Abstract:

9-Aminocamptothecin (9-AC) is a camptothecin derivative with broad antitumor activity in preclinical studies. Prior investigations suggested that prolonged maintenance of 9-AC lactone plasma concentrations above 10 nmol/l and frequent administration of the drug are important determinants of antitumor activity. Our phase II study, therefore, examined a 5-day continuous infusion of 9-AC weekly for 3 weeks in patients with advanced colorectal cancer. Eighteen patients previously untreated for metastatic disease received 480 g/m^2/day of 9-AC. No responses were observed in 17 evaluable patients. Severe toxicities included granulocytopenia, nausea, vomiting and diarrhea. The median absolute granulocyte count (AGC) nadir was 2,300/l (range 0–9,000/l) and occurred on day 10. Eight patients received an escalated dose of 600 g/m^2/day. The median AGC nadir at the escalated dose was 1,500/l (range: 300–2,700/l) and occurred on day 22. The median number of courses given was 2 (range: 1–8); and the median time to disease progression was 8 weeks (range: 1–40 weeks). 9-AC administered by this schedule lacked antitumor activity in patients with advanced colorectal carcinomas.

Keywords: 9-AC; 9-aminocamptothecin; camptothecin; colorectal cancer; phase II

Language: English

Document Type: Regular paper

Affiliations: 1: Division of Medicine, University of Texas M.D. Anderson Cancer Center, Houston, TX 2: Wichita CCOP, Wichita, KS 3: Syracuse CCOP, Syracuse, NY 4: Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, MD, USA