="pmid24035532">{{cite journal |vauthors=Liao WC, Chien KL, Lin YL, Wu MS, Lin JT, Wang HP, Tu YK |title=Adjuvant treatments for resected pancreatic adenocarcinoma: a systematic review and network meta-analysis |journal=Lancet Oncol. |volume=14 |issue=11 |pages=1095–103 |year=2013 |pmid=24035532 |doi=10.1016/S1470-2045(13)70388-7 |url=}}</ref><ref name="pmid24419109">{{cite journal |vauthors=Valle JW, Palmer D, Jackson R, Cox T, Neoptolemos JP, Ghaneh P, Rawcliffe CL, Bassi C, Stocken DD, Cunningham D, O'Reilly D, Goldstein D, Robinson BA, Karapetis C, Scarfe A, Lacaine F, Sand J, Izbicki JR, Mayerle J, Dervenis C, Oláh A, Butturini G, Lind PA, Middleton MR, Anthoney A, Sumpter K, Carter R, Büchler MW |title=Optimal duration and timing of adjuvant chemotherapy after definitive surgery for ductal adenocarcinoma of the pancreas: ongoing lessons from the ESPAC-3 study |journal=J. Clin. Oncol. |volume=32 |issue=6 |pages=504–12 |year=2014 |pmid=24419109 |doi=10.1200/JCO.2013.50.7657 |url=}}</ref><ref name="pmid27328270">{{cite journal |vauthors=Mirkin KA, Greenleaf EK, Hollenbeak CS, Wong J |title=Time to the initiation of adjuvant chemotherapy does not impact survival in patients with resected pancreatic cancer |journal=Cancer |volume=122 |issue=19 |pages=2979–87 |year=2016 |pmid=27328270 |doi=10.1002/cncr.30163 |url=}}</ref><ref name="pmid28129987">{{cite journal |vauthors=Neoptolemos JP, Palmer DH, Ghaneh P, Psarelli EE, Valle JW, Halloran CM, Faluyi O, O'Reilly DA, Cunningham D, Wadsley J, Darby S, Meyer T, Gillmore R, Anthoney A, Lind P, Glimelius B, Falk S, Izbicki JR, Middleton GW, Cummins S, Ross PJ, Wasan H, McDonald A, Crosby T, Ma YT, Patel K, Sherriff D, Soomal R, Borg D, Sothi S, Hammel P, Hackert T, Jackson R, Büchler MW |title=Comparison of adjuvant gemcitabine and capecitabine with gemcitabine monotherapy in patients with resected pancreatic cancer (ESPAC-4): a multicentre, open-label, randomised, phase 3 trial |journal=Lancet |volume=389 |issue=10073 |pages=1011–1024 |year=2017 |pmid=28129987 |doi=10.1016/S0140-6736(16)32409-6 |url=}}</ref><ref name="pmid8471327">{{cite journal |vauthors=Bakkevold KE, Arnesjø B, Dahl O, Kambestad B |title=Adjuvant combination chemotherapy (AMF) following radical resection of carcinoma of the pancreas and papilla of Vater--results of a controlled, prospective, randomised multicentre study |journal=Eur. J. Cancer |volume=29A |issue=5 |pages=698–703 |year=1993 |pmid=8471327 |doi= |url=}}</ref><ref name="pmid20817204">{{cite journal |vauthors=Sahora K, Kuehrer I, Eisenhut A, Akan B, Koellblinger C, Goetzinger P, Teleky B, Jakesz R, Peck-Radosavljevic M, Ba'ssalamah A, Zielinski C, Gnant M |title=NeoGemOx: Gemcitabine and oxaliplatin as neoadjuvant treatment for locally advanced, nonmetastasized pancreatic cancer |journal=Surgery |volume=149 |issue=3 |pages=311–20 |year=2011 |pmid=20817204 |doi=10.1016/j.surg.2010.07.048 |url=}}</ref>
* The use of [[gemcitabine]] as [[adjuvant therapy]] is considered a standard form of therapy following surgical [[resection]] in [[pancreatic cancer]] patients.<ref name="pmid20817204">{{cite journal |vauthors=Sahora K, Kuehrer I, Eisenhut A, Akan B, Koellblinger C, Goetzinger P, Teleky B, Jakesz R, Peck-Radosavljevic M, Ba'ssalamah A, Zielinski C, Gnant M |title=NeoGemOx: Gemcitabine and oxaliplatin as neoadjuvant treatment for locally advanced, nonmetastasized pancreatic cancer |journal=Surgery |volume=149 |issue=3 |pages=311–20 |year=2011 |pmid=20817204 |doi=10.1016/j.surg.2010.07.048 |url=}}</ref><ref name="pmid20083754">{{cite journal |vauthors=Yang R, Cheung MC, Byrne MM, Jin X, Montero AJ, Jones C, Koniaris LG |title=Survival effects of adjuvant chemoradiotherapy after resection for pancreatic carcinoma |journal=Arch Surg |volume=145 |issue=1 |pages=49–56 |year=2010 |pmid=20083754 |doi=10.1001/archsurg.2009.244 |url=}}</ref><ref name="pmid4015380">{{cite journal |vauthors=Kalser MH, Ellenberg SS |title=Pancreatic cancer. Adjuvant combined radiation and chemotherapy following curative resection |journal=Arch Surg |volume=120 |issue=8 |pages=899–903 |year=1985 |pmid=4015380 |doi= |url=}}</ref><ref name="pmid15028824">{{cite journal |vauthors=Neoptolemos JP, Stocken DD, Friess H, Bassi C, Dunn JA, Hickey H, Beger H, Fernandez-Cruz L, Dervenis C, Lacaine F, Falconi M, Pederzoli P, Pap A, Spooner D, Kerr DJ, Büchler MW |title=A randomized trial of chemoradiotherapy and chemotherapy after resection of pancreatic cancer |journal=N. Engl. J. Med. |volume=350 |issue=12 |pages=1200–10 |year=2004 |pmid=15028824 |doi=10.1056/NEJMoa032295 |url=}}</ref><ref name="pmid17227978">{{cite journal |vauthors=Oettle H, Post S, Neuhaus P, Gellert K, Langrehr J, Ridwelski K, Schramm H, Fahlke J, Zuelke C, Burkart C, Gutberlet K, Kettner E, Schmalenberg H, Weigang-Koehler K, Bechstein WO, Niedergethmann M, Schmidt-Wolf I, Roll L, Doerken B, Riess H |title=Adjuvant chemotherapy with gemcitabine vs observation in patients undergoing curative-intent resection of pancreatic cancer: a randomized controlled trial |journal=JAMA |volume=297 |issue=3 |pages=267–77 |year=2007 |pmid=17227978 |doi=10.1001/jama.297.3.267 |url=}}</ref><ref name="pmid24035532">{{cite journal |vauthors=Liao WC, Chien KL, Lin YL, Wu MS, Lin JT, Wang HP, Tu YK |title=Adjuvant treatments for resected pancreatic adenocarcinoma: a systematic review and network meta-analysis |journal=Lancet Oncol. |volume=14 |issue=11 |pages=1095–103 |year=2013 |pmid=24035532 |doi=10.1016/S1470-2045(13)70388-7 |url=}}</ref><ref name="pmid24419109">{{cite journal |vauthors=Valle JW, Palmer D, Jackson R, Cox T, Neoptolemos JP, Ghaneh P, Rawcliffe CL, Bassi C, Stocken DD, Cunningham D, O'Reilly D, Goldstein D, Robinson BA, Karapetis C, Scarfe A, Lacaine F, Sand J, Izbicki JR, Mayerle J, Dervenis C, Oláh A, Butturini G, Lind PA, Middleton MR, Anthoney A, Sumpter K, Carter R, Büchler MW |title=Optimal duration and timing of adjuvant chemotherapy after definitive surgery for ductal adenocarcinoma of the pancreas: ongoing lessons from the ESPAC-3 study |journal=J. Clin. Oncol. |volume=32 |issue=6 |pages=504–12 |year=2014 |pmid=24419109 |doi=10.1200/JCO.2013.50.7657 |url=}}</ref><ref name="pmid27328270">{{cite journal |vauthors=Mirkin KA, Greenleaf EK, Hollenbeak CS, Wong J |title=Time to the initiation of adjuvant chemotherapy does not impact survival in patients with resected pancreatic cancer |journal=Cancer |volume=122 |issue=19 |pages=2979–87 |year=2016 |pmid=27328270 |doi=10.1002/cncr.30163 |url=}}</ref><ref name="pmid28129987">{{cite journal |vauthors=Neoptolemos JP, Palmer DH, Ghaneh P, Psarelli EE, Valle JW, Halloran CM, Faluyi O, O'Reilly DA, Cunningham D, Wadsley J, Darby S, Meyer T, Gillmore R, Anthoney A, Lind P, Glimelius B, Falk S, Izbicki JR, Middleton GW, Cummins S, Ross PJ, Wasan H, McDonald A, Crosby T, Ma YT, Patel K, Sherriff D, Soomal R, Borg D, Sothi S, Hammel P, Hackert T, Jackson R, Büchler MW |title=Comparison of adjuvant gemcitabine and capecitabine with gemcitabine monotherapy in patients with resected pancreatic cancer (ESPAC-4): a multicentre, open-label, randomised, phase 3 trial |journal=Lancet |volume=389 |issue=10073 |pages=1011–1024 |year=2017 |pmid=28129987 |doi=10.1016/S0140-6736(16)32409-6 |url=}}</ref><ref name="pmid8471327">{{cite journal |vauthors=Bakkevold KE, Arnesjø B, Dahl O, Kambestad B |title=Adjuvant combination chemotherapy (AMF) following radical resection of carcinoma of the pancreas and papilla of Vater--results of a controlled, prospective, randomised multicentre study |journal=Eur. J. Cancer |volume=29A |issue=5 |pages=698–703 |year=1993 |pmid=8471327 |doi= |url=}}</ref>


