Fludarabine combined with radiotherapy in patients with locally advanced NSCLC lung carcinoma: a phase I study

Fludarabine is an adenine nucleoside analogue that has significant activity in hematological malignancies and has shown promising activity in combination with radiation in preclinical solid tumor models. We designed a phase I trial exploring concurrent fludarabine and radiotherapy in patients with advanced non-small cell lung cancer (NSCLC) to determine the maximum tolerated dose (MTD) of fludarabine given with concurrent irradiation. Thirteen patients with stage IIIB NSCLC received thoracic irradiation of 60 Gy. Fludarabine was administered during the 5th and 6th week of radiotherapy. Doses started at 10 mg/m(2) per day and increased by steps of 3 mg/m(2) per day. At a daily dose of 16 mg/m(2), one out of six patients developed a grade 4 leukopenia, and one a grad 3 pneumonitis. Further grade III toxicity was not observed. The dose of 13 mg/m(2) was identified as the MTD. All patients developed a fludarabine dose-dependent lymphocytopenia. Fludarabine can be safely administered concurrently with radiation at a daily dose of 13 mg/m(2) during the final 2 weeks of radiotherapy. Further prospective clinical studies are required to establish the potential role of concurrent fludarabine and radiotherapy in the treatment of locally advanced inoperable NSCLC.