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

被引:415
作者
Pujade-Lauraine, Eric [1 ]
Wagner, Uwe
Aavall-Lundqvist, Elisabeth
Gebski, Val
Heywood, Mark
Vasey, Paul A.
Volgger, Birgit
Vergote, Ignace
Pignata, Sandro
Ferrero, Annamaria
Sehouli, Jalid
Lortholary, Alain
Kristensen, Gunnar
Jackisch, Christian
Joly, Florence
Brown, Chris
Le Fur, Nathalie
du Bois, Andreas
机构
[1] Univ Paris 05, Hop Hotel Dieu, AP HP, F-75004 Paris, France
关键词
PHASE-III TRIAL; RECURRENT EPITHELIAL OVARIAN; SOUTHWEST-ONCOLOGY-GROUP; RANDOMIZED-TRIAL; SURVIVAL ADVANTAGE; 1ST-LINE TREATMENT; PLUS CARBOPLATIN; INTERGROUP TRIAL; CLINICAL-TRIAL; STAGE-III;
D O I
10.1200/JCO.2009.25.7519
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
引用
收藏
页码:3323 / 3329
页数:7
相关论文
共 39 条
[1]   Randomized trial of pegylated liposomal doxorubicin (PLD) plus carboplatin versus carboplatin in platinum-sensitive (PS) patients with recurrent epithelial ovarian or peritoneal carcinoma after failure of initial platinum-based chemotherapy (Southwest Oncology Group Protocol S0200) [J].
Alberts, David S. ;
Liu, P. Y. ;
Wilczynski, Sharon P. ;
Clouser, Mary C. ;
Lopez, Ana Maria ;
Michelin, David P. ;
Lanzotti, Victor J. ;
Markman, Maurie .
GYNECOLOGIC ONCOLOGY, 2008, 108 (01) :90-94
[2]   IMPROVED THERAPEUTIC INDEX OF CARBOPLATIN PLUS CYCLOPHOSPHAMIDE VERSUS CISPLATIN PLUS CYCLOPHOSPHAMIDE - FINAL REPORT BY THE SOUTHWEST-ONCOLOGY-GROUP OF A PHASE-III RANDOMIZED TRIAL IN STAGE-III AND STAGE-IV OVARIAN-CANCER [J].
ALBERTS, DS ;
GREEN, S ;
HANNIGAN, EV ;
OTOOLE, R ;
STOCKNOVACK, D ;
ANDERSON, P ;
SURWIT, EA ;
MALVLYA, VK ;
NAHHAS, WA ;
JOLLES, CJ .
JOURNAL OF CLINICAL ONCOLOGY, 1992, 10 (05) :706-717
[3]  
[Anonymous], PRINCIPLES PRACTICE
[4]   Clinical trial endpoints in ovarian cancer: Report of an FDA/ASCO/AACR public workshop [J].
Bast, Robert C. ;
Thigpen, J. Tate ;
Arbuck, Susan G. ;
Basen-Engquist, Karen ;
Burke, Laurie B. ;
Freedman, Ralph ;
Horning, Sandra J. ;
Ozols, Robert ;
Rustin, Gordon J. ;
Spriggs, David ;
Wenzel, Lari B. ;
Pazdur, Richard .
GYNECOLOGIC ONCOLOGY, 2007, 107 (02) :173-176
[5]   Advanced epithelial ovarian cancer:: 1998 consensus statements [J].
Berek, JS ;
Bertelsen, K ;
du Bois, A ;
Brady, MF ;
Carmichael, J ;
Eisenhauer, EA ;
Gore, M ;
Grenman, S ;
Hamilton, TC ;
Hansen, SW ;
Harper, PG ;
Horvath, G ;
Kaye, SB ;
Lück, HJ ;
Lund, B ;
McGuire, WP ;
Neijt, JP ;
Ozols, RF ;
Parmar, MKB ;
Piccart-Gebhart, MJ ;
van Rijswijk, R ;
Rosenberg, P ;
Rustin, GJS ;
Sessa, C ;
Thigpen, JT ;
Tropé, C ;
Tuxen, MK ;
Vergote, I ;
Vermorken, JB ;
Willemse, PHB .
ANNALS OF ONCOLOGY, 1999, 10 :87-92
[6]   A PROSPECTIVE RANDOMIZED COMPARISON OF 6 AND 12 CYCLES OF CYCLOPHOSPHAMIDE, ADRIAMYCIN, AND CISPLATIN IN ADVANCED EPITHELIAL OVARIAN-CANCER - A DANISH OVARIAN STUDY-GROUP TRIAL (DACOVA) [J].
BERTELSEN, K ;
JAKOBSEN, A ;
STROYER, I ;
NIELSEN, K ;
SANDBERG, E ;
ANDERSEN, JE ;
AHRONS, S ;
NYLAND, M ;
PEDERSEN, PH ;
LARSEN, G ;
RASMUSSEN, P ;
KIAER, H ;
BICHEL, P ;
JACOBSEN, M ;
HOLUND, B .
GYNECOLOGIC ONCOLOGY, 1993, 49 (01) :30-36
[7]   Epidoxorubicin versus no treatment as consolidation therapy in advanced ovarian cancer: results from a phase II study [J].
Bolis, G ;
Danese, S ;
Tateo, S ;
Rabaiotti, E ;
D'Agostino, G ;
Merisio, C ;
Scarfone, G ;
Polverino, G ;
Parazzini, F .
INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER, 2006, 16 :74-78
[8]   CARBOPLATIN DOSAGE - PROSPECTIVE EVALUATION OF A SIMPLE FORMULA BASED ON RENAL-FUNCTION [J].
CALVERT, AH ;
NEWELL, DR ;
GUMBRELL, LA ;
OREILLY, S ;
BURNELL, M ;
BOXALL, FE ;
SIDDIK, ZH ;
JUDSON, IR ;
GORE, ME ;
WILTSHAW, E .
JOURNAL OF CLINICAL ONCOLOGY, 1989, 7 (11) :1748-1756
[9]   PREDICTION OF CREATININE CLEARANCE FROM SERUM CREATININE [J].
COCKCROFT, DW ;
GAULT, MH .
NEPHRON, 1976, 16 (01) :31-41
[10]   Topotecan compared with no therapy after response to surgery and carboplatin/paclitaxel in patients with ovarian cancer: Multicenter Italian trials in ovarian cancer (MITO-1) randomized study [J].
De Placido, S ;
Scambia, G ;
Di Vagno, G ;
Naglieri, E ;
Lombardi, AV ;
Biamonte, R ;
Marinaccio, M ;
Carteni, G ;
Manzione, L ;
Febbraro, A ;
de Matteis, A ;
Gasparini, G ;
Valerio, MR ;
Danese, S ;
Perrone, F ;
Lauria, R ;
De Laurentiis, M ;
Greggi, S ;
Gallo, C ;
Pignata, S .
JOURNAL OF CLINICAL ONCOLOGY, 2004, 22 (13) :2635-2642