IRINOTECAN AND CISPLATIN IN UPPER GASTROINTESTINAL MALIGNANCIES

Irinotecan (CPT-11 [Camptosar]), an active agent in the treatment of f uorouracil-refractory colorectal cancer, has antitumor activity in upp er gastrointestinal cancers. Clinical trials from Japan indicate antit umor responses in gastric and pancreatic cancers. Cisplatin (Platinol) , a central agent in the treatment in the treatment of upper gastroint estinal malignancies, is a logical drug to study in combination with i rinotecan in upper gastrointestinal cancers. In vitro studies have sho wn important sequence-dependent synergy of cisplatin/irinotecan combin ation therapy. Irinotecan appears to prevent removal of cisplatin-indu ced DNA-interstrand cross-links. Initial phase I and II trials of cisp latin plus irinotecan appear to confirm this synergy, with Japanese tr ials in gastric cancer showing an encouraging rate of response with ac ceptable toxicity. A phase I trial conducted at Memorial Sloan-Ketteri ng Cancer Center has demonstrated the safety and tolerability of weekl y cisplatin and irinotecan. Currently, a phase II trial of this weekly regimen is under way in patients with metastatic or recurrent esophag eal cancer. The response proportion compares favorably to standard the rapy, and relatively mild toxicity. Other phase II studies, including single-agent irinotecan in esophageal cancer and the combination of ci splatin and irinotecan in gastric cancer, are being initiated at other US institutions.