Phase II evaluation of phenoxodiol in combination with cisplatin or paclitaxel in women with platinum/taxane-refractory/resistant epithelial ovarian, fallopian tube, or primary peritoneal cancers.

INTRODUCTION: Chemoresistance is a major limitation in the treatment of ovarian cancer. Phenoxodiol is a novel biomodulator capable of reversing chemoresistance in vitro and in vivo. In this study, we determined the safety and efficacy of intravenous phenoxodiol in combination with cisplatin or paclitaxel in women with platinum/taxane-refractory/resistant ovarian cancers.

METHODS: Thirty-two patients were randomized to 1 of 2 treatment arms according to their previous responses: (1) platinum refractory/resistant, cisplatin (40 mg/m intravenous) weekly on day 2 + phenoxodiol (3 mg/kg) weekly on days 1 and 2 and (2) taxane refractory/resistant, paclitaxel (80 mg/m IV) weekly on day 2 and phenoxodiol (3 mg/kg) weekly on days 1 and 2. Patients continued on treatment until complete response, disease progression, unacceptable toxicity, or voluntary withdrawal.

RESULTS: There were no treatment-related deaths. There was only one treatment-related hospitalization and 2 grade 4 toxicities. In the cisplatin arm, there were 3 partial responses, 9 patients (56%) achieved stable disease, 4 (25%) progressed, and the overall best response rate was 19%. In the paclitaxel arm, there was one complete response and 2 partial responses, 8 patients (53%) achieved stable disease, 4 patients (27%) progressed, and the overall best response rate was 20%.

DISCUSSION: The combination of IV phenoxodiol with cisplatin or paclitaxel was well tolerated in this study. Cisplatin-phenoxodiol was particularly active and warrants further study in patients with platinum-resistant ovarian cancer.