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

Irinotecan (Camptosar) is an active chemotherapeutic agent for lung, gastri c, esophageal, and colorectal cancers and a potent radiosensitizer. This ph ase I study was designed to assess the maximum tolerated dose of weekly iri notecan combined with concurrent radiotherapy for patients with locally adv anced, unresectable gastric, gastroesophageal junction, or esophageal cance r. Patients who received previous chemotherapy (excluding irinotecan) or wh o experienced recurrent cancer after surgery were eligible for this protoco l. 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/ m(2) infused ove r 90 minutes given weekly for 5 weeks. Subsequent nose levels were increase d in 10 mg/m(2) increments to 40, 50, 60, and 70 mg/m(2). Of 15 patients wh o have been enrolled to date, all are evaluable for toxicities and 12 for r esponse. Major hematologic toxicities (grade 3/4) were neutropenia, chills, hemorrhage, and anemia. Grade 3/4 gastrointestinal toxicities included nau sea, vomiting, dehydration, anorexia, and constipation. Other severe nonhem atologic toxicities included fatigue, hypotension, and hypothermia, as well as cardiovascular toxicities. There was no severe dial rhea and no treatme nt-related deaths. Of the 12 evaluable patients, 7 (58%) responded, includi ng 2 complete responses; 4 (30%) had Ito change and 1 had progressive disea se. Survival ranged from 1 month to 15 months, with a median survival of 8 months. When the total dose of irinotecan given concurrently with radiother apy was higher than 250 mg/m(2): patients experienced significantly more se vere grade 3/4 toxicities than with lower doses (P =. 04), with no improvem ent in response rate. It was concluded that weekly doses of irinotecan of u p to 60 mg/m(2) with concurrent radiotherapy given over 5 weeks was feasibl e and demonstrated good response. This regimen did not cause severe diarrhe a or pneumonitis, but neutropenia and fatigue were major toxicities. The st udy continues to accrue.