alexa Phase II activity of belinostat (PXD-101), carboplatin, and paclitaxel in women with previously treated ovarian cancer.
Pharmaceutical Sciences

Pharmaceutical Sciences

Journal of Clinical & Experimental Pharmacology

Author(s): Dizon DS, Damstrup L, Finkler NJ, Lassen U, Celano P,

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Abstract BACKGROUND: Preclinical data show that belinostat (Bel) is synergistic with carboplatin and paclitaxel in ovarian cancer. To further evaluate the clinical activity of belinostat, carboplatin, and paclitaxel (BelCaP), a phase 1b/2 study was performed, with an exploratory phase 2 expansion planned specifically for women with recurrent epithelial ovarian cancer (EOC). METHODS: Thirty-five women were treated on the phase 2 expansion cohort. BelCap was given as follows: belinostat, 1000 mg/m² daily for 5 days with carboplatin, AUC 5; and paclitaxel, 175 mg/m² given on day 3 of a 21-day cycle. The primary end point was overall response rate (ORR), using a Simon 2 stage design. RESULTS: The median age was 60 years (range, 39-80 years), and patients had received a median of 3 prior regimens (range, 1-4). Fifty-four percent had received more than two prior platinum-based combinations, sixteen patients (46\%) had primary platinum-resistant disease, whereas 19 patients (54\%) recurred within 6 months of their most recent platinum treatment. The median number of cycles of BelCaP administered was 6 (range, 1-23). Three patients had a complete response, and 12 had a partial response, for an ORR of 43\% (95\% confidence interval, 26\%-61\%). When stratified by primary platinum status, the ORR was 44\% among resistant patients and 63\% among sensitive patients. The most common drug-related adverse events related to BelCaP were nausea (83\%), fatigue (74\%), vomiting (63\%), alopecia (57\%), and diarrhea (37\%). With a median follow-up of 4 months (range, 0-23.3 months), 6-month progression-free survival is 48\% (95\% confidence interval, 31\%-66\%). Median overall survival was not reached during study follow-up. CONCLUSIONS: Belinostat, carboplatin, and paclitaxel combined was reasonably well tolerated and demonstrated clinical benefit in heavily-pretreated patients with EOC. The addition of belinostat to this platinum-based regimen represents a novel approach to EOC therapy and warrants further exploration. This article was published in Int J Gynecol Cancer and referenced in Journal of Clinical & Experimental Pharmacology

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