CPT-11 : an analog of Camptothecin in early clinical development

CPT-11 is a water-soluble analog of camptothecin synthesized by Yakult Honsha Co. Ltd (Japan). CPT-11 and its main metabolite SN-38 are active against a variety of human cancer cell lines, even in resistant cell lines [1], as well as in murine tumor models [2]. Their mechanism of action is presumed to be through inhibition of Topolsomerase I. A previous Japanese Phase I study of CPT-11 established the MDT at 250 mg/m2 as a single dose. The dose limiting toxicity was leukopenia with mild anemia and thrombocytopenia [3]. The recommended dose for Phase II trials was 200 mg/m2 every 3 weeks. Phase II trials started in Japan with different therapeutic schedules, and showed interesting response rates in lung cancers and others tumors including colorectal, gastric, cervical, ovarian [4,5] and hematological malignancies [6].