title: Granulocyte-macrophage-colony stimulating factor in combination immunotherapy for patients with metastatic renal cell carcinoma: results of two phase II clinical trials.
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.
authors.affiliation: Section of Hematology/Oncology, University of Chicago, Chicago, Illinois 60637, USA.
authors.forename: C W
authors.initials: CW
authors.lastname: Ryan
authors.forename: N J
authors.initials: NJ
authors.lastname: Vogelzang
authors.forename: M C
authors.initials: MC
authors.lastname: Dumas
authors.forename: T
authors.initials: T
authors.lastname: Kuzel
authors.forename: W M
authors.initials: WM
authors.lastname: Stadler
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000855:Anorexia / Q000209:etiology; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D002292:Carcinoma, Renal Cell / Q000556:secondary* / Q000628:therapy; D016001:Confidence Intervals; D005221:Fatigue / Q000209:etiology; D005260:Female; D005334:Fever / Q000209:etiology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D007167:Immunotherapy; D007279:Injections, Subcutaneous; D016898:Interferon-alpha / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D007376:Interleukin-2 / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D015474:Isotretinoin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D007680:Kidney Neoplasms / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D018714:Radiotherapy, Adjuvant; D012074:Remission Induction; D015996:Survival Rate
chemical_list: D000970:Antineoplastic Agents; D016898:Interferon-alpha; D007376:Interleukin-2; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D015474:Isotretinoin