Phase II study of carboplatin followed by sequential gemcitabine and paclitaxel as first-line treatment for advanced ovarian cancer

Abstract

The aim of this exploratory phase II study was to evaluate sequential chemotherapy with carboplatin followed by gemcitabine-paclitaxel combination in chemonaive patients with advanced ovarian cancer. The primary objective was to evaluate time to progressive disease (TTPD); secondary objectives included the evaluation of 1- and 3-year survival, response rates, and toxicity. Following initial debulking surgery or biopsy, patients with FIGO stage IIC-IV disease received four cycles of carboplatin area under the curve (AUC) 6 (day 1) every 21 days, followed by four cycles of gemcitabine 1000 mg/m(2) (days 1 and 8) and paclitaxel 175 mg/m(2) (day 8) every 21 days. A total of 47 patients enrolled, 44 (93.6%) completed the initial four cycles, and 39 patients (82.9%) completed the planned eight cycles. The median and maximum lengths of follow-up were 31.2 and 43.7 months, respectively. Median TTPD was 13.8 months (95% CI, 11.6-21.0 months), and median survival time was 31.2 months (95% CI, 25.2-39.6 months). Survival at 1 and 3 years was 95.7% and 44.2%, respectively. Of the 43 evaluable patients, most (95.3%) of them achieved a CA-125 marker response based on Gynecologic Cancer Intergroup (GCIG) definition. The partial response rate in the seven patients with measurable disease was 46.4%. Myelosuppression was the major toxicity, with grade 3 and 4 neutropenia observed in 76.6% patients and thrombocytopenia in 12.8% patients. The sequential approach of carboplatin followed by gemcitabine-paclitaxel as first-line treatment for patients with ovarian cancer is feasible and well tolerated, and depending upon the findings from other major trials, it may merit further evaluation.

Mixed Liposome Approach for Ratiometric and Sequential Delivery of Paclitaxel and Gemcitabine

“…Combination therapy can achieve high therapeutic efficacy, reduce the dose requirement, and attenuate the development of drug resistance by targeting multiple biological mechanisms (2, 3). For example, paclitaxel (PTX) and gemcitabine (GEM) are used in combination for the treatment of ovarian cancer (4, 5), pancreatic cancer (6, 7), breast cancer (8, 9), and biliary cancer (10). PTX stabilizes microtubules, prevents the formation of normal mitotic apparatus, thereby blocking cancer cells at the G 2 /M phase (11).…”

Effects of sequential paclitaxel–carboplatin followed by gemcitabine-based chemotherapy compared with paclitaxel-carboplatin therapy administered to patients with advanced epithelial ovarian cancer

“…Diverse randomized trials are investigating sequential chemotherapy as first-line treatment for ovarian cancer to further improve patients’ outcomes; [20,39–43] however, the results are inconsistent. For example, Steer et al [42] enrolled 20 patients with epithelial ovarian cancer (FIGO III–IV) and administered a sequential double regimen comprising gemcitabine and oxaliplatin before 4 cycles of carboplatin and paclitaxel that achieved an 85% overall response rate, but with unacceptable neurotoxicity.…”

“…For example, Steer et al [42] enrolled 20 patients with epithelial ovarian cancer (FIGO III–IV) and administered a sequential double regimen comprising gemcitabine and oxaliplatin before 4 cycles of carboplatin and paclitaxel that achieved an 85% overall response rate, but with unacceptable neurotoxicity. Friedlander [20] et al treated 47 patients (previously untreated) with advanced ovarian cancer with sequential carboplatin followed by combined gemcitabine–paclitaxel. In this study, myelosuppression was the predominant toxicity, the frequencies of grades –3 and –4 neutropenic toxicities and thrombocytopoenia were 76.6% and 12.8%, respectively.…”

“…[18,19] Moreover, gemcitabine shows promising results with low toxicity when incorporated in triple-drug regimens or as a sequential agent. [20–22] …”

Proteogenomic Studies in Epithelial Ovarian Cancer: Established Knowledge and Future Needs

“…Despite the genetic distinction between the various ovarian cancer histological subtypes [18], they are commonly treated in the same manner: namely, with maximal cytoreductive surgery [19][20][21][22] followed by platinum-and taxane-based chemotherapy [4,23,24]. It would be valuable if we could use molecular expression profiles to classify ovarian tumors into distinct subtypes based on the biological behavior and to better predict individual patient outcomes based on a such a personal molecular 'biosignature' [25,26].…”