A retrospective evaluation of activity of gemcitabine/platinum regimens in the treatment of recurrent ovarian cancer.

Background: While many of these agents have been compared in prospective clinical trials, the gemcitabine/platinumbased regimens have not been compared in a prospective, randomized clinical trial. While bothgemcitabine/carboplatin and gemcitabine/cisplatin have a similar ORR in separate clinical trials, the tworegimens have never been directly been compared. With overlapping dose-limiting toxicity of thrombocytopenia, the gemcitabine/carboplatin regimen has been challenging to employ in the clinical setting in previously treated ovarian cancer patients and is often associated with treatment delays and/or dose reductions. Gemcitabine/cisplatin can also be a challenge due to its dose limiting neuropathy and renal toxicity, especially in previously treated patients. In the absence of any prospective, head to head comparison this retrospective study was embarked upon to compare the response rate and toxicity profiles of gemcitabine/cisplatin verses gemcitabine/carboplatin for the treatment of platinum-sensitive verses platinum-resistant recurrent ovarian cancer.

Methods: This was a retrospective chart review study that identified patients that had received either gemcitabine/cisplatin or gemcitabine/carboplatin for treatment of recurrent ovarian cancer and compared documented hematological and non-hematological toxicity and response based on RECIST (v1.1). Data was evaluated based upon platinum sensitivity/resistance as well.

Results: A total of 93 patients were identified that had received a gemcitabine/platinum regimen with 48 with recurrent ovarian cancer that were included in the study. There were 21 patients in the gemcitabine/cisplatin arm and 27 patients identified in the gemcitabine/carboplatin arm. Objective response rate (ORR) was greater in platinum-sensitive patients that received gemcitabine/carboplatin compared to gemcitabine/cisplatin (8 (67%) vs 2 (25%), p  < 0.05). Conversely, ORR was greater in platinum-resistant patients treated with gemcitabine/cisplatin (4 (57%) vs 1 (25%), NS). Mean time to progression was greater in gemcitabine/cisplatin patients (7.2 vs 5.1 months, p  < 0.03). Patients treated with gemcitabine/carboplatin discontinued due to toxicity at a greater rate (8 (33%) vs 5 (24%)). Specifically gemcitabine/carboplatin had a greater incidence (85%) of grade 2 or greater leukopenia, thrombocytopenia, and neutropenia compared to gemcitabine/cisplatin (19%) However, there was no significant difference in dose reductions, treatment delays, or granulocyte-colony stimulating factor (G-CSF) administration between regimens.

Conclusions: Gemcitabine/cisplatin appears to have greater efficacy in platinum-resistant patients, while gemcitabine/carboplatin seems to have greater efficacy in platinum-sensitive patients. Overall, gemcitabine/carboplatin was associated with a greater incidence of myelosuppression and discontinuation due to toxicity. Similar to findings in endometrial cancer, gemcitabine/cisplatin may have benefit specifically in platinum-resistant ovarian cancer.