Phase II Activity of Belinostat (PXD-101), Carboplatin, and Paclitaxel in Women With Previously Treated Ovarian Cancer Article

Industry Collaboration International Collaboration

cited authors

  • Dizon, Don S., Damstrup, Lars, Finkler, Neil J., Lassen, Ulrik, Celano, Paul, Glasspool, Ros, Crowley, Elizabeth, Lichenstein, Henri S., Knoblach, Poul, Penson, Richard T.

funding text

  • The study was fully supported by Topotarget and Curagen Corporation. Institutional funds received for clinical trial support: Glasspool, Dizon. Research funding from Topotarget: Penson Employee of Topotarget (makers of belinostat): Damstrup, Knoblauch, Lichenstein (previously employed),

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/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%-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.

Publication Date

  • July 1, 2012

webpage

published in

category

start page

  • 979

end page

  • 986

volume

  • 22

issue

  • 6

WoS Citations

  • 34

WoS References

  • 27