Pegylated liposomal Doxorubicin and Carboplatin compared with Paclitaxel and Carboplatin for patients with platinum-sensitive ovarian cancer in late relapse.
OBJECTIVE
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).


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.


CONCLUSIONS
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.
Pujade-Lauraine
Eric
E
University Paris Descartes, Assistance Publique-Hôpitaux de Paris, Hôpital Hôtel Dieu, Paris, France. epujade@arcagy.org
Wagner
Uwe
U
Aavall-Lundqvist
Elisabeth
E
Gebski
Val
V
Heywood
Mark
M
Vasey
Paul A
PA
Volgger
Birgit
B
Vergote
Ignace
I
Pignata
Sandro
S
Ferrero
Annamaria
A
Sehouli
Jalid
J
Lortholary
Alain
A
Kristensen
Gunnar
G
Jackisch
Christian
C
Joly
Florence
F
Brown
Chris
C
Le Fur
Nathalie
N
du Bois
Andreas
A
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage*; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology; D017239:Paclitaxel / Q000008:administration & dosage*; D010984:Platinum / Q000627:therapeutic use; D011092:Polyethylene Glycols / Q000008:administration & dosage*; D012008:Recurrence
C506643:liposomal doxorubicin; D011092:Polyethylene Glycols; D010984:Platinum; D004317:Doxorubicin; D016190:Carboplatin; D017239:Paclitaxel