CARBOPALTIN PLUS CAELYX FOR PLATINUM SENSITIVE OVARIAN CANCER

J Clin Oncol. 2010 May 24. [Epub ahead of print]
Pegylated Liposomal Doxorubicin and Carboplatin Compared With Paclitaxel and Carboplatin for Patients With Platinum-Sensitive Ovarian Cancer in Late Relapse.
Pujade-Lauraine E, Wagner U, Aavall-Lundqvist E, Gebski V, Heywood M, Vasey PA, Volgger B, Vergote I, Pignata S, Ferrero A, Sehouli J, Lortholary A, Kristensen G, Jackisch C, Joly F, Brown C, Le Fur N, du Bois A.

University Paris Descartes, Assistance Publique-Hôpitaux de Paris, Hôpital Hôtel-Dieu; Association de Recherche sur les Cancers dont Gynécologiques Groupe d'Investigateurs Nationaux pour l'Etude des Cancers Ovariens, Paris; Centre Catherine De Sienne, Nantes; Centre Hospitalier Universitaire-Centre François Baclesse, Caen, France; Philipps University Marburg, Marburg; University Hospital Charité/Campus Virchow-Klinikum, Berlin; Klinikum Offenbach, Offenbach; Dr Horst Schmidt Klinik, Wiesbaden, Germany; Karolinska University Hospital and Karolinska Institutet Stockholm, Sweden; NHMRC Clinical Trials Centre, Sydney, New South Wales; University of Queensland, Brisbane, Queensland, Australia; British Columbia Cancer Agency, Vancouver, British Columbia, Canada; Medical University Innsbruck, Innsbruck, Austria; University Hospital Leuven, Leuven, Belgium; National Cancer Institute, Naples; Academic Division of Gynecological Oncology, Institute for Cancer Research and Treatment of Candiolo & Azienda Ospedaliera Ordine Mauriziano, Turin, Italy; and Norwegian Radium Hospital, Oslo, Norway.
Abstract

PURPOSE 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 AND METHODS 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. Results 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. CONCLUSION 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.