* Neoadjuvant therapy may be used as a form of therapy due to the following reasons:<ref name="pmid12011133">{{cite journal |vauthors=Pisters PW, Wolff RA, Janjan NA, Cleary KR, Charnsangavej C, Crane CN, Lenzi R, Vauthey JN, Lee JE, Abbruzzese JL, Evans DB |title=Preoperative paclitaxel and concurrent rapid-fractionation radiation for resectable pancreatic adenocarcinoma: toxicities, histologic response rates, and event-free outcome |journal=J. Clin. Oncol. |volume=20 |issue=10 |pages=2537–44 |year=2002 |pmid=12011133 |doi=10.1200/JCO.2002.11.064 |url=}}</ref><ref name="pmid24306217">{{cite journal |vauthors=Kadera BE, Sunjaya DB, Isacoff WH, Li L, Hines OJ, Tomlinson JS, Dawson DW, Rochefort MM, Donald GW, Clerkin BM, Reber HA, Donahue TR |title=Locally advanced pancreatic cancer: association between prolonged preoperative treatment and lymph-node negativity and overall survival |journal=JAMA Surg |volume=149 |issue=2 |pages=145–53 |year=2014 |pmid=24306217 |doi=10.1001/jamasurg.2013.2690 |url=}}</ref><ref name="pmid23838925">{{cite journal |vauthors=Motoi F, Ishida K, Fujishima F, Ottomo S, Oikawa M, Okada T, Shimamura H, Takemura S, Ono F, Akada M, Nakagawa K, Katayose Y, Egawa S, Unno M |title=Neoadjuvant chemotherapy with gemcitabine and S-1 for resectable and borderline pancreatic ductal adenocarcinoma: results from a prospective multi-institutional phase 2 trial |journal=Ann. Surg. Oncol. |volume=20 |issue=12 |pages=3794–801 |year=2013 |pmid=23838925 |doi=10.1245/s10434-013-3129-9 |url=}}</ref><ref name="pmid19307501">{{cite journal |vauthors=Huguet F, Girard N, Guerche CS, Hennequin C, Mornex F, Azria D |title=Chemoradiotherapy in the management of locally advanced pancreatic carcinoma: a qualitative systematic review |journal=J. Clin. Oncol. |volume=27 |issue=13 |pages=2269–77 |year=2009 |pmid=19307501 |doi=10.1200/JCO.2008.19.7921 |url=}}</ref><ref name="pmid20422030">{{cite journal |vauthors=Gillen S, Schuster T, Meyer Zum Büschenfelde C, Friess H, Kleeff J |title=Preoperative/neoadjuvant therapy in pancreatic cancer: a systematic review and meta-analysis of response and resection percentages |journal=PLoS Med. |volume=7 |issue=4 |pages=e1000267 |year=2010 |pmid=20422030 |pmc=2857873 |doi=10.1371/journal.pmed.1000267 |url=}}</ref><ref name="pmid22012027">{{cite journal |vauthors=Andriulli A, Festa V, Botteri E, Valvano MR, Koch M, Bassi C, Maisonneuve P, Sebastiano PD |title=Neoadjuvant/preoperative gemcitabine for patients with localized pancreatic cancer: a meta-analysis of prospective studies |journal=Ann. Surg. Oncol. |volume=19 |issue=5 |pages=1644–62 |year=2012 |pmid=22012027 |doi=10.1245/s10434-011-2110-8 |url=}}</ref><ref name="pmid18308215">{{cite journal |vauthors=Greer SE, Pipas JM, Sutton JE, Zaki BI, Tsapakos M, Colacchio TA, Gibson JJ, Wiener DC, Ripple GH, Barth RJ |title=Effect of neoadjuvant therapy on local recurrence after resection of pancreatic adenocarcinoma |journal=J. Am. Coll. Surg. |volume=206 |issue=3 |pages=451–7 |year=2008 |pmid=18308215 |doi=10.1016/j.jamcollsurg.2007.10.002 |url=}}</ref><ref name="pmid12399067">{{cite journal |vauthors=Kim HJ, Czischke K, Brennan MF, Conlon KC |title=Does neoadjuvant chemoradiation