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 t oxicity of two regimens containing granulocyte-macrophage-colony stimulatin g 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 irradiatio n to the primary tumor or metastatic site, followed by GM-CSF 100 mu g/day administered subcutaneously (sc) for 2 weeks and IL-2 11 x 10(6) IU sc 4 da ys per week for 4 weeks. In the second trial (Trial 2), the therapy consist ed of GM-CSF 125 mu g/day sc for 2 weeks, followed by IL-2 11 x 106 IU sc 4 days per week and interferon-alpha 10 X 106 IU sc 2 days per week for 4 we eks, 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 patien ts had stable disease. There was 1 partial responder (5%) of 20 evaluable p atients in Trial 2 who achieved a complete response with surgical resection . An additional 3 patients maintained stable disease, 2 of whom were render ed disease free by resection of the renal primary and a single metastatic s ite. 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 toxicit ies included fever, fatigue, anorexia, nausea/vomiting, hyperbilirubinemia, and mental status change. Toxicity was more frequent in Trial 2 and includ ed Grade 3 fever, fatigue, anorexia, mucositis, and dermatitis. One on-stud y death may have been therapy-related. CONCLUSIONS. GM-CSF does not enhance the low response rate of IL-2-based im munotherapy for patients with metastatic renal cell carcinoma. New active a gents are needed to treat patients with this disease. Cancer 2000;88:1317-2 4. (C) 2000 American Cancer Society.