PHASE-I STUDY OF DOCETAXEL WITH CONCOMITANT THORACIC RADIATION-THERAPY

Purpose: The taxanes have demonstrated activity as radiation sensitize rs in preclinical studies. This study was designed to determine the ma ximum-tolerated dose (MTD), optimal schedule, and toxicities of doceta xel in combination with concomitant standard chest radiotherapy. Patie nts and Methods: Twenty-nine patients with advanced non-small-cell lun g or esophageal cancer enrolled in this phase I study to evaluate esca lating docetaxel doses at three schedules. Docetaxel was administered as two 21-day cycles at doses of 40, 60, and 75 mg/m(2) per cycle. Doc etaxel administration schedules were as follows: schedule A, once ever y 3 weeks; schedule B, 2 of 3 weeks; or schedule C, weekly Six weeks o f concomitant standard chest radiotherapy in 1.8- to 2.0-Gy daily frac tions was delivered to 60 Gy total. Results: Dose-limiting esophagitis and neutropenia were encountered with schedules A and B at docetaxel doses of 60 mg/m(2) per cycle. The docetaxel MTD for schedules A and B was 40 mg/m(2) per cycle. Dose-limiting esophagitis was also observed with schedule C; however, there was no neutropenia. For schedule C, w e identified the MTD as 60 mg/m(2) per cycle (20 mg/m(2)/wk). Other to xicities encountered included thrombocytopenia, hypersensitivity react ion, and pulmonary infiltrates (fatal in two patients). Late toxicity of esophageal stricture occurred in five patients. Conclusion: Esophag itis and neutropenia are the dose-limiting toxicities of docetaxel adm inistered with concomitant chest radiotherapy. Weekly administration o f docetaxel allows for the highest total docetaxel dose during chest r adiotherapy. We identified the recommended phase II docetaxel dose as 20 mg/m(2) administered weekly with concomitant chest radiotherapy for 6 weeks. (C) 1998 by American Society of Clinical Oncology.