downstage locally advanced pancreatic cancer? |journal=J. Gastrointest. Surg. |volume=6 |issue=5 |pages=763–9 |year=2002 |pmid=12399067 |doi= |url=}}</ref><ref name="pmid10487547">{{cite journal |vauthors=Bajetta E, Di Bartolomeo M, Stani SC, Artale S, Ricci SB, Bozzetti F, Mazzaferro V, Toffolatti L, Buzzoni R |title=Chemoradiotherapy as preoperative treatment in locally advanced unresectable pancreatic cancer patients: results of a feasibility study |journal=Int. J. Radiat. Oncol. Biol. Phys. |volume=45 |issue=2 |pages=285–9 |year=1999 |pmid=10487547 |doi= |url=}}</ref><ref name="pmid25599322">{{cite journal |vauthors=Ferrone CR, Marchegiani G, Hong TS, Ryan DP, Deshpande V, McDonnell EI, Sabbatino F, Santos DD, Allen JN, Blaszkowsky LS, Clark JW, Faris JE, Goyal L, Kwak EL, Murphy JE, Ting DT, Wo JY, Zhu AX, Warshaw AL, Lillemoe KD, Fernández-del Castillo C |title=Radiological and surgical implications of neoadjuvant treatment with FOLFIRINOX for locally advanced and borderline resectable pancreatic cancer |journal=Ann. Surg. |volume=261 |issue=1 |pages=12–7 |year=2015 |pmid=25599322 |pmc=4349683 |doi=10.1097/SLA.0000000000000867 |url=}}</ref>
* [[Neoadjuvant therapy]] may be used as a form of [[therapy]] due to the following reasons:<ref name="pmid19307501">{{cite journal |vauthors=Huguet F, Girard N, Guerche CS, Hennequin C, Mornex F, Azria D |title=Chemoradiotherapy in the management of locally advanced pancreatic carcinoma: a qualitative systematic review |journal=J. Clin. Oncol. |volume=27 |issue=13 |pages=2269–77 |year=2009 |pmid=19307501 |doi=10.1200/JCO.2008.19.7921 |url=}}</ref><ref name="pmid25599322">{{cite journal |vauthors=Ferrone CR, Marchegiani G, Hong TS, Ryan DP, Deshpande V, McDonnell EI, Sabbatino F, Santos DD, Allen JN, Blaszkowsky LS, Clark JW, Faris JE, Goyal L, Kwak EL, Murphy JE, Ting DT, Wo JY, Zhu AX, Warshaw AL, Lillemoe KD, Fernández-del Castillo C |title=Radiological and surgical implications of neoadjuvant treatment with FOLFIRINOX for locally advanced and borderline resectable pancreatic cancer |journal=Ann. Surg. |volume=261 |issue=1 |pages=12–7 |year=2015 |pmid=25599322 |pmc=4349683 |doi=10.1097/SLA.0000000000000867 |url=}}</ref><ref name="pmid12011133">{{cite journal |vauthors=Pisters PW, Wolff RA, Janjan NA, Cleary KR, Charnsangavej C, Crane CN, Lenzi R, Vauthey JN, Lee JE, Abbruzzese JL, Evans DB |title=Preoperative paclitaxel and concurrent rapid-fractionation radiation for resectable pancreatic adenocarcinoma: toxicities, histologic response rates, and event-free outcome |journal=J. Clin. Oncol. |volume=20 |issue=10 |pages=2537–44 |year=2002 |pmid=12011133 |doi=10.1200/JCO.2002.11.064 |url=}}</ref><ref name="pmid24306217">{{cite journal |vauthors=Kadera BE, Sunjaya DB, Isacoff WH, Li L, Hines OJ, Tomlinson JS, Dawson DW, Rochefort MM, Donald GW, Clerkin BM, Reber HA, Donahue TR |title=Locally advanced pancreatic cancer: association between prolonged preoperative treatment and lymph-node negativity and overall survival |journal=JAMA Surg |volume=149 |issue=2 |pages=145–53 |year=2014 |pmid=24306217 |doi=10.1001/jamasurg.2013.2690 |url=}}</ref><ref name="pmid23838925">{{cite journal |vauthors=Motoi F, Ishida K, Fujishima