Leiomyosarcoma medical therapy: Difference between revisions

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{{Leiomyosarcoma}}
{{Leiomyosarcoma}}
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==Overview==
==Overview==


Patients with leiomyosarcoma have many treatment options. The selection depends on the stage of the tumor. The options are surgery, radiation therapy, chemotherapy, or a combination of these methods. Before treatment starts, ask your health care team about possible side effects and how treatment may change your normal activities. Because cancer treatments often damage healthy cells and tissues, side effects are common. Side effects may not be the same for each person, and they may change from one treatment session to the next.Non surgical treatment options have shown only limited benefit in the treatment of the Leiomyosarcoma and are generally considered to be less responsive of chemotherapy and radiotherapy.It has generally noted that only 40% cases responds to the chemotherapeutic regimens.
[[Uterine]] leiomyosarcoma (LMS) is the most common [[sarcoma]] arising from the [[uterus]] and comprises approximately 2% of uterine cancers. Patients diagnosed with LMS have a 5-year overall survival ranging from 25-75% . The primary management of LMS is [[hysterectomy]]. [[Adjuvant]] [[pelvic]] [[radiotherapy]] has been shown to improve local control and survival of patients with leiomyosarcoma.  


==Chemotherapy==
==Chemotherapy==
*'''Chemotherapy:''' The treatment is to use drugs to stop the growth of cancer cells either by killing the cells or by stopping them from dividing. Usual drugs include ifosfamide and doxorubicin (Adriamycin).
*'''[[Chemotherapy]]''' is recommended for individuals who have locally advanced, [[metastatic]], or recurrent disease. Usually in combination with surgical procedures and/or radiation. The treatment is to use drugs to stop the growth of cancer [[cells]] either by killing the cells or by stopping them from dividing.<ref name="InHu2017">{{cite journal|last1=In|first1=Gino K.|last2=Hu|first2=James S.|last3=Tseng|first3=William W.|title=Treatment of advanced, metastatic soft tissue sarcoma: latest evidence and clinical considerations|journal=Therapeutic Advances in Medical Oncology|volume=9|issue=8|year=2017|pages=533–550|issn=1758-8340|doi=10.1177/1758834017712963}}</ref><ref name="pmid29768050">Blay JY (2018) [https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=29768050 Getting up-to-date in the management of soft tissue sarcoma.] ''Future Oncol'' 14 (10s):3-13. [http://dx.doi.org/10.2217/fon-2018-0074 DOI:10.2217/fon-2018-0074] PMID: [https://pubmed.gov/29768050 29768050]</ref><ref name="pmid5778386">(1969) [https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=5778386 New antiviral drug.] ''Nature'' 222 (5190):218. PMID: [https://pubmed.gov/5778386 5778386]</ref>
*[[Anthracyclines]] stops the [[tumor]] growth by different mechanism such as intercalating into [[deoxyribonucleic acid]] ([[DNA]]), blocking [[DNA]] and [[ribonucleic acid]] ([[RNA]]) [[synthesis]], also causing [[DNA]] breakage by interfering with [[topoisomerase II]] activity. 
*Most common drugs used as first line treatment of soft tissue [[sarcoma]] include combination of [[ifosfamide]] and [[doxorubicin]] ([[Adriamycin]]).  
*[[Surgical]] resection of localized disease is a mainstay [[therapeutic]] strategy.
*In the event tumors have metastasized or spread beyond [[uterus]] and not resectable by [[surgery]], [[cytotoxic]] [[chemotherapeutic agents]] can be used in combination with [[radiation therapy]].
*Some of these [[chemotherapeutic agents]] are [[gemcitabine]], [[docetaxel]], [[ifosfamide]], [[temozolomide]], [[trabectedin]], [[eribulin]].
 
