Dose-escalation study of fixed-dose rate gemcitabine combined with capecitabine in advanced solid malignancies.

Objective: To define dose limiting toxicities (DLTs) and the maximum tolerated dose (MTD) of capecitabine with fixed-dose rate (FDR) gemcitabine.

Methods: Eligible adults (advanced solid tumor; performance status

Results: Thirty patients (median age 59 years) were enrolled. The predominant grade >or=3 toxicity was myelosuppression, particularly neutropenia. At dose level 4 (1,000 mg/m(2) gemcitabine), two out of five evaluable patients had a DLT (grade 4 neutropenia >or=7 days). At dose level 3 (800 mg/m(2) gemcitabine), one patient had a DLT (grade 3 neutropenia >or=7 days) among six evaluable patients. Therefore, the MTD and recommended phase II dose was designated as capecitabine 500 mg/m(2) PO BID days 1-14 with 800 mg/m(2) FDR gemcitabine days 1 and 8 infused at 10 mg/m(2) per min on a 21-day cycle. Partial responses occurred in pretreated patients with esophageal, renal cell and bladder carcinomas.

Conclusions: This regimen was well tolerated and may deserve evaluation in advanced gastrointestinal and genitourinary carcinomas.