Phase II study of combination thalidomide/interleukin-2 therapy plus granulocyte macrophage-colony stimulating factor in patients with metastatic renal cell carcinoma.

OBJECTIVE: The early efficacy and safety findings observed with thalidomide plus low-dose Interleukin-2 (IL-2) combination therapy for the treatment of metastatic renal cell carcinoma (MRCC) formed the foundation for this study. Granulocyte macrophage-colony stimulating factor (GM-CSF) is an important cytokine for priming cellular immune responses. This study assessed whether GM-CSF would improve the response rate of MRCC patients to the thalidomide plus IL-2 regimen.

METHODS: Thirty-one patients with progressive MRCC without prior treatment were enrolled. They received initial doses of thalidomide 200 mg on day 1 (escalated to 400 mg after the first 48 hours), and fixed doses of IL-2 at 7 mIU/m2 and GM-CSF at 250 microg/m2 by subcutaneous injection on days 1 to 5 in weeks 2 to 5, followed by a 2-week rest. After the initial 7-week course, patients received up to 6 subsequent 6-week courses.

RESULTS: Seventeen (55%) patients experienced disease control, including 3 (10%) complete responses, 8 (26%) partial responses, and 6 (19%) cases of stable disease. Disease progression was observed in 14 (45%) patients. Survival ranged from 1 to 30+ months. Toxicities included somnolence, nausea, constipation, rash, flu-like symptoms, fluid retention, hypotension, and neuropathy.

CONCLUSION: Thalidomide plus IL-2 in combination with GM-CSF is tolerable and produces durable responses in patients with MRCC. GM-CSF, however, did not produce a response rate superior to that reported in previous studies of combination thalidomide/IL-2 therapy. Further development of the thalidomide plus IL-2 combination therapy will address patients who have received molecular-targeted agents, such as sunitinib and sorafenib, as first- or second-line therapy.