F, Ottomo S, Oikawa M, Okada T, Shimamura H, Takemura S, Ono F, Akada M, Nakagawa K, Katayose Y, Egawa S, Unno M |title=Neoadjuvant chemotherapy with gemcitabine and S-1 for resectable and borderline pancreatic ductal adenocarcinoma: results from a prospective multi-institutional phase 2 trial |journal=Ann. Surg. Oncol. |volume=20 |issue=12 |pages=3794–801 |year=2013 |pmid=23838925 |doi=10.1245/s10434-013-3129-9 |url=}}</ref><ref name="pmid20422030">{{cite journal |vauthors=Gillen S, Schuster T, Meyer Zum Büschenfelde C, Friess H, Kleeff J |title=Preoperative/neoadjuvant therapy in pancreatic cancer: a systematic review and meta-analysis of response and resection percentages |journal=PLoS Med. |volume=7 |issue=4 |pages=e1000267 |year=2010 |pmid=20422030 |pmc=2857873 |doi=10.1371/journal.pmed.1000267 |url=}}</ref><ref name="pmid22012027">{{cite journal |vauthors=Andriulli A, Festa V, Botteri E, Valvano MR, Koch M, Bassi C, Maisonneuve P, Sebastiano PD |title=Neoadjuvant/preoperative gemcitabine for patients with localized pancreatic cancer: a meta-analysis of prospective studies |journal=Ann. Surg. Oncol. |volume=19 |issue=5 |pages=1644–62 |year=2012 |pmid=22012027 |doi=10.1245/s10434-011-2110-8 |url=}}</ref><ref name="pmid18308215">{{cite journal |vauthors=Greer SE, Pipas JM, Sutton JE, Zaki BI, Tsapakos M, Colacchio TA, Gibson JJ, Wiener DC, Ripple GH, Barth RJ |title=Effect of neoadjuvant therapy on local recurrence after resection of pancreatic adenocarcinoma |journal=J. Am. Coll. Surg. |volume=206 |issue=3 |pages=451–7 |year=2008 |pmid=18308215 |doi=10.1016/j.jamcollsurg.2007.10.002 |url=}}</ref><ref name="pmid12399067">{{cite journal |vauthors=Kim HJ, Czischke K, Brennan MF, Conlon KC |title=Does neoadjuvant chemoradiation downstage locally advanced pancreatic cancer? |journal=J. Gastrointest. Surg. |volume=6 |issue=5 |pages=763–9 |year=2002 |pmid=12399067 |doi= |url=}}</ref><ref name="pmid10487547">{{cite journal |vauthors=Bajetta E, Di Bartolomeo M, Stani SC, Artale S, Ricci SB, Bozzetti F, Mazzaferro V, Toffolatti L, Buzzoni R |title=Chemoradiotherapy as preoperative treatment in locally advanced unresectable pancreatic cancer patients: results of a feasibility study |journal=Int. J. Radiat. Oncol. Biol. Phys. |volume=45 |issue=2 |pages=285–9 |year=1999 |pmid=10487547 |doi= |url=}}</ref>
** Toxic effects of chemotherapy can be tolerated more easily before surgery as compared to after resection.  
** Toxic effects of [[chemotherapy]] can be tolerated more easily before [[surgery]] as compared to after [[resection]].  
** Shrinkage of tumor with neoadjuvant therapy makes resection easier and improves patient prognosis.  
** Shrinkage of [[tumor]] with [[neoadjuvant therapy]] makes resection easier and improves patient prognosis.  
** Systemic treatment for cancer involving various systems improves prognosis.
** Systemic treatment for [[cancer]] involving various systems improves [[prognosis]].
* No therapy is considered as first line therapy under this category.
* No [[therapy]] is considered as first line therapy under this category.
* Decisions for treatment are made on an individual basis.
* Decisions for treatment are made on an individual basis.