 
*'''Regimen includes the following:'''<ref name="pmid12910529">{{cite journal |vauthors=Laverdiere C, Kolb EA, Supko JG, Gorlick R, Meyers PA, Maki RG, Wexler L, Demetri GD, Healey JH, Huvos AG, Goorin AM, Bagatell R, Ruiz-Casado A, Guzman C, Jimeno J, Harmon D |title=Phase II study of ecteinascidin 743 in heavily pretreated patients with recurrent osteosarcoma |journal=Cancer |volume=98 |issue=4 |pages=832–40 |date=August 2003 |pmid=12910529 |doi=10.1002/cncr.11563 |url=}}</ref><ref name="pmid15084621">{{cite journal |vauthors=Garcia-Carbonero R, Supko JG, Manola J, Seiden MV, Harmon D, Ryan DP, Quigley MT, Merriam P, Canniff J, Goss G, Matulonis U, Maki RG, Lopez T, Puchalski TA, Sancho MA, Gomez J, Guzman C, Jimeno J, Demetri GD |title=Phase II and pharmacokinetic study of ecteinascidin 743 in patients with progressive sarcomas of soft tissues refractory to chemotherapy |journal=J. Clin. Oncol. |volume=22 |issue=8 |pages=1480–90 |date=April 2004 |pmid=15084621 |doi=10.1200/JCO.2004.02.098 |url=}}</ref><ref name="pmid16110008">{{cite journal |vauthors=Garcia-Carbonero R, Supko JG, Maki RG, Manola J, Ryan DP, Harmon D, Puchalski TA, Goss G, Seiden MV, Waxman A, Quigley MT, Lopez T, Sancho MA, Jimeno J, Guzman C, Demetri GD |title=Ecteinascidin-743 (ET-743) for chemotherapy-naive patients with advanced soft tissue sarcomas: multicenter phase II and pharmacokinetic study |journal=J. Clin. Oncol. |volume=23 |issue=24 |pages=5484–92 |date=August 2005 |pmid=16110008 |doi=10.1200/JCO.2005.05.028 |url=}}</ref><ref name="pmid11870176">{{cite journal |vauthors=Lopez M, Vici P, Di Lauro L, Carpano S |title=Increasing single epirubicin doses in advanced soft tissue sarcomas |journal=J. Clin. Oncol. |volume=20 |issue=5 |pages=1329–34 |date=March 2002 |pmid=11870176 |doi=10.1200/JCO.2002.20.5.1329 |url=}}</ref>
*[[Doxorubicin]] 60 mg/m2 every 3 wk; doses as high as 75 mg/m2 can be given; however, this can be administered as a split dose over 3 d (25 mg/m2/day for 3 d); maximum lifetime dose is 475-600 mg/m2 or
 
*[[Liposomal]] pegylated [[doxorubicin]]: doses as high as 50 mg/m2 every 4 wk have been used in clinical trials; however, this is associated with significant [[toxicity]]; commonly used doses include 30-35 mg/m2 every 4 wk; no maximum lifetime doses or
 
*[[Ifosfamide]] 2000-3000 mg/m2/day IV over 3 h for 3-4 d plus [[mesna]]; repeat every 21 d or
 
*[[Ifosfamide]] 5000 mg/m2 over 24 h plus  [[mesna]] 5000 mg/m2 over 24 h and an additional 400-600 mg/m2 for 2 h after completion of [[ifosfamide]]; repeat every 21 d (European schedule) or
 
*[[Gemcitabine]] 1200 mg/m2 IV over 90-120min on days 1 and 8; repeat cycle every 21d or
 
*[[Trabectedin]] 1.5 mg/m2 IV q3wk until [[disease]] progression or unacceptable [[toxicity]]; premedication require and infuse via central line over 24h
*[[Epirubicin]] 160 mg/m2 IV [[bolus]] every 3 wk with [[growth factor]] support or
 
*[[Dacarbazine]] 250 mg/m2 IV for 5 d or 800-1000 mg/m2 IV every 3 wk or
 
*[[Pazopanib]] 800 mg PO qd (not indicated for [[liposarcoma]] outside of a clinical trial; [[FDA]] approved as second-line [[chemotherapy]]; recommend starting at a low dose of 200 mg for 2 weeks and slowly increasing the dose)


==Radiation Therapy==
==Radiation Therapy==
*'''Radiation therapy:''' This is a cancer treatment to kill cancer cells or keep them from growing by using high-energy x-rays or other types of radiation.Radiotherapy may be a useful adjunct to improve local control or where a cancer is inoperable due to the specific location or possible progression of the malignancy.It can be used postoperative to help treat known or possible residual disease.
* '''[[Radiation therapy]]''' may be a useful adjunct to improve local control or where a cancer is inoperable due to the specific location or possible progression of the malignancy.<ref name="SampathGaffney2011">{{cite journal|last1=Sampath|first1=Sagus|last2=Gaffney|first2=David K.|title=Role of radiotherapy treatment of uterine sarcoma|journal=Best Practice & Research Clinical Obstetrics & Gynaecology|volume=25|issue=6|year=2011|pages=761–772|issn=15216934|doi=10.1016/j.bpobgyn.2011.06.004}}</ref>
* It can be used postoperative to help treat known or possible residual disease. [[Radiation therapy]] can also be used as a [[palliative care]] in cases where extensive [[metastasis]] has already occurred.<ref name="pmid18378136">Reed NS, Mangioni C, Malmström H, Scarfone G, Poveda A, Pecorelli S et al. (2008) [https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=18378136 Phase III randomised study to evaluate the role of adjuvant pelvic radiotherapy in the treatment of uterine sarcomas stages I and II: an European Organisation for Research and Treatment of Cancer Gynaecological Cancer Group Study (protocol 55874).] ''Eur J Cancer'' 44 (6):808-18. [http://dx.doi.org/10.1016/j.ejca.2008.01.019 DOI:10.1016/j.ejca.2008.01.019] PMID: [https://pubmed.gov/18378136 18378136]</ref>
 
