PHASE-I TRIAL OF SULINDAC PLUS 5-FLUOROURACIL AND LEVAMISOLE - POTENTIAL ADJUVANT THERAPY FOR COLON-CARCINOMA

Epidemiological studies indicate that nonsteroidal antiinflammatory ag ents may reduce colorectal cancer incidence and mortality, Moreover, s ulindac has been shown to attenuate the growth and progression of colo nic neoplasms in an experimental model of colon carcinoma and in patie nts with familial adenomatous polyposis, To determine whether sulindac (300 mg/day) would increase toxicity associated with 5-fluorouracil ( 5-FU) and levamisole, 15 patients with advanced colorectal cancer were treated. Median treatment duration was 3 (range, 0.6-6.0) months, and median age was 56 years (33% greater than or equal to 60 years), All patients had failed prior 5-FU-based therapy, had measurable disease, and were evaluable for toxicity, Grade III/IV granulocytopenia occurre d in four patients; three patients had received prior pelvic irradiati on resulting in a predisposition to myelosuppression, Two patients dev eloped grade III anemia, and occult gastrointestinal bleeding was susp ected in one, No other grade II or greater gastrointestinal or other n onhematological toxicity occurred, One patient had a partial response, 3 patients had disease stabilization, and 10 patients progressed on s tudy, Our results indicate that sulindac does not significantly increa se short-term toxicity associated with 5-FU and levamisole. To determi ne whether sulindac increases the efficacy of adjuvant chemotherapy, w e propose a phase III randomized trial in patients with lymph nodeposi tive colon cancer.