=== New Treatments ===
===New Treatments===
Irinotecan in an encapsulated form inside a nanoliposome is being used in advanced pancreatic cancer patients who have been earlier been treated using gemcitabine-based chemotherapy. <ref name="pmid27140876">{{cite journal |vauthors=Chiang NJ, Chang JY, Shan YS, Chen LT |title=Development of nanoliposomal irinotecan (nal-IRI, MM-398, PEP02) in the management of metastatic pancreatic cancer |journal=Expert Opin Pharmacother |volume=17 |issue=10 |pages=1413–20 |year=2016 |pmid=27140876 |doi=10.1080/14656566.2016.1183646 |url=}}</ref>
* [[Irinotecan]] in an encapsulated form inside a nanoliposome is being used in advanced [[pancreatic cancer]] patients who have earlier been treated using [[gemcitabine]]-based [[chemotherapy]].<ref name="pmid27140876">{{cite journal |vauthors=Chiang NJ, Chang JY, Shan YS, Chen LT |title=Development of nanoliposomal irinotecan (nal-IRI, MM-398, PEP02) in the management of metastatic pancreatic cancer |journal=Expert Opin Pharmacother |volume=17 |issue=10 |pages=1413–20 |year=2016 |pmid=27140876 |doi=10.1080/14656566.2016.1183646 |url=}}</ref>
Liposomal Irinotecan is used along with leucovorin and fluorouracil.<ref name="pmid26615328">{{cite journal |vauthors=Wang-Gillam A, Li CP, Bodoky G, Dean A, Shan YS, Jameson G, Macarulla T, Lee KH, Cunningham D, Blanc JF, Hubner RA, Chiu CF, Schwartsmann G, Siveke JT, Braiteh F, Moyo V, Belanger B, Dhindsa N, Bayever E, Von Hoff DD, Chen LT |title=Nanoliposomal irinotecan with fluorouracil and folinic acid in metastatic pancreatic cancer after previous gemcitabine-based therapy (NAPOLI-1): a global, randomised, open-label, phase 3 trial |journal=Lancet |volume=387 |issue=10018 |pages=545–57 |year=2016 |pmid=26615328 |doi=10.1016/S0140-6736(15)00986-1 |url=}}</ref>
* [[Liposome|Liposomal]] [[Irinotecan]] is used along with [[leucovorin]] and [[fluorouracil]].<ref name="pmid26615328">{{cite journal |vauthors=Wang-Gillam A, Li CP, Bodoky G, Dean A, Shan YS, Jameson G, Macarulla T, Lee KH, Cunningham D, Blanc JF, Hubner RA, Chiu CF, Schwartsmann G, Siveke JT, Braiteh F, Moyo V, Belanger B, Dhindsa N, Bayever E, Von Hoff DD, Chen LT |title=Nanoliposomal irinotecan with fluorouracil and folinic acid in metastatic pancreatic cancer after previous gemcitabine-based therapy (NAPOLI-1): a global, randomised, open-label, phase 3 trial |journal=Lancet |volume=387 |issue=10018 |pages=545–57 |year=2016 |pmid=26615328 |doi=10.1016/S0140-6736(15)00986-1 |url=}}</ref>


