Response of combination platinum and gemcitabine chemotherapy for recurrent epithelial ovarian carcinoma

Abstract

Objective. It has been postulated that gemcitabine inhibits DNA repair, and platinum resistance is due to increased DNA repair activity. The addition of gemcitabine to platinum-based agents may have synergistic tumoricidal activity. Methods. Retrospective chart review of all patients with recurrent, persistent, or progressive fallopian tube or ovarian carcinoma treated with a platinum-based compound and gemcitabine from 2001 to present was performed. Results. Twenty-nine patients on second to eight line chemotherapy met inclusion criteria. The median age was 53 years. Twenty-two patients received cisplatin and gemcitabine, and 7 patients received carboplatin and gemcitabine based on results of chemoresistance assays or prior chemorelated toxicities. The intent to treat was with six cycles of gemcitabine (1000 mg/m 2) and either cisplatin (75 mg/m 2) or carboplatin (AUC 5) day 1 and gemcitabine only on day 8 of a 21-day cycle. The median number of cycles administered was six. There were 20 grade 3 and 4 toxicities and 63% of patients by cycle 6 needed erythropoietin marrow support and 19% needed GCSF support by cycle 4. Twenty-one patients required discontinuation of day 8 that most commonly occurred at cycle 4. Eleven (38%) had CR, 5 (17%) had PR, 6 (21%) had SD, and 7 (24%) had PD, which is a 55% overall response. Nineteen of 29 patients (66%) showed platinum resistance to initial therapy. Of those, four (21%) had CR, four (21%) had PR, six (32%) had SD, and five (26%) with PD, which demonstrates a 42% overall response rate for this particular subset of patients. Conclusions. Adjuvant combination platinum-based agent with gemcitabine is a very effective and well-tolerated treatment for recurrent fallopian tube or ovarian carcinoma; even in those who exhibit initial platinum resistance.