A north central cancer treatment group phase II trial of 9-aminocamptothecin in previously untreated patients with measurable metastatic colorectal carcinoma

BACKGROUND. Topoisomerase I inhibitors have demonstrated clinical activity in patients with metastatic colorectal carcinoma. The authors performed a P hase II study to evaluate the objective tumor response rate of 2 different doses and schedules of 9-aminocamptothecin (9-AC) in previously untreated p atients with measurable recurrent metastatic colorectal carcinoma. METHODS. Fifty-one patients were registered. One schedule evaluated 9-AC gi ven at 1100 mu g/m(2)/24 hours by continuous infusion for 72 hours along wi th granulocyte-colony stimulating factor at 5 mu g/kg/day on Days 5 through 12. Another schedule involved 9-AC at 480 mu g/m(2)/24 hours by continuous infusion for 120 hours on Days 1, 8, and 15 given every 4 weeks. RESULTS, Forty-eight of 51 patients (94%) were evaluable (28 patients who r eceived 72-hour infusion and 20 patients who received 120-hour infusion) fo r response and toxicity. Significant hematologic toxicities were encountere d, especially with the 72-hour infusion schedule, in which 43% (12 of 28) a nd 28% (8 of 28) experienced Grade 4 (National Cancer Institute Common Toxi city Criteria) leukopenia and thrombocytopenia, respectively. Grade 4 neutr openia was encountered in 61% (17 of 28) and 11% (2 of 19) of patients on t he 72-hour and 120-hour infusion schedules, respectively. Diarrhea, nausea, vomiting, and hepatotoxicity were troublesome nonhematologic toxicities. S eventy-nine percent (11 of 14) and 57% (4 of 7) of the patients experiencin g Grade 3 or 4 nonhematologic toxicity were on the 72-hour infusion schedul e. Three patients died of chemotherapy-related toxicity. One response was o bserved in 48 evaluable patients (2%). CONCLUSIONS. 9-AC did not demonstrate sufficient antitumor activity and had unacceptable toxicity in previously untreated patients with metastatic col orectal carcinoma. Cancer 2000;89:1699-705. (C) 2000 American Cancer Societ y.