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]

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