Trabectedin Plus Pegylated Liposomal Doxorubicin in Recurrent Ovarian Cancer

Columbia University, New York, New York, United States
Journal of Clinical Oncology (Impact Factor: 18.43). 07/2010; 28(19):3107-14. DOI: 10.1200/JCO.2009.25.4037
Source: PubMed


The objective of this study was to compare the efficacy and safety of trabectedin plus pegylated liposomal doxorubicin (PLD) with that of PLD alone in women with recurrent ovarian cancer after failure of first-line, platinum-based chemotherapy.
Women > or = 18 years, stratified by performance status (0 to 1 v 2) and platinum sensitivity, were randomly assigned to receive an intravenous infusion of PLD 30 mg/m(2) followed by a 3-hour infusion of trabectedin 1.1 mg/m(2) every 3 weeks or PLD 50 mg/m(2) every 4 weeks. The primary end point was progression-free survival (PFS) by independent radiology assessment.
Patients (N = 672) were randomly assigned to trabectedin/PLD (n = 337) or PLD (n = 335). Median PFS was 7.3 months with trabectedin/PLD v 5.8 months with PLD (hazard ratio, 0.79; 95% CI, 0.65 to 0.96; P = .0190). For platinum-sensitive patients, median PFS was 9.2 months v 7.5 months, respectively (hazard ratio, 0.73; 95% CI, 0.56 to 0.95; P = .0170). Overall response rate (ORR) was 27.6% for trabectedin/PLD v 18.8% for PLD (P = .0080); for platinum-sensitive patients, it was 35.3% v 22.6% (P = .0042), respectively. ORR, PFS, and overall survival among platinum-resistant patients were not statistically different. Neutropenia was more common with trabectedin/PLD. Grade 3 to 4 transaminase elevations were also more common with the combination but were transient and noncumulative. Hand-foot syndrome and mucositis were less frequent with trabectedin/PLD than with PLD alone.
When combined with PLD, trabectedin improves PFS and ORR over PLD alone with acceptable tolerance in the second-line treatment of recurrent ovarian cancer.

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    • "Use of chemoresponse assays during primary therapy may help to identify patients with platinum-resistant disease, potentially allowing for consideration of alternate clinically validated [5] or similarly appropriate [65–67] treatments, as well as prognostic stratification of patients in prospective clinical trials and/or modification of primary therapies “off trial” such as the addition of bevacizumab or other targeted therapies to standard carboplatin/paclitaxel treatment [62–64]. Likewise, in the recurrent disease setting where there is no single standard of care, CRSAs may assist oncologists with prioritization of the various single-agent therapies used with or without platinum therapies [54–56]. "
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    ABSTRACT: The objective of this review is to summarize recent scientific and medical literature regarding chemoresponse assays or chemotherapy sensitivity and resistance assays (CSRAs), specifically as applied to epithelial ovarian cancer. A total of sixty-seven articles, identified through PubMed using the key words "in vitro chemoresponse assay," "chemo sensitivity resistance assay," "ATP," "HDRA," "EDR," "MiCK," and "ChemoFx," were reviewed. Recent publications on marker validation, including relevant clinical trial designs, were also included. Recent CSRA research and clinical studies are outlined in this review. Published findings demonstrate benefits regarding patient outcome with respect to recent CSRAs. Specifically, analytical and clinical validations, as well as clinical utility and economic benefit, of the most common clinically used CSRA in the United States support its use to aid in making effective, individualized clinical treatment selections for patients with ovarian cancer.
    Clinical and Translational Oncology 07/2014; 16(9). DOI:10.1007/s12094-014-1192-8 · 2.08 Impact Factor
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    • "Trabectedin in combination with pegylated liposomal doxorubicin (PLD) has been approved in Europe for treatment of platinum-sensitive recurrent ovarian cancer. In a pivotal Phase III trial (OVA-301), the combination of trabectedin and PLD was found to be more effective than PLD alone for patients with platinum-sensitive recurrent disease, with a higher response rate (35.3 vs. 22.6%) and increased PFS (median PFS 9.2 vs. 7.5 months) (79). "
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    ABSTRACT: The majority of women who are diagnosed with epithelial ovarian cancer present with extensive peritoneal carcinomatosis and are rarely cured by conventional chemotherapy. Ovarian cancer cells typically disseminate by shedding into the peritoneal fluid and implant on the mesothelium-lined peritoneal surfaces that overlie connective and white adipose tissues. Emerging evidence indicates that ovarian tumor progression is orchestrated by dynamic interplay between tumor cells and a variety of stromal cells such as adipocytes, endothelial cells, fibroblasts, mesenchymal stem cells, macrophages, and other immune cells. This mini-review discusses the biological significance of the heterotypic cellular interactions in the ovarian tumor microenvironment and the therapeutic implications of targeting these interactions.
    Frontiers in Oncology 02/2014; 4:18. DOI:10.3389/fonc.2014.00018
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    • "The toxicity related to trabectedin plus PLD was acceptable. Benefits appeared more evident in the PS subset PFS (median PFS: 9.2 months vs. 7.5 months; p = 0.0170) and even more pronounced in patients with PPS disease with a PFI of 6–12 months PFS (median PFS: 7.4 months vs. 5.5 months; p = 0.0015) [19] [27] [68] [69]. It was the first positive randomized phase III trial in ROC that included a non-platinum and non-taxane combination. "
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    ABSTRACT: Ovarian cancer (OC) is the leading cause of death from gynecological malignancies. In spite of high response rates to the standard front-line treatment for advanced disease with cytoreductive surgical debulking, followed by platinum/taxane-based chemotherapy, most patients eventually relapse developing drug-resistant disease. Owing to the molecular heterogeneity, genetic instability and mutagenicity of OC, increases in survival might be achieved by translating recent insights at the morpho-molecular levels to individual therapeutic strategies. Several emerging treatments have been shown to be active in platinum-sensitive (PS) recurrent OC (ROC), but an optimal strategy still has not been established. Based on the recent results, it is likely that the introduction of novel non-platinum based chemotherapies and molecular targeted therapies will have a major impact on the management of ROC. Some current strategies are focused on the extension of platinum-free interval (PFI) in patients with PS, particularly in those with partially PS disease. Apparently, the PFI extension by an effective non-platinum intervention, such as trabectedin plus pegylated liposomal doxorubicin (PLD), may reduce cumulative platinum-induced toxicities leading to longer survival after the reintroduction of subsequent platinum. The introduction of novel therapies, such as the antiangiogenic monoclonal antibody bevacizumab, opens a new field of targeted therapies in this indication. In this review, we aim to outline the therapeutic potential of new emerging approaches, particularly the role of non-platinum therapy with trabectedin in combination with PLD in patients with PS ROC.
    Cancer Treatment Reviews 08/2013; 40(3). DOI:10.1016/j.ctrv.2013.08.001 · 7.59 Impact Factor
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