==References==
==References==
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[[Category:Types of cancer]]
[[Category:Types of cancer]]
[[Category:Mature chapter]]
[[Category:Mature chapter]]
[[Category:Primary care]]
[[Category:Up-To-Date]]
[[Category:Oncology]]
[[Category:Medicine]]
[[Category:Surgery]]
[[Category:Gastroenterology]]

Latest revision as of 23:33, 29 July 2020

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sudarshana Datta, MD [2]

Overview

In patients with pancreatic cancer, surgery is the primary modality of treatment. However, surgery is performed only in a small fraction of patients who have resectable lesions. Majority of patients have unresectable disease and are treated with chemotherapy and/or radiation therapy as a part of adjuvant or neoadjuvant therapy. Curative resection is not performed in cases of extrapancreatic involvement that require palliative therapy. As per the guidelines of The National Comprehensive Cancer Network (NCCN), patients with locally advanced unresectable or metastatic disease should be treated with a combination of Leucovorin, 5-fuorouracil, Oxaliplatin, and Irinotecan also known as FOLFIRINOX regimen. Neoadjuvant therapy is preferred as shrinkage of the tumor using chemotherapy makes resection easier and improves patient prognosis. Radiotherapy may also form part of neoadjuvant therapy to facilitate tumor shrinkage, but its use on unresectable tumors remains controversial.

Medical Therapy

  • New types of treatment such as biologic therapy, are being studied in clinical trials.

Chemotherapy guidelines

  • The National Comprehensive Cancer Network (NCCN) has recommended guidelines for treatment in patients based on their performance status.
  • In order to predict survival of patients in various stages of pancreatic cancer, the performance status of a patient is a major prognostic factor.
  • Patients with poor prognostic factors have poor performance status. This includes:[1]
PREFERRED REGIMENS BASED ON PERFORMANCE STATUS IN LOCALLY ADVANCED/METASTATIC DISEASE
Good perfomance status FOLFIRINOX[15][16][17][18][19][20][21][22][23]
Good perfomance status with intolerance to FOLFIRINOX Paclitaxel protein bound AND Gemcitabine
Poor performance status Gemcitabine monotherapy[24][25][26][27]
Poor performance status refractory to Gemcitabine Capecitabine OR capecitabine AND erlotinib[28]

Preferred regimens based on the stage of pancreatic cancer:

Stages I-II:

Neoadjuvant therapy :

Adjuvant chemotherapy:

  • In patients with resectable pancreatic cancer:
  • Preferred regimen: Gemcitabine 1000 mg/m 2 IV q30min for 3 weeks; every 4 weeks for six cycles

Adjuvant chemotherapy and chemoradiation:

Preferred regimen (1): Gemcitabine 1000 mg/m 2 IV q30min weekly for 3 weeks

Preferred regimen (2): 5-fluorouracil (FU) 250 mg/m 2/day continuous IV infusion via pump

