Experimental studies have shown that vinorelbine is a powerful radiosensitizer 
in vitro. To date, no reports on clinical activity of the single agent 
vinorelbine as radiosensitizer have been published. The aim of the present phase 
I study was to determine the maximum tolerated dose (MTD) of vinorelbine 
administered daily concurrently with thoracic radiotherapy, with or without 
amifostine support, in the treatment of locally advanced non small cell lung 
cancer. In vitro studies have shown that vinorelbine can potentiate the 
antitumor effects of radiation therapy. Amifostine is a sulphydril compound that 
has shown to protect normal tissues from chemotherapy and radiotherapy-induced 
toxicities. Radiotherapy lasted 6 weeks and the total dose was 55 Gy. The daily 
fraction was 1.8 Gy, administered 5 days a week for 5 weeks and increased to 2.0 
Gy during the sixth and last week. Concurrent vinorelbine was administered daily 
with a planned escalation of the dose from 4, to 5 and 6 mg/m(2). Fourteen 
patients were enrolled in the study. The first dose of vinorelbine was 4 mg/m(2) 
and it showed to be feasible without dose-limiting toxicity (DLT). Instead, the 
second dose level of 5 mg/m(2) was unfeasible because three out of six patients 
had DLT (grade 4 neutropenia, treatment interruption longer than 2 weeks for 
prolonged grade 2 neutropenia and treatment interruption longer than 2 weeks for 
prolonged grade 3 esophagitis together with grade 4 dyspnea). At that time, the 
study continued adding amifostine to vinorelbine in order to increase its MTD. 
Amifostine was administered by means of subcutaneous injection 15 min before 
each radiotherapy fraction at the fixed dose of 300 mg/m(2). However, 5 mg/m(2) 
of vinorelbine were considered unfeasible even with amifostine support because 
three out of five patients showed DLT (grade 4 neutropenia, febrile grade 4 
neutropenia and grade 3 liver toxicity). Among 14 patients enrolled in the 
study, eight completed the planned treatment because six patients experienced 
DLT, which determined treatment interruption. Overall, four partial and two 
complete responses were observed. Two partial and one complete response were 
observed in those three patients who had been treated with the first dose of 
vinorelbine. In conclusion, our data show that the MTD of daily vinorelbine is 4 
mg/m(2). Therefore, this is the recommended dose of daily vinorelbine to be 
administered with concurrent thoracic radiotherapy in a phase II trial. Finally, 
amifostine administered subcutaneously failed to increase the MTD of daily 
vinorelbine.