Background: We have conducted a phase I trial to determine the maximum tolerated dose of gemcitabine in combination with interferon, thalidomide and capecitabine.
Methods: Patients received oral capecitabine 1,000 mg/m(2 )per day, divided in 2 daily doses, 2 weeks on, 1 week off; subcutaneous interferon-alpha 1 mIU twice a day without an interruption; daily oral thalidomide 200 mg/day for the first 7 days, then escalated to 400 mg/day without an interruption. Gemcitabine was given by intravenous administration over 30 min on day 1, week 1 and day 8, week 2. Initial dose level of gemcitabine was 400 mg/m(2). The dose of gemcitabine was the phase I variable. One cycle was 3 weeks.
Results and discussion: We treated 12 patients, 6 patients were entered at a dose level of 0 (gemcitabine 400 mg/m(2)) and 6 patients entered at a dose level-1 (gemcitabine 200 mg/m(2)). Eight of 12 patients completed at least 12 weeks of therapy. Three partial responses and two stable disease were observed. The remaining patients had progressive disease. Non-hematologic toxicity was either grade 1 or 2. Hematologic toxicity at dose level 0 consisted of 3 patients with grade 3/4 neutropenia, and 1 patient with grade 3 thrombocytopenia. At dose level-1 grade 1/2 neutropenia was observed.
Conclusions: The completion of our phase I experience determined our maximum tolerated dose to be dose level-1. The phase II trial is currently being proposed for patients with rapidly growing clear cell, other histologies that may contain sarcomatoid elements or collecting duct tumor.