Phase II dose escalation: A novel approach to balancing efficacy and toxicity of anticancer agents

Background: Small patient numbers in phase I trials may result in a safe bu t ineffective close being recommended for phase II trials. A phrase II dose escalation study may identify a dose that is both safe and effective. The Japanese phase I recommended dose of 60 mg/m(2) of docetaxel (Taxotere(R)) had been ineffective in phase II trials in ovarian carcinoma. patients and methods: Patients previously? treated with one platinum-based regimen for o varian cancer received docetaxel (Taxotere(R)) every 3 weeks. The first dos e tested was 70 mg/m(2). If none of the first 5 evaluable patients responde d, the dose was increased. If at least one patient responded, 10 more patie nts were enrolled. Also, if fewer than 3 of these first 15 evaluable patien ts responded, the dose was increased. If at least 3 patients responded, ano ther 15 patients were scheduled to be enrolled to confirm efficacy. Unaccep table toxicity in 4 of 5 or 10 of 15 patients would stop escalation. Result s: Dose escalation from 70 mg/m(2) was not required because responses were noted with acceptable toxicity levels. Overall response in 25 evaluable pat ients treated at 70 mg/m(2) was 24.0% (95% CI = 9.4-45.1%). 2 Conclusion: D ocetaxel 70 mg/m(2) without premedication was identified as a safe and effe ctive dose. Further testing of the phase II nose escalation design is worth while.