• David H Ilson.
• Gastrointestinal Oncology Division, Solid Tumor Service Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
• Oncology Ny. 2004 Dec 1; 18 (14 Suppl 14): 22-5.

AbstractEsophageal cancer is a rare but highly virulent malignancy in the United States, and adenocarcinoma of the esophagus has had the most rapid rate of increase of any solid tumor malignancy. Systemic metastatic disease is present in 50% of patients at diagnosis. In the remaining 50% presenting with local regional disease, systemic metastatic disease will develop in the vast majority of these patients. The limited efficacy and toxicity of conventional fluorouracil (5-FU)/cisplatin-based chemotherapy has prompted the evaluation of newer agents. Irinotecan (Camptosar) has shown promising single-agent activity in a number of gastrointestinal cancers, including colorectal, pancreatic, and esophagogastric cancer. The phase II evaluation of the combination of weekly irinotecan and cisplatin has shown encouraging response rates exceeding 30% to 50% in esophageal and gastric cancer. Hematologic toxicity using a schedule of 4 consecutive weeks of therapy followed by 2 weeks of rest prompted interest in a multicenter trial evaluation of a change in therapy delivery to 2 weeks on and 1 week off. Cisplatin at 30 mg/m2 was administered with irinotecan at 65 mg/m2, days 1 and 8, on an every-21-day schedule. Thirty-nine patients were entered on study, with 36 evaluable for toxicity and 31 evaluable for response. Grade 3/4 neutropenia was observed in only 22% of patients, reduced from 49% in a prior phase II trial employing 4 consecutive weeks of therapy. Confirmed major responses were observed in 36% of patients (10 of 28). A change to a day 1, day 8 schedule of weekly irinotecan and cisplatin appears to reduce hematologic toxicity but maintain antitumor activity in patients with esophageal and gastroesophageal junction cancer. A randomized phase II trial in gastric and esophageal cancer comparing weekly irinotecan and cisplatin to epirubicin, cisplatin, and 5-FU, and to infusional 5-FU in combination with irinotecan, will be conducted by the Cancer and Leukemia Group B (CALGB). A phase II trial combining this schedule of weekly cisplatin and irinotecan and concurrent radiotherapy given as preoperative therapy will also be conducted by the CALGB as a pilot trial.

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