Granulocyte-macrophage-colony stimulating factor in combination immunotherapy for patients with metastatic renal cell carcinoma: Results of two phase II clinical trials

BACKGROUND. The aim of this study was to determine the response rates and toxicity of two regimens containing granulocyte-macrophage-colony stimulating factor (GM-CSF) in combination with interleukin-2 (IL-2) in the treatment of patients with metastatic renal cell carcinoma. METHODS. Therapy given in the first trial (Trial 1) consisted of irradiation to the primary tumor or metastatic site, followed by GM-CSF 100 μg/day administered subcutaneously (sc) for 2 weeks and IL-2 11 x 10⁶ IU sc 4 days per week for 4 weeks. In the second trial (Trial 2), the therapy consisted of GM-CSF 125 μg/day sc for 2 weeks, followed by IL-2 11 x 10⁶ IU sc 4 days per week and interferon-α 10 x 10⁶ IU sc 2 days per week for 4 weeks, plus oral 13-cis- retinoic acid 1 mg/kg daily for 4 weeks. RESULTS. There were no responses among 20 patients in Trial 1, but 3 patients had stable disease. There was 1 partial responder (5%) of 20 evaluable patients in Trial 2 who achieved a complete response with surgical resection. An additional 3 patients maintained stable disease, 2 of whom were rendered disease free by resection of the renal primary and a single metastatic site. The 1-year survival rate was 75% (95% confidence interval [CI], 50-89) in Trial 1 and 48% (95% CI, 20- 71) in Trial 2. In Trial 1, Grade 3 toxicities included fever, fatigue, anorexia, nausea/vomiting, hyperbilirubinemia, and mental status change. Toxicity was more frequent in Trial 2 and included Grade 3 fever, fatigue, anorexia, mucositis, and dermatitis. One on-study death may have been therapy-related. CONCLUSIONS. GM-CSF does not enhance the low response rate of IL-2-based immunotherapy for patients with metastatic renal cell carcinoma. New active agents are needed to treat patients with this disease. (C) 2000 American Cancer Society.