Retrospective review: re-treatment of patients with ovarian cancer with carboplatin after platinum resistance

Abstract

The objective of the analysis was to determine the effectiveness of re-treating patients with ovarian cancer, primary peritoneal cancer, and fallopian tube cancer with carboplatin after being deemed platinum resistant. From a database period January 1, 1996, to December 12, 2002, 34 patients were identified who received nonplatinum agents before resuming treatment with carboplatin. The median age was 65 years, and a median of two nonplatinum chemotherapy (range 1-5) prior to re-treatment with carboplatin was received. The median platinum-free interval from the time platinum was last received to re-treatment with carboplatin was 15.2 months (95% confidence interval [CI] 12.6-17.9; range 6.2-47.0). A median number of four cycles of carboplatin (range 1-11) was received. Two patients (5.9%) achieved partial response, while 21 patients (61.7%) achieved stable disease. The median time to progression for these 23 patients after re-treatment with carboplatin was 5.7 months (95% CI 5.2-6.3; range 1.8-15.3). Twenty-seven patients have died, and all patients have progressed. Seven patients are still receiving salvage therapy. The median overall survival from the time deemed to be platinum resistant is 23.2 months (95% CI 20.1-26.4). Patients who have been deemed platinum resistant may still benefit from platinum re-treatment after an interval of treatment with nonplatinum agents.

Treatment of recurrent ovarian cancer relapsing 6–12 months post platinum-based chemotherapy

“…The merit of extending the PFI using a non-platinum agent at relapse, thereby reversing or partially reversing platinum resistance and improving the subsequent response to platinum, has been postulated based on previously reported trial data [22,23]. There are several mechanisms by which tumors develop resistance to platinum, including increased efflux, enhanced DNA repair of damage caused by the platinum agent, and defective cell death pathways [24,25].…”

Recurrent Ovarian Cancer: When and How to Treat

“…No other phase 3 studies of combination regimens versus single agents have reported clinical outcomes in partially platinumsensitive patients, but there are solid data from several phase 2 studies demonstrating that response to platinum retreatment is related to the length of prior response to platinum-based therapy [35]. It has been postulated that patients with partially platinum-sensitive ROC may benefit from a strategy of extending the platinum-free interval by use of a non-platinum agent, followed by a platinum-based regimen at subsequent relapse [39,41]. This hypothesis is being addressed in a current clinical trial, INNOVATYON, where patients with partially platinum-sensitive ROC will be randomized to either trabectedin with PLD or carboplatin with PLD.…”

Combination of irinotecan and platinum for platinum-resistant or refractory recurrent ovarian cancers: A preliminary case series

“…After approval by the Institutional Review Board of the institution, a total of 28 patients with Pt-R ROC treated with CPT-Pt at the National Defense Medical College Hospital (Tokorowaza, Japan) between January, 2002 and December, 2012 were identified from a retrospective review of medical charts. All patients received combination therapy with TC as the first-line chemotherapy, and received CPT-Pt for the treatment of recurrent tumors with Pt-R. Platinum-resistance was sub-classified as follows (14,20): i) Platinum-refractory, patients who relapsed during TC therapy; ii) primary platinum-resistance, patients who relapsed within 6 months after the primary TC therapy; and iii) secondary platinum-resistance, patients who relapsed within 6 months after the second-line therapy with platinum-based regimen for the first relapse following primary TC therapy. From 2007, other regimens aside from five-day CPT-P were selected by clinicians according to kidney function and history of allergic reactions.…”

“…By contrast, dose-dense weekly administration of platinum agents has been reported to extend PFS for Pt-R ROC in recent years (12,13). Additionally, patients with Pt-R ROC may benefit again from platinum-based chemotherapy following the longer interval until platinum re-treatment with non-platinum single agents (14). Therefore, by modified method or timing of platinum administration, platinum re-treatment is potentially effective for Pt-R ROC.…”