Granulocyte-macrophage-colony stimulating factor in combination immunotherapy for patients with metastatic renal cell carcinoma

Results of two phase II clinical trials

Christopher Ryan, Nicholas J. Vogelzang, Mary C. Dumas, Timothy Kuzel, Walter M. Stadler

Research output: Contribution to journalArticle

25 Citations (Scopus)

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 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.

Original languageEnglish (US)
Pages (from-to)1317-1324
Number of pages8
JournalCancer
Volume88
Issue number6
DOIs
StatePublished - Mar 15 2000
Externally publishedYes

Fingerprint

Phase II Clinical Trials
Granulocyte-Macrophage Colony-Stimulating Factor
Renal Cell Carcinoma
Immunotherapy
Interleukin-2
Interleukin-11
Anorexia
Fatigue
Fever
Confidence Intervals
Isotretinoin
Mucositis
Hyperbilirubinemia
Dermatitis
Therapeutics
Nausea
Interferons
Vomiting
Survival Rate
Kidney

Keywords

  • 13-cis-retinoic acid
  • Granulocyte- macropage-colony stimulating factor
  • Interferon-alpha
  • Interleukin-2
  • Renal cell carcinoma

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Granulocyte-macrophage-colony stimulating factor in combination immunotherapy for patients with metastatic renal cell carcinoma : Results of two phase II clinical trials. / Ryan, Christopher; Vogelzang, Nicholas J.; Dumas, Mary C.; Kuzel, Timothy; Stadler, Walter M.

In: Cancer, Vol. 88, No. 6, 15.03.2000, p. 1317-1324.

Research output: Contribution to journalArticle

Ryan, Christopher ; Vogelzang, Nicholas J. ; Dumas, Mary C. ; Kuzel, Timothy ; Stadler, Walter M. / Granulocyte-macrophage-colony stimulating factor in combination immunotherapy for patients with metastatic renal cell carcinoma : Results of two phase II clinical trials. In: Cancer. 2000 ; Vol. 88, No. 6. pp. 1317-1324.
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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 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.",
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AU - Kuzel, Timothy

AU - Stadler, Walter M.

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N2 - 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.

AB - 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.

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