A multicenter phase II study of thalidomide in combination with interleukin-2 (IL-2) in patients with previously untreated metastatic renal cell carcinoma (MRCC)

Abstract

14636 Background: Thalidomide, a drug with immune modulating and anti-angiogenic properties has shown activity in relapsed/refractory MRCC; furthermore, early phase I data of oral thalidomide with subcutaneous low-dose IL-2 showed the combination to be safe. The potential anti-tumor activity of this combination formed the basis of this study. Methods: The aim of this multi-center, open label, phase II study was to determine the efficacy and safety of thalidomide and IL-2 given in combination. Patients (pts) with untreated clear cell MRCC with measurable disease and previous nephrectomy were eligible. Two 6-week cycles of thalidomide and IL-2 were planned. Each cycle consisted of thalidomide started at 200 mg orally daily and titrated to 400 mg daily on the 4th day for 6 weeks; IL-2 was started one week post initiation of thalidomide at a dose of 7mIU/m2 subcutaneously days 1–5 for 4 weeks, followed by 2 weeks off therapy. Therapy was to be continued until progression, if there was at least stable disease (SD). Planned accrual was 53 patients. Results: 11 pts were enrolled. The trial was terminated early due to lack of responses. Median age was 57 years (51–66). All pts had an Eastern Cooperative Oncology Group performance status of 2 or better. The only grade 3 toxicities were fatigue (3 pts), neuropathy (1 pt), anorexia (1 pt), dyspnea (1 pt), edema (1 pt); these required dose reductions as per protocol. There were no objective responses: 3 pts had SD, 8 pts had progressive disease (PD). The 3 pts with SD completed 4, 4, and 6 cycles of therapy respectively; of the 8 pts with PD, 3 completed two cycles, and 5 completed one cycle of therapy. Conclusions: The combination of thalidomide and low-dose IL-2 was well tolerated, but in this trial did not show anti-tumor activity in patients with clear cell MRCC. We thank Celgene for support of this trial. No significant financial relationships to disclose.