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

Cancer. 2000 Mar 15;88(6):1317-24.

Abstract

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 microg/day administered subcutaneously (sc) for 2 weeks and IL-2 11x10(6) IU sc 4 days per week for 4 weeks. In the second trial (Trial 2), the therapy consisted of GM-CSF 125 microg/day sc for 2 weeks, followed by IL-2 11x10(6) IU sc 4 days per week and interferon-alpha 10x10(6) 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.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Administration, Oral
  • Adult
  • Aged
  • Anorexia / etiology
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use
  • Carcinoma, Renal Cell / secondary*
  • Carcinoma, Renal Cell / therapy
  • Confidence Intervals
  • Fatigue / etiology
  • Female
  • Fever / etiology
  • Granulocyte-Macrophage Colony-Stimulating Factor / administration & dosage
  • Granulocyte-Macrophage Colony-Stimulating Factor / adverse effects
  • Granulocyte-Macrophage Colony-Stimulating Factor / therapeutic use*
  • Humans
  • Immunotherapy*
  • Injections, Subcutaneous
  • Interferon-alpha / administration & dosage
  • Interferon-alpha / adverse effects
  • Interferon-alpha / therapeutic use
  • Interleukin-2 / administration & dosage
  • Interleukin-2 / adverse effects
  • Interleukin-2 / therapeutic use
  • Isotretinoin / administration & dosage
  • Isotretinoin / adverse effects
  • Isotretinoin / therapeutic use
  • Kidney Neoplasms / therapy*
  • Male
  • Middle Aged
  • Radiotherapy, Adjuvant
  • Remission Induction
  • Survival Rate

Substances

  • Antineoplastic Agents
  • Interferon-alpha
  • Interleukin-2
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • Isotretinoin