Phase I/II study of weekly paclitaxel plus carboplatin and gemcitabine as first-line treatment of advanced-stage ovarian cancer: Pathologic complete response and longitudinal assessment of impact on cognitive functioning

Background.To determine the pathologic complete response rate of advanced ovarian cancer to weekly paclitaxel plus gemcitabine and carboplatin with filgrastim, and assess the longitudinal impact of this regimen on quality-of-life and cognitive functioning.Methods.Fourteen patients with advanced ovarian, peritoneal, or fallopian tube cancer were treated in the phase I portion of the study. Initial doses were paclitaxel: 60 mg/m2 days 1, 8, and 15; gemcitabine: 800 mg/m2 days 1 and 8; and carboplatin: area under the curve (AUC) 5 day 1, every 21 days for 6 cycles with filgrastim. Twenty-seven patients were treated at the phase II dose. Pathologic response was assessed by second-look laparoscopy in patients with complete response. Patients completed longitudinal assessments of quality-of-life and cognitive functioning.Results.Maximally tolerated doses were paclitaxel: 80 mg/m2 days 1 and 8; gemcitabine: 800 mg/m2 days 1 and 8; and carboplatin: AUC 5 day 1, every 21 days. Forty-eight percent of patients (13/27) experienced at least 1 grade 3 nonhematologic toxicity. Fifty percent (95% confidence interval [CI], 31–69%) of assessable patients achieved pathologic complete response. Median progression-free survival was 27.3 months (95% CI, 17.7 months to not reached), and overall survival 43.6 months (95% CI, 42 months to not reached). Cognitive functioning did not decline during or after chemotherapy. More highly educated women reported a perceived decline in concentration and memory while on chemotherapy. Quality-of-life scores were maintained during therapy.Conclusions.Fifty percent of patients with advanced-stage ovarian cancer achieved pathologic complete response to weekly paclitaxel plus gemcitabine and carboplatin. Cognitive functioning did not decline by objective measures, although highly educated women reported subjective impairment.