Phase I trial of paclitaxel and etoposide for recurrent ovarian carcinoma - A gynecologic oncology group study

A phase I study was performed to determine the maximum tolerated doses of i ntravenous etoposide and paclitaxel for women with previously treated persi stent or recurrent ovarian cancer. Starting doses were paclitaxel 135 mg/m( 2) during 24 hours and etoposide 50 mg/m(2)/day for 3 consecutive days. The study was designed to escalate first the dose of etoposide, and then the d ose of paclitaxel, in successive cohorts of patients. In an attempt to dete rmine whether toxicity was affected by sequence of the drugs, the order of administration of the two drugs was reversed on alternate cycles. The start ing doses of paclitaxel (135 mg/m(2)/24 hours) and etoposide (50 mg/m(2)/da y x 3) caused severe neutropenia even with the addition of granulocyte colo ny-stimulating factor, and the trial was amended to administer the paclitax el during 3 hours. However, this also proved too myelosuppressive without g rowth factor support. Twenty-one women were treated. A complete response wa s observed in one of nine patients with measurable disease, and a major dec rease in CA-125 was noted in two patients who did not have measurable disea se. Because of the severe myelosuppression observed in most patients, dose reduction was often required after the first cycle. The power to detect seq uence-dependent variation in toxicity was minimal; however, no large differ ences were observed. A combination of the usual doses of these drugs will b e difficult to administer in patients who have received previous chemothera py for ovarian cancer.