* [[Adjuvant]] [[pelvic]] [[radiotherapy]] has been shown by some to improve disease-free survival. <ref name="HarryNarayansingh2007">{{cite journal|last1=Harry|first1=Vanessa N|last2=Narayansingh|first2=Gordon V|last3=Parkin|first3=David E|title=Uterine leiomyosarcomas: a review of the diagnostic and therapeutic pitfalls|journal=The Obstetrician & Gynaecologist|volume=9|issue=2|year=2007|pages=88–94|issn=14672561|doi=10.1576/toag.9.2.088.27309}}</ref>
 
* Studies had shown that there is a 38% disease-free [[survival rate]] in women receiving [[adjuvant]] [[radiotherapy]] compared with 18% in women receiving surgery alone.<ref name="HarryNarayansingh20072">{{cite journal|last1=Harry|first1=Vanessa N|last2=Narayansingh|first2=Gordon V|last3=Parkin|first3=David E|title=Uterine leiomyosarcomas: a review of the diagnostic and therapeutic pitfalls|journal=The Obstetrician & Gynaecologist|volume=9|issue=2|year=2007|pages=88–94|issn=14672561|doi=10.1576/toag.9.2.088.27309}}</ref>


==Palliative treatment==
==Novel therapies==
*'''Palliative treatment:''' This treatment is used for the patients whose cancer has spread. It may improve the patient's quality of life by controlling the symptoms and complications of this disease.
Studies have shown that some of the sarcomas express [[angiogenic]] factors, such as [[vascular endothelial growth factor]], therefore the use of anti‐angiogenic agents is reasonable as part of the treatment on case basis.<ref name="BoyarHesdorffer2008">{{cite journal|last1=Boyar|first1=Michelle S.|last2=Hesdorffer|first2=Mary|last3=Keohan|first3=Mary Louise|last4=Jin|first4=Zhezhen|last5=Taub|first5=Robert N.|title=Phase II Study of Temozolomide and Thalidomide in Patients with Unresectable or Metastatic Leiomyosarcoma|journal=Sarcoma|volume=2008|year=2008|pages=1–7|issn=1357-714X|doi=10.1155/2008/412503}}</ref>


:* [[Thalidomide]], an [[angiogenesis inhibitor]], is currently being investigated to be used for the treatment of leiomyosarcoma.
==References==
==References==
{{reflist|2}}
{{reflist|2}}

Latest revision as of 15:54, 4 April 2019

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Nima Nasiri, M.D.[2]

Overview

Uterine leiomyosarcoma (LMS) is the most common sarcoma arising from the uterus and comprises approximately 2% of uterine cancers. Patients diagnosed with LMS have a 5-year overall survival ranging from 25-75% . The primary management of LMS is hysterectomy. Adjuvant pelvic radiotherapy has been shown to improve local control and survival of patients with leiomyosarcoma.

Chemotherapy


  • Regimen includes the following:[4][5][6][7]
  • Doxorubicin 60 mg/m2 every 3 wk; doses as high as 75 mg/m2 can be given; however, this can be administered as a split dose over 3 d (25 mg/m2/day for 3 d); maximum lifetime dose is 475-600 mg/m2 or
  • Liposomal pegylated doxorubicin: doses as high as 50 mg/m2 every 4 wk have been used in clinical trials; however, this is associated with significant toxicity; commonly used doses include 30-35 mg/m2 every 4 wk; no maximum lifetime doses or
  • Ifosfamide 2000-3000 mg/m2/day IV over 3 h for 3-4 d plus mesna; repeat every 21 d or
  • Ifosfamide 5000 mg/m2 over 24 h plus mesna 5000 mg/m2 over 24 h and an additional 400-600 mg/m2 for 2 h after completion of ifosfamide; repeat every 21 d (European schedule) or
  • Gemcitabine 1200 mg/m2 IV over 90-120min on days 1 and 8; repeat cycle every 21d or
  • Dacarbazine 250 mg/m2 IV for 5 d or 800-1000 mg/m2 IV every 3 wk or
  • Pazopanib 800 mg PO qd (not indicated for liposarcoma outside of a clinical trial; FDA approved as second-line chemotherapy; recommend starting at a low dose of 200 mg for 2 weeks and slowly increasing the dose)

Radiation Therapy

  • Radiation therapy may be a useful adjunct to improve local control or where a cancer is inoperable due to the specific location or possible progression of the malignancy.[8]
  • It can be used postoperative to help treat known or possible residual disease. Radiation therapy can also be used as a palliative care in cases where extensive metastasis has already occurred.[9]

