Phase I study of irinotecan and concurrent radiation therapy for upper GI tumors.

Irinotecan (Camptosar) is an active chemotherapeutic agent for lung, gastric, esophageal, and colorectal cancers and a potent radiosensitizer. This phase I study was designed to assess the maximum tolerated dose of weekly irinotecan combined with concurrent radiotherapy for patients with locally advanced, unresectable gastric, gastroesophageal junction, or esophageal cancer. Patients who received previous chemotherapy (excluding irinotecan) or who experienced recurrent cancer after surgery were eligible for this protocol. The total dose of radiation did not exceed 50.4 Gy (28 fractions of 1.8 Gy each). The starting dose level of irinotecan was 30 mg/m2 infused over 90 minutes given weekly for 5 weeks. Subsequent dose levels were increased in 10 mg/m2 increments to 40, 50, 60, and 70 mg/m2. Of 15 patients who have been enrolled to date, all are evaluable for toxicities and 12 for response. Major hematologic toxicities (grade 3/4) were neutropenia, chills, hemorrhage, and anemia. Grade 3/4 gastrointestinal toxicities included nausea, vomiting, dehydration, anorexia, and constipation. Other severe nonhematologic toxicities included fatigue, hypotension, and hypothermia, as well as cardiovascular toxicities. There was no severe diarrhea and no treatment-related deaths. Of the 12 evaluable patients, 7 (58%) responded, including 2 complete responses; 4 (30%) had no change and 1 had progressive disease. Survival ranged from 1 month to 15 months, with a median survival of 8 months. When the total dose of irinotecan given concurrently with radiotherapy was higher than 250 mg/m2, patients experienced significantly more severe grade 3/4 toxicities than with lower doses (P = .04), with no improvement in response rate. It was concluded that weekly doses of irinotecan of up to 60 mg/m2 with concurrent radiotherapy given over 5 weeks was feasible and demonstrated good response. This regimen did not cause severe diarrhea or pneumonitis, but neutropenia and fatigue were major toxicities. The study continues to accrue.