Preferred regimen (3): Radiotherapy 1.8 Gy/day upto a total of 50.4 Gy; then  3-5 wk after chemoradiation: Gemcitabine 1000 mg/m 2 IV q30 min weekly; every 4 weeks for three cycles

Stage III:

Neoadjuvant therapy:

Preferred regimen (1): Gemcitabine 1000 mg/m 2 IV q30 min weekly for 3 weeks, every 4 weeks

Preferred regimen (2): 5-fluorouracil (FU) 500 mg/m 2/day IV bolus on days 1-3 and 29-31 with radiotherapy, 40 Gy

Stage IV:

  • Preferred regimen (1): Protein bound Paclitaxel 125 mg/m 2 AND Gemcitabine 1000 mg/m 2 IV over 30-40 min on days 1, 8, and 15 q4weeks
  • Preferred regimen (2): Gemcitabine 1000 mg/m 2 IV over 30 min q1week for 7 wk, followed by 1 week off, then weekly for 3 wk
  • Preferred regimen (3): Gemcitabine 1000 mg/m 2 IV over 30 min on days 1 and 15 AND  Cisplatin 50 mg/m 2 IV over 1 h on days 1 and 15, q4 weeks
  • Preferred regimen (3): Gemcitabine 1000 mg/m 2 IV weekly for 7 wk AND  Erlotinib 100 mg PO daily on days 1-56 then Gemcitabine 1000 mg/m 2 IV on days 1, 8, and 15 plus  Erlotinib 100 mg PO q24h on days 1-28 in four cycles 
  • Preferred regimen (4): Gemcitabine 1000 mg/m 2 IV weekly for 3 weeks q4weeks AND  Capecitabine 1660 mg/m 2/day weekly for 3 wk; q4weeks
  • Preferred regimen (5): Oxaliplatin 85 mg/m 2 IV AND  Irinotecan 180 mg/m 2 IV on day 1 AND  Leucovorin 400 mg/m 2 IV on day 1, followed by 5-fluorouracil (FU) 400 mg/m 2 IV bolus on day 1 and then 2400 mg/m 2 IV infusion over 46 h on days 1 and 15

Alternative treatment recommendations for Stage IV:

  • Alternative regimen (1): Capecitabine 1250 mg/m 2 PO q12h for 2 weeks, every 3 weeks 
  • Alternative regimen (2): Capecitabine 1000 mg/m 2 PO q12h for 2 weeks; every 3 weeks AND Erlotinib 150 mg PO daily
  • Alternative regimen (3): Irinotecan liposomal 70 mg/m 2 IV infused over 1.5h AND  Leucovorin 400 mg/m 2 IV infused over 30min ,followed by  5-fluorouracil (FU) 2400 mg/m 2 IV infused over 46 h q3 weeks 
  • Alternative regimen (4): 5-fluorouracil (FU) 2000 mg/m 2 IV continuous on days 1, 8, 15, and 22 AND Leucovorin 200 mg/m 2 IV over .5h on days 1, 8, 15, and 22 AND Oxaliplatin 85 mg/m 2 IV on days 8 and 22; q42d

Comparison of one year survival of various regimens is depicted in the table below:

ONE YEAR SURVIVAL OF DIFFERENT REGIMENS
One year survival of FOLFIRINOX (leucovorin AND 5-fluorouracil [LV5-FU] AND oxaliplatin AND Irinotecan) is better than Gemcitabine[16][29][30][31][32][33][34]
One year survival of Gemcitabine AND Erlotinib is better than Gemcitabine[13][35][36]
One year survival of Gemcitabine AND Capecitabine is better than or equal to Gemcitabine [2][37][38][39][40]
One year survival of Gemcitabine AND nanoparticle albumin-bound (nab)-Paclitaxel is better than Gemcitabine[41][42]

Radiation Therapy

Palliative Therapy

Palliative therapy in patients with pancreatic cancer mainly involves the management of symptoms arising as a result of complications of therapy:[47][48][49][50][51][52]

Adjuvant and Neoadjuvant therapy

New Treatments

References

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