Gemcitabine concurrent with thoracic radiotherapy after induction chemotherapy with gemcitabine/vinorelbine in locally advanced non-small cell lung cancer: a phase I study.

PURPOSE: To determine the maximum tolerated dose (MTD) of gemcitabine every 2 weeks to a concurrent radiotherapy administered during an aggressive program of sequential and simultaneous radio-/chemotherapy for locally advanced, unresectable non-small cell lung cancer (NSCLC).

PATIENTS AND METHODS: Ten patients with histologically confirmed NSCLC were observed and treated in accordance with a combined radio-/chemotherapy protocol. This included two cycles of induction chemotherapy with gemcitabine (1,200 mg/m(2)) and vinorelbine (30 mg/m(2)) at days 1, 8 and 22, 29, followed by concurrent radiotherapy including [(18)F] fluorodeoxyglucose positron emission tomography-(FDG-PET-)based target volume definition (2.0 Gy/d; total dose 66.0 Gy) and chemotherapy with gemcitabine every 2 weeks at days 43, 57, and 71. The initial dose was 300 mg/m(2). The dose of gemcitabine was increased by 100 mg/m(2) until the MTD was realized. Three patients were enrolled for each dose level.

RESULTS: Dose-limiting toxicity (DLT) was identified for the patient group receiving gemcitabine 500 mg/m(2), due to grade 2 esophagitis (next to grade 3) in all patients. 6 weeks after the completion of radio-/chemotherapy, most patients still presented treatment-induced esophagitis. In accordance with expected complications, such as esophagitis, dysphagia and odynophagia, the MTD was defined at this dose level, although no DLT grade 3 was reached.

CONCLUSION: After induction chemotherapy, the MTD and frequency of gemcitabine in locally advanced NSCLC is 500 mg/m(2) every 2 weeks during a maximum of 7 weeks of thoracic radiotherapy.