THE COMBINATION OF PACLITAXEL AND CARBOPLATIN AS FIRST-LINE CHEMOTHERAPY IN PATIENTS WITH STAGE-III AND STAGE IV OVARIAN-CANCER - A PHASE I-II STUDY

The combination of paclitaxel 135 mg/m(2) (24-hour infusion) and cispl atin 75 mg/m(2) is now considered the standard treatment in first-line chemotherapy for stage III suboptimally debulked and stage IV ovarian cancer. Interest is focused on the possibility of evaluating the comb ination of paclitaxel with carboplatin, because it was found to be les s nefrotoxic and less neurotoxic than cisplatin. This study seeks to d etermine the maximum tolerated dose and to assess the antitumor activi ty of the combination of a 3-hour paclitaxel infusion followed by carb oplatin. Thirty-three chemotherapy-naive patients with stage III-IV ep ithelial ovarian cancer entered this open, nonrandomized dose-finding study. The first dose level investigated was paclitaxel 125 mg/m(2) an d carboplatin 250 mg/m(2): the dose level progression was performed by alternatively increasing paclitaxel 25 mg/m(2) and carboplatin 50 mg/ m(2). Cycles were repeated every 28 days. At least three patients were treated at each dose level. Overall, 233 and 224 cycles, respectively , are evaluable for nonhematologic and hematologic toxicity. Dose-limi ting toxicities (febrile neutropenia and severe fatigue) were observed in two of six patients at level VIII (paclitaxel 225 mg/m(2) and carb oplatin 400 mg/m(2)) and therefore the previous dose-level (paclitaxel 200 mg/m(2) and carboplatin 400 mg/m(2)) was considered as the maximu m tolerated dose. Neutropenia (grade 3-4 in 63% of cycles), neurotoxic ity (grade 2 in 37.5% and grade 3 in 9% of patients), arthromyalgias ( grade 2 in 53% of patients and grade 3 in 3% of patients), and grade 3 alopecia were the most common toxicities observed. The incidence of t hrombocytopenia was low (grade 3 in 4% of cycles) and no renal toxicit y was observed. An objective remission was documented in 74% of 31 eva luated patients, including eight complete remissions (26%) confirmed b y second-look surgery. The combination of paclitaxel 200 mg/m(2) ii-ho ur infusion followed by carboplatin 400 mg/m2 (30minute infusion) is a safe and active regimen as first-line chemotherapy for advanced ovari an cancer.