Phase I trial of taxol as a radiation sensitizer with cisplatin in advanced cervical cancer

Objective. The aim of this study was to determine tolerable doses and potential toxicities of taxol, administered weekly, with concomitant cisplatin and radiation therapy in advanced cervical cancer. Methods. Patients with cervical cancer, either with evidence of distant metastatic disease at presentation or otherwise at high risk for recurrent disease, were eligible for this phase I study. Taxol was administered weekly as a 3-hr intravenous infusion in addition to the prescribed radiation therapy. The starting dose was 10 mg/m(2)/week and escalated at 10 mg/m(2)/week increments if tolerated by successive cohorts of three new patients. Cisplatin was given every 3 weeks at 50 mg/m(2). Chemotherapy was continued until radiation was completed. For each patient quality of life was assessed weekly during therapy. Results. Sixteen patients, undergoing a total of 102 cycles, have been enrolled. Dose escalation of taxol from 10 mg/m(2)/week to 50 mg/m(2)/week was well tolerated, with no significant change in quality of life during therapy. Two radiation fractions (0.5%) were delayed due to toxicity from this chemotherapy regimen. Of 102 cycles, 6 resulted in grade 2 and 1 in grade 3 neutropenia, and no patient developed > grade 2 anemia or thrombocytopenia. Three patients developed GI-related toxicities and 1 patient presented with urosepsis during treatment. There was a 93% response rate to this regimen, with 10 patients (63%) presently having no evidence of disease. Conclusions. This study has demonstrated that up to 50 mg/m(2)/week of taxol is well tolerated in patients undergoing radiation therapy for advanced cervical cancer. A phase II trial will assist in determining the efficacy of taxol as a radiation sensitizer in these patients. (C) 1997 Academic Press.