Dose-escalation study of fixed-dose rate gemcitabine combined with capecitabine in advanced solid malignancies
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- Attia, S., Morgan-Meadows, S., Holen, K.D. et al. Cancer Chemother Pharmacol (2009) 64: 45. doi:10.1007/s00280-008-0844-1
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To define dose limiting toxicities (DLTs) and the maximum tolerated dose (MTD) of capecitabine with fixed-dose rate (FDR) gemcitabine.
Eligible adults (advanced solid tumor; performance status ≤2) received capecitabine 500 mg/m2 PO BID days 1–14 and FDR gemcitabine (400–1,000 mg/m2 escalated by 200 mg/m2 increments) at 10 mg/m2/min days 1 and 8 on a 21-day cycle. A traditional 3 + 3 cohort design was used to determine the MTD.
Thirty patients (median age 59 years) were enrolled. The predominant grade ≥3 toxicity was myelosuppression, particularly neutropenia. At dose level 4 (1,000 mg/m2 gemcitabine), two out of five evaluable patients had a DLT (grade 4 neutropenia ≥7 days). At dose level 3 (800 mg/m2 gemcitabine), one patient had a DLT (grade 3 neutropenia ≥7 days) among six evaluable patients. Therefore, the MTD and recommended phase II dose was designated as capecitabine 500 mg/m2 PO BID days 1–14 with 800 mg/m2 FDR gemcitabine days 1 and 8 infused at 10 mg/m2 per min on a 21-day cycle. Partial responses occurred in pretreated patients with esophageal, renal cell and bladder carcinomas.
This regimen was well tolerated and may deserve evaluation in advanced gastrointestinal and genitourinary carcinomas.