Appendix cancer medical therapy

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

Overview

Medical therapy in appendix cancer could be either supportive, palliative, or curative. While carcinoid tumors rarely need chemotherapy, systemic chemotherapy as well as hyperthermic intraperitoneal chemotherapy plus/minus early postoperative intraperitoneal chemotherapy (EPIC) and/or concomitant intravenous chemotherapy are main stem of chemotherapy in adenocarcinoma of appendix. Medical therapy is generally administered to control the symptoms in patients with carcionid tumors and carcinoid syndrome.

Medical Therapy

• Supportive medical therapy for appendix cancer, may include:

• Somatostatin analogs

• Octreotide or lanreotide

• Loperamide or diphenoxylate for primary diarrhea
• Somatostatin analogs for symptom control in patients with carcionid syndrome

• Curative and palliative chemotherapy

• Systemic chemotherapy
• Hyperthermic intraperitoneal chemotherapy

• Systemic chemotherapy
• Systemic chemotherapy has not been generally recommended for carcionid tumors, but patients with noncacinoid tumors are usually receive chemotherapy.

• Nevertheless systemic chemotherapy for metastatic appendiceal adenocarcinoma has not been studied appropriately
• Many experts refer to current colorectal cancer chemotherapy approaches for adenocarcinoma of appendix
• Current colon cancer chemotherapy agents

• 5-fluorouracil (5-FU) : Traditional active agent
• Irinotecan
• Oxaliplatin
• Vascular endothelial growth factor receptor inhibitors (bevacizumab)
• Epidermal growth factor receptor inhibitors (cetuximab and panitumumab),
• Aflibercept
• Regorafenib: inhibitor of angiogenic tyrosine kinases (including the VEGF receptors 1,2, and 3),
• Capecitabine or 5-FU with or without a platinum drug

• FOLFOX6 has been widely recommended in patients with appendix adenocarcinoma.

• Oxaliplatin, 5-FU and leucovorin or Capecitabine are active agents of the FOLFOX regime. Please see below for the details of FOlFOX6 <math>\blacktriangledown</math>

Modified FOLFOX6
Oxaliplatin 85 mg/m 2 IV Dilute with 250 mL 5 percent dextrose in water (D5W) Administer over 2 hrs Avoid extravasation: May cause significant tissue damage
Leucovorin 400 mg/m 2 IV (d,l-racemic mixture) / 200 mg/m 2 IV (l-leucovorin) Dilute with 250 mL D5W Administer over 2 hrs concurrent with oxaliplatin.
Fluorouracil (FU) 400 mg/m 2 IV bolus Slow IV push over 5 mins (administer immediately after leucovorin)
Fluorouracil (FU) 2400 mg/m 2 IV Administer immediately after FU IV bolus Dilute with 500 to 1000 mL D5W Administer over 46 hours

• Cycle length 14 days
• Doses should be recalculated if there is a 10 percent or more change in body weight.

• Prior to each treatment<math>\blacktriangledown</math>

• Assess changes in neurologic function
• Assess electrolytes and liver and renal function
• CBC with differential and platelet count

• Common complications and approaches to complications

• Diarrhea:

• Grade 2 or worse diarrhea <math>\blacktriangledown</math>
  • Withhold treatment
  • Restart at a lower dose of FU after complete resolution
• Severe diarrhea, mucositis, and myelosuppression after FU <math>\blacktriangledown</math>
  • Evaluate for dihydropyrimidine dehydrogenase deficiency

• Neurologic toxicity

• In order to decrease chance of developing Oxaliplatin induced neuropathy recommend patients to avoid exposure to cold up to 48 hours after each infusion.
• Transient grade 3 paresthesias/dysesthesias / grade 2 symptoms lasting longer than 1 week<math>\blacktriangledown</math>
  • Decrease oxaliplatin dose by 25 percent.
• Grade 4 or persistent grade 3 paresthesia/dysesthesia<math>\blacktriangledown</math>
  • Discontinue oxaliplatin

• Myelotoxicity

• Total white blood cell count <3000 cells/mm ³ , absolute neutrophil count <1500 cells/mm ³ , or platelets <100,000 /mm ³ on the day of treatment<math>\blacktriangledown</math>
  • Delay treatment cycle by one week
• If treatment is delayed for two weeks or delayed for one week on two separate occasions, eliminate FU bolus
• If occurred again<math>\blacktriangledown</math>

• Reduce infusional FU by 20 percent and
• Reduce oxaliplatin dose from 65 mg/m ²

• Hyperthermic intraperitoneal chemotherapy

• Delivered in the operating room after cytoreductive surgery
• in selected cases is accompanied by early postoperative intraperitoneal chemotherapy (EPIC) as well as Concomitant intravenous chemotherapy (CIVC).

Common HIPEC current regimens
Oxaliplatin, 130 mg/m 2 for 60 minutes Concomitant intravenous chemotherapy (CIVC) 5-FU, 400 mg/m 2 Early postoperative intraperitoneal chemotherapy (EPIC) with 5-FU
Mitomycin C, 35 mg/m 2 for 90 minutes Concomitant intravenous chemotherapy 5-FU, 400 mg/m 2 Early postoperative intraperitoneal chemotherapy (EPIC) with 5-FU
Mitomycin C, 35 mg/m 2 for 90 minutes without EPIC or CIVC
Mitomycin C, 3.3 mg//m 2/L for 90 minutes without EPIC or CIVC

• Infuse the fluid at 43-45°Ci n order to maintain the intraperitoneal fluid temperature at 41-43°C
• To avoid renal toxicity maintain urine output higher than 100 cc (desirable 150 cc) every 15 min during HIPEC