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

• Published in: Journal of clinical oncology Vol. 28; no. 20; pp. 3323 - 3329
• Main Authors: PUJADE-LAURAINE, Eric, WAGNER, Uwe, SEHOULI, Jalid, LORTHOLARY, Alain, KRISTENSEN, Gunnar, JACKISCH, Christian, JOLY, Florence, BROWN, Chris, LE FUR, Nathalie, DU BOIS, Andreas, AAVALL-LUNDQVIST, Elisabeth, GEBSKI, Val, HEYWOOD, Mark, VASEY, Paul A, VOLGGER, Birgit, VERGOTE, Ignace, PIGNATA, Sandro, FERRERO, Annamaria
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Society of Clinical Oncology 10.07.2010
• Subjects: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological and medical sciences; Carboplatin - administration & dosage; Disease-Free Survival; Doxorubicin - administration & dosage; Doxorubicin - analogs & derivatives; Drug Administration Schedule; Female; Female genital diseases; Gynecology. Andrology. Obstetrics; Humans; Medical sciences; Medicin och hälsovetenskap; Middle Aged; Ovarian Neoplasms - drug therapy; Ovarian Neoplasms - pathology; Paclitaxel - administration & dosage; Platinum - therapeutic use; Polyethylene Glycols - administration & dosage; Recurrence; Tumors; Antineoplastic agent; Relapse; Ovary cancer; Doxorubicin; Isomerases; Cancerology; Taxane derivatives; Paclitaxel; Pegylated form; Antimitotic; Platinum II Complexes; Human; DNA topoisomerase (ATP-hydrolysing); Late; Enzyme; Enzyme inhibitor; Liposome; Topoisomerase II inhibitor; Malignant tumor; Female genital diseases; Ovarian diseases; Carboplatin; Anthracyclins; Comparative study; Cancer
• ISSN: 0732-183X; 1527-7755; 1527-7755
• DOI: 10.1200/JCO.2009.25.7519

This 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 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/m(2)) every 4 weeks or CP (carboplatin AUC 5 plus paclitaxel 175 mg/m(2)) 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. Overall 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. To 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.