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.
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.
Authors: Hui Zhang; Tao Liu; Zhen Zhang; Samuel H Payne; Bai Zhang; Jason E McDermott; Jian-Ying Zhou; Vladislav A Petyuk; Li Chen; Debjit Ray; Shisheng Sun; Feng Yang; Lijun Chen; Jing Wang; Punit Shah; Seong Won Cha; Paul Aiyetan; Sunghee Woo; Yuan Tian; Marina A Gritsenko; Therese R Clauss; Caitlin Choi; Matthew E Monroe; Stefani Thomas; Song Nie; Chaochao Wu; Ronald J Moore; Kun-Hsing Yu; David L Tabb; David Fenyö; Vineet Bafna; Yue Wang; Henry Rodriguez; Emily S Boja; Tara Hiltke; Robert C Rivers; Lori Sokoll; Heng Zhu; Ie-Ming Shih; Leslie Cope; Akhilesh Pandey; Bing Zhang; Michael P Snyder; Douglas A Levine; Richard D Smith; Daniel W Chan; Karin D Rodland Journal: Cell Date: 2016-06-29 Impact factor: 41.582
Authors: Thehang Luu; Paul Frankel; Jan H Beumer; Dean Lim; Mihaela Cristea; Leonard J Appleman; Heinz J Lenz; David R Gandara; Brian F Kiesel; Richard L Piekarz; Edward M Newman Journal: Cancer Chemother Pharmacol Date: 2019-09-14 Impact factor: 3.333
Authors: Robert Brown; Edward Curry; Luca Magnani; Charlotte S Wilhelm-Benartzi; Jane Borley Journal: Nat Rev Cancer Date: 2014-09-25 Impact factor: 60.716
Authors: Javier Martinez-Useros; Mario Martin-Galan; Maria Florez-Cespedes; Jesus Garcia-Foncillas Journal: Cancers (Basel) Date: 2021-06-27 Impact factor: 6.639