RT Journal Article
SR Electronic
T1 An Open-Label Phase 2 Study of Twice-Weekly Bortezomib and Intermittent Pegylated Liposomal Doxorubicin in Patients With Ovarian Cancer Failing Platinum-Containing Regimens
JF International Journal of Gynecologic Cancer
JO Int J Gynecol Cancer
FD BMJ Publishing Group Ltd
SP 792
OP 800
DO 10.1097/IGC.0b013e318251051a
VO 22
IS 5
A1 Gabriella Parma
A1 Rosanna Mancari
A1 Gianluca Del Conte
A1 Giovanni Scambia
A1 Angiolo Gadducci
A1 Dagmar Hess
A1 Dionyssios Katsaros
A1 Cristiana Sessa
A1 Andrea Rinaldi
A1 Francesco Bertoni
A1 Andrea Vitali
A1 Carlo Vittorio Catapano
A1 Silvia Marsoni
A1 Helgi van de Velde
A1 Nicoletta Colombo
YR 2012
UL http://ijgc.bmj.com/content/22/5/792.abstract
AB 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/m2 intravenous (days 1, 4, 8, and 11), and PLD, 30 mg/m2 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.