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 Phase II study to evaluate the objective tumor response rate of 2 different doses and schedules of 9-aminocamptothecin (9-AC) in previously untreated patients with measurable recurrent metastatic colorectal carcinoma. METHODS. Fifty-one patients were registered. One schedule evaluated 9-AC given at 1100 μg/m²/24 hours by continuous infusion for 72 hours along with granulocyte-colony stimulating factor at 5 μg/kg/day on Days 5 through 12. Another schedule involved 9-AC at 480 μg/m²/24 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 received 72-hour infusion and 20 patients who received 120-hour infusion) for response and toxicity. Significant hematologic toxicities were encountered, especially with the 72-hour infusion schedule, in which 43% (12 of 28) and 28% (8 of 28) experienced Grade 4 (National Cancer Institute Common Toxicity Criteria) leukopenia and thrombocytopenia, respectively. Grade 4 neutropenia was encountered in 61% (17 of 28) and 11% (2 of 19) of patients on the 72-hour and 120-hour infusion schedules, respectively. Diarrhea, nausea, vomiting, and hepatotoxicity were troublesome nonhematologic toxicities. Seventy-nine percent (11 of 14) and 57% (4 of 7) of the patients experiencing Grade 3 or 4 nonhematologic toxicity were on the 72-hour infusion schedule. Three patients died of chemotherapy-related toxicity. One response was observed in 48 evaluable patients (2%). CONCLOSIONS. 9-AC did not demonstrate sufficient antitumor activity and had unacceptable toxicity in previously untreated patients with metastatic colorectal carcinoma. (C) 2000 American Cancer Society.