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

Abstract

4717 Background: Thalidomide’s immunomodulatory and anti-angiogenic effects may augment the antitumor activity of IL-2. The early efficacy and safety findings observed in low dose subcutaneous (SQ) IL-2/thalidomide combination therapy for treatment of MRCC (ASCO, 2003) form the foundation for the current study. GM-CSF is an important cytokine for the generation and propagation of antigen presenting cells and for priming cellular immune responses. The primary objective is to improve the antitumor activity by adding GM-CSF to the thalidomide plus IL-2 regimen. Methods: Eligibility: histologic diagnosis of confirmed clear cell carcinoma, excluding papillary, sarcomatoid, or collecting duct tumors, measurable MRCC, normal organ/marrow function, life expectancy ≥12 weeks, Zubrod performance status (ZPS) ≤2, no prior chemo or immunotherapy, no active CNS involvement. Wk 0, thalidomide was administered orally at 200mg and increased to 400mg after 48 hrs, IL-2 at 7mIu/m2 and GM-CSF at 250mcg/m2 were injected SQ, starting at wk 1, days 1–5, wks 1–4, with a rest period at wks 5, 6. Response was assessed every 2 therapy cycles. Stable or responding pts completed 6 cycles, then were placed on maintenance thalidomide. Six pts are inevaluable for response secondary to CNS toxicity, non-compliance, or early progressive disease. Pt characteristics: 21 male/7 female, aged 57–73 (median 64) years; 28 pts had confirmed RCC. All pts had metastatic involvement. Sites included: lung (N=24), nodal (N=6), liver (N=5), bone (N=2), kidney (N=1), eye (N=1). Number of metastatic sites: 1 (N=16), 2 (N=9), 3 (N=3). ZPS 0 (N=25) and ZPS 1 (N=3). Results: 28 pts were enrolled: 3 complete responses, 6 partial, 6 stable, 7 progressive disease, and 6 not evaluable. Grade 1/2 toxicity included: somnolence, constipation, rash, flu-like symptoms, fluid retention, hypotension, hypothyroidism, sinus bradycardia, and peripheral neuropathy. Hematologic changes consisted of: leukocytosis associated with neutropenia, lymphocytosis and eosinophilia. Conclusion: Enrollment is ongoing. Data regarding response rate, time to progression, and toxicity will be presented. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Celgene, Chiron Celgene, Chiron, Endocyte