کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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6184497 | 1600075 | 2013 | 7 صفحه PDF | دانلود رایگان |

- Study with weekly fixed dose rate gemcitabine plus carboplatin in ovarian carcinoma after first line therapy (28Â day schedule)
- Population pharmacokinetic modeling shows that increase of carboplatin dose requires decrease of fixed dose rate gemcitabine dose and vice versa.
- Carboplatin plus fixed dose rate gemcitabine as a weekly schedule in ovarian carcinoma results in increased myelosuppression.
ObjectiveThis phase I study of fixed dose rate (FDR) gemcitabine and carboplatin assessed the maximum tolerated dose (MTD), dose-limiting toxicities (DLTs), safety, pharmacokinetic (PK)/pharmacodynamic (PD) profile and preliminary anti-tumor activity in patients with recurrent ovarian cancer (OC).MethodsPatients with recurrent OC after first line treatment were treated with carboplatin and FDR gemcitabine (infusion speed 10Â mg/m2/min) on days 1, 8 and 15, every 28Â days. Pharmacokinetics included measurement of platinum concentrations in plasma ultrafiltrate (pUF) and plasma concentrations of gemcitabine (dFdC) and metabolite dFdU. Intracellular levels of dFdC triphosphate (dFdC-TP), the most active metabolite of gemcitabine, were determined in peripheral blood mononuclear cells (PBMCs). Population pharmacokinetic modeling and simulation were performed to further investigate the optimal schedule.ResultsTwenty three patients were enrolled. Initial dose escalation was performed using FDR gemcitabine 300Â mg/m2 (administered at infusion speed of 10Â mg/m2/min) combined with carboplatin AUC 2.5 and 3. Excessive bone marrow toxicity led to a modified dose escalation schedule: carboplatin AUC 2 and dose escalation of FDR gemcitabine (300Â mg/m2, 450Â mg/m2, 600Â mg/m2 and 800Â mg/m2). DLT criteria as defined per protocol prior to the study were not met with carboplatin AUC 2 in combination with FDR gemcitabine 300-800Â mg/m2 because of myelosuppressive dose-holds (especially thrombocytopenia and neutropenia).ConclusionsFDR gemcitabine in combination with carboplatin administered in this 28Â days schedule resulted in increased grade 3/4 toxicity compared to conventional 30-minute infused gemcitabine. A two weekly schedule (chemotherapy on days 1 and 8) would be more appropriate.
Journal: Gynecologic Oncology - Volume 130, Issue 3, September 2013, Pages 511-517