A high rate of venous thromboembolism in a multi-institutional phase II trial of weekly intravenous gemcitabine with continuous infusion fluorouracil and daily thalidomide in patients with metastatic renal cell carcinoma

BACKGROUND. The objective of this study was to determine the clinical response rate of the combination of weekly intravenous (IV) gemcitabine with continuous infusion fluorouracil (5-FU) and daily oral thalidomide in patients with metastatic renal cell carcinoma (RCC). METHODS. Between June, 2000 and January, 2001, 21 patients with metastatic RCC were enrolled onto this multi-institutional Phase 11 study of gerncitabine at 600 mg/m(2) per day on Days 1, 8, and 15; 5-FU at 150 mg/m(2) per day by continuous IV infusion through a permanent catheter on Days 1-21; and oral thalidomide on Days 1-28 starting at a dose of 200 mg daily. After the first 2 weeks of therapy, the thalidomide dose was escalated by 100 mg per day every week to a maximum dose of 400 mg per day unless it was precluded by toxicity. Treatment cycles were repeated every 28 days. RESULTS. A high rate of venous thromboembolism (VTE) was observed. Five patients developed deep vein thrombosis (DVT), three patients developed pulmonary embolization (PE), and one patient suffered a fatal cardiac arrest preceded by hemoptysis, for an overall VTE rate of 43%. Of the 18 assessable patients, there were no complete responses and 2 partial responses (objective response rate, 10%; 95% confidence interval, 1-30%). CONCLUSIONS. The addition of thalidomide to gemcitabine and 5-FU did not improve the objective response rate previously observed with gemcitabine and 5-FU alone and added significant vascular toxicity. The authors recommend against further development or use of this three-drug regimen. (C) 2002 American Cancer Society.