Phase III Randomized Trial of Docetaxel-Carboplatin Versus Paclitaxel-Carboplatin as First-line Chemotherapy for Ovarian Carcinoma

Abstract

Background: Chemotherapy with a platinum agent and a taxane (paclitaxel) is considered the standard of care for treatment of ovarian carcinoma. We compared the combination of docetaxel–carboplatin with the combination of paclitaxel–carboplatin as first-line chemotherapy for stage Ic–IV epithelial ovarian or primary peritoneal cancer. Methods: We randomly assigned 1077 patients to receive docetaxel at 75 mg/m ² of body surface area (1-hour intravenous infusion) or paclitaxel at 175 mg/m ² (3-hour intravenous infusion). Both treatments then were followed by carboplatin to an area under the plasma concentration–time curve of 5. The treatments were repeated every 3 weeks for six cycles; in responding patients, an additional three cycles of single-agent carboplatin was permitted. Survival curves were calculated by the Kaplan–Meier method, and hazard ratios were estimated with the Cox proportional hazards model. All statistical tests were two-sided. Results: After a median follow-up of 23 months, both groups had similar progression-free survival (medians of 15.0 months for docetaxel–carboplatin and 14.8 months for paclitaxel–carboplatin; hazard ratio [HR] docetaxel–paclitaxel = 0.97, 95% confidence interval [CI] = 0.83 to 1.13; P = .707), overall survival rates at 2 years (64.2% and 68.9%, respectively; HR = 1.13, 95% CI = 0.92 to 1.39; P = .238), and objective tumor (58.7% and 59.5%, respectively; difference between docetaxel and paclitaxel = –0.8%, 95% CI = –8.6% to 7.1%; P = .868) and CA-125 (75.8% and 76.8%, respectively; difference docetaxel–paclitaxel = –1.0%, 95% CI = –7.2% to 5.1%; P = .794) response rates. However, docetaxel–carboplatin was associated with substantially less overall and grade 2 or higher neurotoxicity than paclitaxel–carboplatin (grade ≥2 neurosensory toxicity in 11% versus 30%, difference = 19%, 95% CI = 15% to 24%; P <.001; grade ≥2 neuromotor toxicity in 3% versus 7%, difference = 4%, 95% CI = 1% to 7%; P <.001). Treatment with docetaxel–carboplatin was associated with statistically significantly more grade 3–4 neutropenia (94% versus 84%, difference = 11%, 95% CI = 7% to 14%; P <.001) and neutropenic complications than treatment with paclitaxel–carboplatin, although myelosuppression did not influence dose delivery or patient safety. Global quality of life was similar in both arms, but substantive differences in many symptom scores favored docetaxel. Conclusions: Docetaxel–carboplatin appears to be similar to paclitaxel–carboplatin in terms of progression-free survival and response, although longer follow-up is required for a definitive statement on survival. Thus, docetaxel–carboplatin represents an alternative first-line chemotherapy regimen for patients with newly diagnosed ovarian cancer.