By Bruce Sylvester
CHICAGO -- June 4, 2008 -- The addition of the investigative agent belinostat to a regimen combining carboplatin and paclitaxel is well tolerated and provides clinical benefit in heavily pretreated patients with relapsed epithelial ovarian cancer.
These findings were presented here on May 31 at the American Society of Clinical Oncology (ASCO) 44th Annual Meeting.
"The addition of belinostat increases the response rate even in patients who are resistant to platinum-based therapy. That is the most important finding here," said lead investigator Neil Finkler, MD, Florida Hospital Cancer Institute, Orlando, Florida.
According to Dr. Finkler and colleagues, preclinical data show that belinostat is synergistic with carboplatin and paclitaxel in platinum-sensitive and resistant models of ovarian cancer. Therefore, they conducted a phase 2 study to evaluate the efficacy of a combination of belinostat, carboplatin, and paclitaxel (BelCaP) in patients with relapsed epithelial ovarian cancer.
Patients had an Eastern Cooperative Oncology Group performance status of 0 to 2 and had been treated with 3 prior regimens for metastatic disease. All subjects had undergone prior platinum therapy; the median platinum-free interval was 12.5 months (range 0.6-60 months). Eleven subjects (31%) had relapsed within 6 month of their first platinum treatment.
The 35 enrolled subjects in this study had a median age of 60 years (range, 39-80) and a median duration of disease of 2.6 years (range, 0.3-8.7).
The primary endpoint was overall response of antitumour activity as assessed by Response Evaluation Criteria in Solid Tumours (RECIST) every 2 cycles of treatment.
Subjects underwent a median of 4 cycles (range 1-13) of treatment with BelCaP.
On days 1 to 5, subjects received belinostat 1000 mg/m2/day IV over 30 minutes. On day 3, patients received paclitaxel 175 mg/m2 IV over 3 hours, 2 to 3 hours after administration of belinostat. On day 3, patients received IV carboplatin at an area under the curve (mg/mL x min) of 5 over 30 to 60 minutes following paclitaxel administration.
Overall response was 43%, with a median time to response of 2.5 months (range, 1.1-4.0) and a median duration of response of >4.3 months. Seven responses were still ongoing.
Median progression-free survival in all 35 subjects (15 subjects have not progressed) was >5.4 months (range was >0.1 months to >12.6 months)
The investigators reported that the BelCaP regimen was well tolerated and presented a safety profile similar to what is seen with chemotherapy alone.
The authors concluded, "The addition of belinostat to platinum-based regimens represents a novel approach to the therapy of ovarian cancer. The substantial antitumour activity observed supports further development of BelCaP in patients with recurrent ovarian cancer."
"We think that we can overcome platinum resistance in these patients with the use of belinostat," Dr. Finkler added.
Funding for this study was provided by CuraGen Corporation.
[Presentation title: Phase II Multicenter Trial of the Histone Deactylase Inhibitor (HDACI) Belinostat, Carboplatin and Paclitaxel (BelCap) in Patients (Pts) With Relapsed Epithelial Ovarian Cancer (EOC). Abstract 5519]
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