Phase II Study of thalidomide, Interleukin-2 (IL-2), and granulocyte macrophage-colony stimulating factor (GM-CSF) in patients with metastatic renal cell carcinoma (RCC)

Abstract

4702 Background: Thalidomide's anti-RCC activity, the potential that its immunomodulatory and anti-angiogenic effects may augment the antitumor activity of IL-2, and the promising early efficacy and safety findings observed with the combination of low dose sc IL-2 plus thalidomide therapy in the treatment of patients with metastatic RCC (ASCO, 2003) form the foundation for the current study. GM-CSF increases the number and activity of macrophages, which may provide a means to enhance the immune system against tumor cells, thus improving the antitumor activity of thalidomide plus IL-2. Methods: Eligibility includes histologic diagnosis of confirmed RCC excluding papillary, sarcomatoid, or collecting duct tumors, measurable disease, normal organ/marrow function, life expectancy >3 months, Zubrod performance status ≤ 2, no prior chemotherapy or immunotherapy, and no active CNS disease. Thalidomide was started at 200 mg after 48 hours to 400 mg at week zero. IL-2 at 7 mIu/m2 and GM-CSF at 250 mcg/m2 were given by subcutaneous injection, starting at week 1, days 1 through 5, weeks 1 through 4, with rest from IL-2 and GM-CSF at weeks 5 and 6. One cycle was 6 weeks. Response was assessed every 2 therapy cycles. 11 patients have been enrolled to date. One patient is inevaluable for response secondary to CNS toxicity and early removal from therapy. Patient characteristics; 11 male, 0 female, aged 57 - 73 (median 64) yrs were included; 11 pts had confirmed RCC. All patients had metastatic disease. Sites included: lung (N=10), nodal (N=3), liver (N=2), bone( N=1). Number of metastatic sites: 1 (N=8), 2 (N=1), 3 (N=2) Zubrod Performance Status: 0 (N= 11). Results: There has been 1 complete response and 9 pts are too early. Toxicities were generally grade 1–2 and included; somnolence, constipation, rash, flu-like symptoms associated with IL-2, fluid retention associated with the combination, hypotension (which was managed with oral fluids), hypothyroidism, sinus bradycardia, and peripheral neuropathy. Conclusions: Enrollment is ongoing, further data regarding response rate, time to progression, and toxicity will be presented. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Celgene