Phase II trial of 9-aminocamptothecin administered as a 72-hour continuous infusion in metastatic colorectal carcinoma

Purpose: The camptothecin derivative irinotecan has demonstrated clinical activity in metastatic colorectal carcinoma in both chemotherapy-naive and fluorouracil-refractory patients. 9-Aminocamptothecin (9-AC; NSC 603071), another camptothecin derivative, wets selected for clinical development based on preclinical activity, including cures in human tumor xenografts resistant to standard anticancer agents, We report a phase II trial of 9-AC in patients with previously untreated metastatic colorectal carcinoma. Patients and Methods: Colorectal cancer patients with measurable disease, a performance status of 0 to 2 (Zubrod), and no prior chemotherapy for metastatic disease received 9-AC, A cycle of therapy was 35 mu g/m(2)/h for 72 consecutive hours (840 mu g/m(2)/d for 3 days) and rest on days 4 to 14; a course of therapy was defined as two cycles (28 days), Patients were assessed for response after two courses. Results: Seventeen patients with metastatic colorectal cancer were entered onto this trial, No complete or partial responses were noted, Treatment was well tolerated; toxic effects consisted mainly of neutropenia, nausea, vomiting, stomatitis, fatigue, and anemia, Grade 3 to 4 toxicity was limited to neutropenia (grade 3 in four patients and grade 4 in six), anemia (grade 3 in two patients), and vomiting (grade 3 in two patients). No grade 3 or 4 diarrhea occurred. Only two patients had their 9-AC dose reduced to 30 mu g/m(2)/h, The median nadir absolute granulocyte count (AGC) was 1,500/mu l. The median number of courses given was two and the median time to disease progression was 8 weeks, Conclusion: At the dose and schedule used in this trial, 9-AC lacked antitumor activity in metastatic colorectal cancer, 9-AC infusion schedules of longer duration are currently being investigated in this disease. (C) 1997 by American Society of Clinical Oncology.