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

TY - JOUR

T1 - Phase II activity of belinostat (PXD-101), carboplatin, and paclitaxel in women with previously treated ovarian cancer

AU - Dizon, Don S

AU - Damstrup, Lars

AU - Finkler, Neil J

AU - Lassen, Ulrik

AU - Celano, Paul

AU - Glasspool, Ros

AU - Crowley, Elizabeth

AU - Lichenstein, Henri S

AU - Knoblach, Poul

AU - Penson, Richard T

PY - 2012/7

Y1 - 2012/7

N2 - 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/m 2 daily for 5 days with carboplatin, AUC 5; and paclitaxel, 175 mg/m 2 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%Y61%). When stratified by primary platinum status, the ORR was 44% among resistant patients and 63% among sensitive patients. The most common drugrelated 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%Y66%). Median overall survival was not reached during study follow-up. Conclusions: Belinostat, carboplatin, and paclitaxel combinedwas reasonablywell 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.

AB - 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/m 2 daily for 5 days with carboplatin, AUC 5; and paclitaxel, 175 mg/m 2 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%Y61%). When stratified by primary platinum status, the ORR was 44% among resistant patients and 63% among sensitive patients. The most common drugrelated 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%Y66%). Median overall survival was not reached during study follow-up. Conclusions: Belinostat, carboplatin, and paclitaxel combinedwas reasonablywell 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.

KW - Adult

KW - Aged

KW - Aged, 80 and over

KW - Antineoplastic Agents, Phytogenic

KW - Antineoplastic Combined Chemotherapy Protocols

KW - Carboplatin

KW - Carcinoma

KW - Female

KW - Humans

KW - Hydroxamic Acids

KW - Middle Aged

KW - Neoplasm Recurrence, Local

KW - Ovarian Neoplasms

KW - Paclitaxel

KW - Sulfonamides

KW - Clinical Trial, Phase II

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1097/igc.0b013e31825736fd

DO - 10.1097/igc.0b013e31825736fd

M3 - Journal article

C2 - 22694911

SN - 1048-891X

VL - 22

SP - 979

EP - 986

JO - International Journal of Gynecological Cancer

JF - International Journal of Gynecological Cancer

IS - 6

ER -