Medline ® Abstracts for References 21-24
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
J Clin Oncol. 2010;28(20):3323. Epub 2010 May 24.
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.
University Paris Descartes, Assistance Publique-Hôpitaux de Paris, Hôpital Hôtel Dieu, Paris, France. email@example.com
Decreased hypersensitivity reactions with carboplatin-pegylated liposomal doxorubicin compared to carboplatin-paclitaxel combination: analysis from the GCIG CALYPSO relapsing ovarian cancer trial.
Joly F, Ray-Coquard I, Fabbro M, Donoghoe M, Boman K, Sugimoto A, Vaughan M, Reinthaller A, Vergote I, Ferrandina G, Dell'Anna T, Huober J, Pujade-Lauraine E
Gynecol Oncol. 2011;122(2):226. Epub 2011 May 14.
OBJECTIVE: To describe and analyze observed hypersensitivity reactions (HSR) from the randomized, multicenter phase III CALYPSO trial that evaluated the efficacy and safety of the combination of carboplatin and pegylated liposomal doxorubicin (CD) compared with standard carboplatin-paclitaxel (CP) in patients with platinum-sensitive relapsed ovarian cancer (ROC).
METHODS: HSR documented within case report forms and SAE reports were specifically analyzed. Analyses were based on the population with allergy of any grade and for grade>2 allergy.
RESULTS: Overall 976 patients were recruited to this phase III trial, with toxicity data available for 466 and 502 on the CD and CP arms, respectively. There was a 15.5% HSR rate associated with CD (2.4% grade>2) versus 33.1% with CP (8.8% grade>2), p<0.001. HSRs occurred more often during first cycle in the CD (46%) arm than in the CP arm (16%). Multivariate predictors of allergy were chemotherapy regimen and age; patients randomized to CD and patients≥70 years old on CP had less allergy. Few patients (<6%) stopped treatment due to allergy. Allergy rates were higher in patients who did not receive prior supportive treatment; however there was no relationship between allergy and the type of carboplatin product received, or response rate.
CONCLUSIONS: Use of PLD with carboplatin instead of paclitaxel and older age were the only 2 factors predicting a low rate of HSRs in patients with ROC. CD has previously demonstrated superior progression-free survival and therapeutic index than CP. Taken together these data support the use of CD as a safe and effective therapeutic option for platinum-sensitive ROC.
Centre François Baclesse, Medical Oncology Department, Caen, France. firstname.lastname@example.org
Final overall survival results of phase III GCIG CALYPSO trial of pegylated liposomal doxorubicin and carboplatin vs paclitaxel and carboplatin in platinum-sensitive ovarian cancer patients.
Wagner U, Marth C, Largillier R, Kaern J, Brown C, Heywood M, Bonaventura T, Vergote I, Piccirillo MC, Fossati R, Gebski V, Lauraine EP
Br J Cancer. 2012 Aug;107(4):588-91. Epub 2012 Jul 26.
BACKGROUND: The CALYPSO phase III trial compared CD (carboplatin-pegylated liposomal doxorubicin (PLD)) with CP (carboplatin-paclitaxel) in patients with platinum-sensitive recurrent ovarian cancer (ROC). Overall survival (OS) data are now mature.
METHODS: Women with ROC relapsing>6 months after first- or second-line therapy were randomised to CD or CP for six cycles in this international, open-label, non-inferiority trial. The primary endpoint was progression-free survival. The OS analysis is presented here.
RESULTS: A total of 976 patients were randomised (467 to CD and 509 to CP). With a median follow-up of 49 months, no statistically significant difference was observed between arms in OS (hazard ratio = 0.99 (95% confidence interval 0.85, 1.16); log-rank P = 0.94). Median survival times were 30.7 months (CD) and 33.0 months (CP).No statistically significant difference in OS was observed between arms in predetermined subgroups according to age, body mass index, treatment-free interval, measurable disease, number of lines of prior chemotherapy, or performance status. Post-study cross-over was imbalanced between arms, with a greater proportion of patients randomised to CP receiving post-study PLD (68%) than patients randomised to CD receiving post-study paclitaxel (43%; P<0.001).
CONCLUSION: Carboplatin-PLD led to delayed progression and similar OS compared with carboplatin-paclitaxel in platinum-sensitive ROC.
Department of Gynecology, Gynecologic Endocrinology and Oncology, University Hospital of Gießen and Marburg, Baldingerstrasse, 35043 Marburg, Germany. email@example.com
The role of pegylated liposomal doxorubicin in ovarian cancer: a meta-analysis of randomized clinical trials.
Gibson JM, Alzghari S, Ahn C, Trantham H, La-Beck NM
Oncologist. 2013;18(9):1022. Epub 2013 Jul 23.
BACKGROUND: Recent studies suggest that carboplatin with pegylated liposomal doxorubicin (C+PLD) is as efficacious as carboplatin with paclitaxel (C+P) and possibly is more tolerable for ovarian cancer therapy. Pegylated liposomal doxorubicin (PLD) may also be efficacious and tolerable as monotherapy in recurrent or platinum-resistant disease. We performed a meta-analysis of randomized trials in order to elucidate the role of PLD in ovarian cancer.
METHODS: We searched PubMed, Scopus, and ISI Web of Knowledge for studies comparing C+PLD with C+P and comparing PLD with another monotherapy. Summary hazard ratios (HRs) and relative risks with their corresponding 95% confidence intervals (CIs) were calculated using a fixed-effects model.
RESULTS: Three trials were included in the doublet regimen analysis, and five trials were included in the monotherapy regimen analysis. C+PLD provided superior progression-free survival (PFS) (HR, 0.87; 95% CI, 0.78-0.96) and similar overall survival (OS; HR, 0.95; 95% CI, 0.84-1.07) compared with C+P. There was no evidence of improved tolerability: C+PLD had more gastrointestinal toxicity, anemia, thrombocytopenia, cutaneous toxicity, and mucositis/stomatitis, although there was less neutropenia, neuropathy, and alopecia. PLD monotherapy had similar PFS (HR, 0.99; 95% CI, 0.89-1.11) and OS (HR, 0.99; 95% CI, 0.88-1.11) to other monotherapies, but it was more tolerable. There was less neutropenia, anemia, thrombocytopenia, and gastrointestinal toxicity, although cutaneous toxicity was increased.
CONCLUSION: C+PLD had better PFS and similar OS compared with C+P and had a very different toxicity profile. Therapy selection could be based on patient risks for side effects. PLD is as efficacious as other monotherapies and is more tolerable.
Department of Immunotherapeutics and Biotechnology, Texas Tech University Health Sciences Center School of Pharmacy, Abilene, Texas, USA;