An Open-Label Phase 2 Study of Twice-Weekly Bortezomib and Intermittent Pegylated Liposomal Doxorubicin in Patients With Ovarian Cancer Failing Platinum-Containing Regimens. Issue 5 (1st June 2012)

• Record Type: Journal Article
• Authors: Parma, Gabriella; Mancari, Rosanna; Del Conte, Gianluca; Scambia, Giovanni; Gadducci, Angiolo; Hess, Dagmar; Katsaros, Dionyssios; Sessa, Cristiana; Rinaldi, Andrea; Bertoni, Francesco; Vitali, Andrea; Catapano, Carlo Vittorio; Marsoni, Silvia; van de Velde, Helgi; Colombo, Nicoletta
• Is Part Of: International journal of gynecological cancer. Volume 22:Issue 5(2012)
• Page Start: 792
• Page End: 800
• Publication Date: 2012-06-01
• Subjects: Bortezomib -- Pegylated liposomal doxorubicin -- Ovarian cancer -- Proteasome inhibitor; Generative organs, Female -- Cancer -- Periodicals; 616.99465
• DOI: 10.1097/IGC.0b013e318251051a
• Languages: English
• ISSNs: 1048-891X

Abstract

Abstract : Background: Pegylated liposomal doxorubicin (PLD) is an established treatment for relapsed ovarian cancer. Preclinical and clinical evidences in other tumor types suggest that the proteasome inhibitor bortezomib can act synergistically with PLD. Methods: Patients with relapsed ovarian cancer (N = 58), previously treated with platinum (100%) and taxane (95%), received bortezomib, 1.3 mg/m 2 intravenous (days 1, 4, 8, and 11), and PLD, 30 mg/m 2 intravenous (day 1), every 3 weeks. Tumor responses were assessed using Response Evaluation Criteria In Solid Tumors and Gynecologic Cancer Intergroup criteria. An optimal 2-stage design was implemented. Gene expression profiling in peripheral blood was characterized before and during treatment in 10 platinum-sensitive patients enrolled in stage 2 of the study. Results: Median number of bortezomib-PLD cycles was 3.5. Of 38 patients in the platinum-sensitive group, 9 responses were observed (median duration, 4.8 months). The platinum-resistant group was closed at stage 1 owing to lack of response. Toxicity was moderate and mainly consisted of hematologic, gastrointestinal, and mucositis events. Of the total 58 patients, peripheral neuropathy was reported in 9 patients (none were grade 3). Transcription profiling identified the prevalence of genes associated with ribonucleoprotein complexes, RNA processing, and protein translation. The gene expression changes were more robust in patients who responded or had stable disease compared with patients who had progressive disease. Conclusions: The combination of bortezomib and PLD was well tolerated, but the antitumor activity is insufficient to warrant further investigation in ovarian cancer.