Pegylated Liposomal Doxorubicin and Carboplatin Compared With Paclitaxel and Carboplatin for Patients With Platinum-Sensitive Ovarian Cancer in Late Relapse

Abstract

PurposeThis randomized, multicenter, phase III noninferiority trial was designed to test the efficacy and safety of the combination of pegylated liposomal doxorubicin (PLD) with carboplatin (CD) compared with standard carboplatin and paclitaxel (CP) in patients with platinum-sensitive relapsed/recurrent ovarian cancer (ROC).Patients and MethodsPatients with histologically proven ovarian cancer with recurrence more than 6 months after first- or second-line platinum and taxane-based therapies were randomly assigned by stratified blocks to CD (carboplatin area under the curve [AUC] 5 plus PLD 30 mg/m2) every 4 weeks or CP (carboplatin AUC 5 plus paclitaxel 175 mg/m2) every 3 weeks for at least 6 cycles. Primary end point was progression-free survival (PFS); secondary end points were toxicity, quality of life, and overall survival.ResultsOverall 976 patients were recruited. With median follow-up of 22 months, PFS for the CD arm was statistically superior to the CP arm (hazard ratio, 0.821; 95% CI, 0.72 to 0.94; P = .005); median PFS was 11.3 versus 9.4 months, respectively. Although overall survival data are immature for final analysis, we report here a total of 334 deaths. Overall severe nonhematologic toxicity (36.8% v 28.4%; P < .01) leading to early discontinuation (15% v 6%; P < .001) occurred more frequently in the CP arm. More frequent grade 2 or greater alopecia (83.6% v 7%), hypersensitivity reactions (18.8% v 5.6%), and sensory neuropathy (26.9% v 4.9%) were observed in the CP arm; more hand-foot syndrome (grade 2 to 3, 12.0% v 2.2%), nausea (35.2% v 24.2%), and mucositis (grade 2-3, 13.9% v 7%) in the CD arm.ConclusionTo our knowledge, this trial is the largest in recurrent ovarian cancer and has demonstrated superiority in PFS and better therapeutic index of CD over standard CP.

Doublet Chemotherapy in the Elderly Patient With Ovarian Cancer

“…Numbers of cycles received and dose intensity were identical between older and younger patients. Progression-free survival was statistically superior in the pegylated liposomal doxorubicin arm, at 11.3 months versus 9.4 months [82]. Sixteen percent of patients were older than 70 years of age, and this group completed more than six cycles of planned treatment at the same rate as younger patients with no significant differences in rates of hematologic toxicities.…”

Tolerability, Efficacy, and Safety of Pegylated Liposomal Doxorubicin in Combination with Carboplatin Versus Gemcitabine–Carboplatin for the Treatment of Platinum-Sensitive Recurrent Ovarian Cancer: A Systematic Review

“…The CALYPSO study, an open-label, international, multicenter, randomized phase III trial, evaluated the efficacy and safety of PLD (30 mg/m 2 on day 1) and carboplatin (AUC of 5 on day 1) with those of paclitaxel-carboplatin in patients with epithelial ovarian cancer in late relapse (Ͼ6 months) [25]. The CALYPSO trial enrolled a total of 466 patients in the PLD-carboplatin arm.…”

The causes, diagnosis, and treatment of recurrent ovarian cancer. A literature review and analysis of the authors’ data

“…Совокупность ряда причин является предпосылкой к тому, что рецидивный рак яичников встречается у 50% больных и характеризуется возвратом заболевания после достижения полной ремиссии и при ее сохранении дли-тельное время [4,5].…”