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 II study of gemcitabine 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.