Phase I trial of fixed-dose rate gemcitabine in combination with bortezomib in advanced solid tumors

Background: Bortezomib demonstrates synergism with gemcitabine via a fixed-dose rate (FDR). The aim of this phase I trial in solid tumors was to establish the maximum tolerated dose (MTD) and safety data for this combination. Patients and Methods: Twenty-nine patients with a median age of 63 (range 36-84) years and median Karnofsky Performance Status of 90 (range 60-100) were enrolled and treated with bortezomib (1.0 or 1.3 mg/m²) on days 1, 4, 8 and 11 and FDR gemcitabine (750, 1,000, or 1,250 mg/m²) on days 1 and 8 of each 21-day cycle. Response was evaluated every two cycles. Results: Dose-limiting toxicities were grade 4 thrombocytopenia and neutropenia and grade 3 liver function test abnormalities. The MTD was bortezomib 1 mg/m2 and FDR gemcitabine 1,250 mg/m². The median number of cycles delivered was 3 (range 1-28). There was one partial response and six cases of stable disease. The median duration of response was 8.5 (range 3-20) months. Conclusion: FDR gemcitabine and bortezomib combination can be delivered effectively with acceptable toxicity.