Camptothecin delivery systems: the antitumor activity of a camptothecin-20-0-polyethylene glycol ester transport form

This study was designed to assess the efficacy of polyethylene glycol(PEG) conjugated camptothecin, PEG-alpha-camptothecin, a novel water soluble transport form (prodrug) of the naturally derived antitumor drug, 20-(S)-camptothecin.

Circulatory retention studies were performed in non-tumor bearing mice injected intravenously with 300 mg/kg of PEG-alpha-camptothecin. Therapeutic efficacy was evaluated in both a murine P388/0 leukemia and a colorectal HT-29 carcinoma xenograft model.

PEG-alpha-camptothecin had a blood t1/2 alpha of less than 5 minutes and a t1/2 beta of 3.5 hours. Five intraperitoneal injections of 3.2 mg/kg/day 20-(S)-camptothecin equivalents of PEG-alpha-camptothecin in our leukemia model resulted in significant survival over untreated controls (P < 0.001), with a mean time to death of treated versus control (T/C ratio) of 2.94 and a cure rate of 80% (n = 20). The colorectal carcinoma xenograft model demonstrated that 2-3 mg/kg/day 20-(S)-camptothecin equivalents of PEG-alpha-camptothecin given 5 days a week for 5 weeks could reduce an initial tumor burden of 300 mm3 by more than 90% without any signs of overt toxicity.

This water soluble transport form of 20-(S)-camptothecin and its underlying technology may have clinical application.