Novel therapies

Studies have shown that some of the sarcomas express angiogenic factors, such as vascular endothelial growth factor, therefore the use of anti‐angiogenic agents is reasonable as part of the treatment on case basis.[12]

References

  1. In, Gino K.; Hu, James S.; Tseng, William W. (2017). "Treatment of advanced, metastatic soft tissue sarcoma: latest evidence and clinical considerations". Therapeutic Advances in Medical Oncology. 9 (8): 533–550. doi:10.1177/1758834017712963. ISSN 1758-8340.
  2. Blay JY (2018) Getting up-to-date in the management of soft tissue sarcoma. Future Oncol 14 (10s):3-13. DOI:10.2217/fon-2018-0074 PMID: 29768050
  3. (1969) New antiviral drug. Nature 222 (5190):218. PMID: 5778386
  4. Laverdiere C, Kolb EA, Supko JG, Gorlick R, Meyers PA, Maki RG, Wexler L, Demetri GD, Healey JH, Huvos AG, Goorin AM, Bagatell R, Ruiz-Casado A, Guzman C, Jimeno J, Harmon D (August 2003). "Phase II study of ecteinascidin 743 in heavily pretreated patients with recurrent osteosarcoma". Cancer. 98 (4): 832–40. doi:10.1002/cncr.11563. PMID 12910529.
  5. Garcia-Carbonero R, Supko JG, Manola J, Seiden MV, Harmon D, Ryan DP, Quigley MT, Merriam P, Canniff J, Goss G, Matulonis U, Maki RG, Lopez T, Puchalski TA, Sancho MA, Gomez J, Guzman C, Jimeno J, Demetri GD (April 2004). "Phase II and pharmacokinetic study of ecteinascidin 743 in patients with progressive sarcomas of soft tissues refractory to chemotherapy". J. Clin. Oncol. 22 (8): 1480–90. doi:10.1200/JCO.2004.02.098. PMID 15084621.
  6. Garcia-Carbonero R, Supko JG, Maki RG, Manola J, Ryan DP, Harmon D, Puchalski TA, Goss G, Seiden MV, Waxman A, Quigley MT, Lopez T, Sancho MA, Jimeno J, Guzman C, Demetri GD (August 2005). "Ecteinascidin-743 (ET-743) for chemotherapy-naive patients with advanced soft tissue sarcomas: multicenter phase II and pharmacokinetic study". J. Clin. Oncol. 23 (24): 5484–92. doi:10.1200/JCO.2005.05.028. PMID 16110008.
  7. Lopez M, Vici P, Di Lauro L, Carpano S (March 2002). "Increasing single epirubicin doses in advanced soft tissue sarcomas". J. Clin. Oncol. 20 (5): 1329–34. doi:10.1200/JCO.2002.20.5.1329. PMID 11870176.
  8. Sampath, Sagus; Gaffney, David K. (2011). "Role of radiotherapy treatment of uterine sarcoma". Best Practice & Research Clinical Obstetrics & Gynaecology. 25 (6): 761–772. doi:10.1016/j.bpobgyn.2011.06.004. ISSN 1521-6934.
  9. Reed NS, Mangioni C, Malmström H, Scarfone G, Poveda A, Pecorelli S et al. (2008) Phase III randomised study to evaluate the role of adjuvant pelvic radiotherapy in the treatment of uterine sarcomas stages I and II: an European Organisation for Research and Treatment of Cancer Gynaecological Cancer Group Study (protocol 55874). Eur J Cancer 44 (6):808-18. DOI:10.1016/j.ejca.2008.01.019 PMID: 18378136
  10. Harry, Vanessa N; Narayansingh, Gordon V; Parkin, David E (2007). "Uterine leiomyosarcomas: a review of the diagnostic and therapeutic pitfalls". The Obstetrician & Gynaecologist. 9 (2): 88–94. doi:10.1576/toag.9.2.088.27309. ISSN 1467-2561.
  11. Harry, Vanessa N; Narayansingh, Gordon V; Parkin, David E (2007). "Uterine leiomyosarcomas: a review of the diagnostic and therapeutic pitfalls". The Obstetrician & Gynaecologist. 9 (2): 88–94. doi:10.1576/toag.9.2.088.27309. ISSN 1467-2561.
  12. Boyar, Michelle S.; Hesdorffer, Mary; Keohan, Mary Louise; Jin, Zhezhen; Taub, Robert N. (2008). "Phase II Study of Temozolomide and Thalidomide in Patients with Unresectable or Metastatic Leiomyosarcoma". Sarcoma. 2008: 1–7. doi:10.1155/2008/412503. ISSN 1357-714X.


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