octreotide in preventing or reducing diarrhea in patients receiving chemoradiotherapy for anal or rectal cancer

Conditions: Anal Cancer; Colorectal Cancer; Drug/Agent Toxicity by Tissue/Organ; Radiation Enteritis

Summary: rationale: octreotide may be effective in preventing or controlling diarrhea in patients who are undergoing chemoradiotherapy for anal or rectal cancer. it is not yet known whether octreotide is effective in treating diarrhea. purpose: this randomized phase iii trial is studying octreotide in preventing or reducing diarrhea in patients who are undergoing chemoradiotherapy for anal or rectal cancer.

objectives: primary * determine the ability of octreotide to prevent the incidence of moderate, severe, or life-threatening chemoradiotherapy-induced diarrhea (grades 2-4) in patients with anal or rectal cancer. secondary * compare the quality of life of patients treated with this drug vs placebo. * compare the number of hospitalizations and use of antidiarrheal agents (e.g., imodium®) related to diarrhea (or its complications) in patients treated with these drugs. * compare treatment delays and/or dose reductions (chemotherapy and radiotherapy) in patients treated with these drugs. outline: this is a double-blind, placebo-controlled, randomized, multicenter study. patients are stratified according to radiotherapy dose (\< 50 gy vs ≥ 50 gy), chemotherapy dose (bolus vs continuous), and gender. patients are randomized to 1 of 2 treatment arms. * arm i: patients receive octreotide\* intramuscularly (im) 4-7 days before the start of chemoradiotherapy and on day 22 (± 3 days) during chemoradiotherapy. * arm ii: patients receive placebo\* im 4-7 days before the start of chemoradiotherapy and on day 22 (± 3 days) during chemoradiotherapy. note: \*patients receive a total of 2 injections of octreotide or placebo in both arms, treatment continues in the absence of unacceptable toxicity. quality of life is assessed at baseline, at the completion of chemoradiotherapy, and at 3, 6, 9, and 15 months from the start of chemoradiotherapy. patients are followed at 3, 6, 9, and 15 months from the start of chemoradiotherapy. projected accrual: a total of 226 patients (113 per treatment arm) will be accrued for this study within 2 years.

Eligibility criteria:
disease characteristics: * histologically confirmed primary anal or rectal cancer * no metastasis beyond the pelvic regional nodes * must be scheduled to receive chemoradiotherapy patient characteristics: age * 18 and over performance status * not specified life expectancy * not specified hematopoietic * not specified hepatic * liver function tests \< 3 times upper limit of normal * no prior hepatic disease renal * not specified gastrointestinal * no prior chronic or acute regional enteritis * no malabsorption syndrome * no prior inflammatory bowel disease that may exacerbate the radiotherapy toxicity * no grade 2 or greater uncontrollable diarrhea at baseline * no prior cholecystitis or gallstones, unless a cholecystectomy has been performed * no prior incontinence of stool other * not pregnant or nursing * negative pregnancy test * fertile patients must use effective contraception * hiv negative * no uncontrolled diabetes (e.g., fasting glucose \> 250 mg/dl) * no prior allergy or hypersensitivity to study drug or other related drug or compound * no other medical condition or mental impairment that would preclude study treatment and compliance prior concurrent therapy: biologic therapy * not specified chemotherapy * see disease characteristics * prior chemotherapy allowed endocrine therapy * at least 6 months since prior administration of any of the following: * glucocorticoid therapy * insulin sensitizers (e.g., metformin, pioglitazone, or rosiglitazone) * exogenous growth hormone therapy radiotherapy * see disease characteristics * no prior pelvic radiotherapy * no prior intensity-modulated radiotherapy * no concurrent radiotherapy for abdominal cancer * no concurrent hyperfractionated, split-course, or intensity-modulated radiotherapy * no brachytherapy prior to or after completion of all external beam radiotherapy surgery * no prior abdominal-perineal resection or other surgical procedure leaving the patient without a functioning rectum * no colostomy other * more than 30 days since other prior investigational drugs * no prior octreotide for cancer therapy-related diarrhea * no concurrent prophylactic antidiarrheal medication

Keywords: radiation enteritis drug/agent toxicity by tissue/organ stage i rectal cancer stage ii rectal cancer stage iii rectal cancer stage iiia anal cancer stage iiib anal cancer recurrent anal cancer stage i anal cancer stage ii anal cancer recurrent rectal cancer