Phase I/II study of thalidomide in combination with interleukin-2 in patients with metastatic renal cell carcinoma

The purpose of the study was to determine, in a Phase I/II study, the efficacy and safety profile of thalidomide with interleukin-2 (IL-2) in patients with metastatic renal cell carcinoma (MRCC).

Fifteen patients (8 of whom were previously treated) enrolled in Phase I were treated with escalating doses of oral thalidomide (200-600 mg) and a fixed dose of IL-2 (7 mIU/m(2)) by subcutaneous injection. A course was 6 weeks, with the exception of Course 1, which was 7 weeks. Thirty-seven Phase II patients who had not received prior chemotherapy or immunotherapy for renal cell carcinoma (RCC) received an initial thalidomide dose of 200 mg at Week 0, which was escalated to 400 mg after 48 hours. Subcutaneous IL-2 was administered at the same fixed daily dose used in Phase I.

Fifty-one of 52 Phase I/II patients were evaluable. Twenty-seven patients (52%) experienced disease control, including 4 (8%) complete responses, 15 (29%) partial responses, and 8 (15%) cases of stable disease. Disease progression was observed in 24 patients (47%). Survival in the 2 phases ranged from 4 weeks to 45.2+ months. At the time of last follow-up, 2 of 51 patients (4%) remained on maintenance thalidomide therapy and continue to be followed. Three of the 51 patients with CRs (6%) ceased thalidomide therapy at 23-25 months and have maintained their responses to date. One complete responder was lost to follow-up. As of January 2005, 14 of 51 patients (27%) remained alive. Toxicities were mild to moderate, including Grade 1 to 2 somnolence, constipation, neuropathy, rash, flu-like symptoms, fluid retention, hypotension, and hypothyroidism (according to version 2.0 of National Cancer Institute Common Toxicity Criteria). In addition, two patients experienced deep venous thrombosis.

Thalidomide in combination with IL-2 is tolerable and can produce durable, active responses in patients with MRCC. To evaluate the merits of thalidomide as a valuable agent against MRCC and to more fully determine the efficacy of thalidomide/IL-2 combination therapy, the scrutiny of Phase III testing is required. Further development of thalidomide/IL-2 combination therapy will be the focus of this group.