Cisplatin and irinotecan in upper gastrointestinal malignancies

Irinotecan (CPT-11, Camptosar) a topoisomerase I inhibitor derived from the Chinese shrub Camptotheca acuminata, has broad activity in varied gastrointestinal malignancies, including pancreatic, biliary, esophageal, and stomach cancers. Using cisplatin (Platinol) plus irinotecan as a backbone for chemotherapy, a combination for which in vitro synergy and possible sequence dependency have been identified, several clinical trials are being conducted combining these two drugs with other chemotherapeutic agents and radiation. This article reviews a recently reported phase II study of cisplatin and irinotecan in esophageal cancer, and provides a preliminary report of two ongoing phase I studies of cisplatin/irinotecan/paclitaxel (Taxol); and cisplatin/irinotecan/fluorouracil (5-FU) in advanced gastrointestinal malignancies. Early results of an ongoing phase I study of cisplatin, irinotecan, and radiation in resectable and locally advanced unresectable esophageal cancer is also discussed. Preliminary data on all of these combinations suggest promising activity in upper gastrointestinal malignancies.