A phase II trial of intravenous gemcitabine and 5-fluorouracil with subcutaneous interleukin-2 and interferon-α in patients with metastatic renal cell carcinoma

Christopher Ryan, Nicholas J. Vogelzang, Walter M. Stadler

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

BACKGROUND. The objective of this study was to determine the response rate and toxicity of gemcitabine and continuous-infusion 5-fluorouracil (5-FU) in combination with subcutaneous interleukin-2 (IL2) and interferon-α (IFNA) in patients with metastatic renal cell carcinoma. METHODS. Forty-one patients were treated with gemcitabine 600 mg/m2 on Days 1, 8, and 15 and continuous-infusion 5-FU on Days 1-21. The dose of 5-FU was 200 mg/m2 per day for the initial 8 patients but was reduced to 150 mg/m2 per day for all remaining patients due to toxicity. Starting on Day 15, IL2 and IFNA were administered for 4 weeks. IL2 was administered at a dose of 11 x 106 IU subcutaneously (sc) 4 days per week and IFNA was administered at a dose of 10.0 x 106 IU sc 2 days per week. RESULTS. Of 41 patients enrolled in the study, there was 1 complete response (CR), and there were 5 partial responses (PR), for an overall response rate of 14.6% (90% confidence interval [90%CI], 6.6-26.9%). The median time to disease progression was 6.6 months (90%CI, 3.9-7.5 months), and the median overall survival was 20.6 months (90%CI, 9.6-23.3 months). Toxicity was moderate to severe, with fatigue, fever, anorexia, or nausea experienced by 75-90% of patients. Mucositis and neutropenia, likely due to the gemcitabine and 5-FU, were experienced by a majority of patients. CONCLUSIONS. The addition of gemcitabine and 5-FU to subcutaneous IL2 and IFNA results in a similar response rate to what was observed in previous studies of IL2-based therapy. The toxicity of this four-drug combination is significant, and the regimen is not recommended for further development.

Original languageEnglish (US)
Pages (from-to)2602-2609
Number of pages8
JournalCancer
Volume94
Issue number10
DOIs
StatePublished - May 15 2002
Externally publishedYes

Fingerprint

gemcitabine
Renal Cell Carcinoma
Fluorouracil
Interferons
Interleukin-2
Confidence Intervals
Mucositis
Anorexia
Drug Combinations
Neutropenia
Nausea
Fatigue
Disease Progression
Fever

Keywords

  • 5-Fluorouracil
  • Chemotherapy
  • Gemcitabine
  • Immunotherapy
  • Interferon-α
  • Interleukin-2
  • Renal carcinoma

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

A phase II trial of intravenous gemcitabine and 5-fluorouracil with subcutaneous interleukin-2 and interferon-α in patients with metastatic renal cell carcinoma. / Ryan, Christopher; Vogelzang, Nicholas J.; Stadler, Walter M.

In: Cancer, Vol. 94, No. 10, 15.05.2002, p. 2602-2609.

Research output: Contribution to journalArticle

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title = "A phase II trial of intravenous gemcitabine and 5-fluorouracil with subcutaneous interleukin-2 and interferon-α in patients with metastatic renal cell carcinoma",
abstract = "BACKGROUND. The objective of this study was to determine the response rate and toxicity of gemcitabine and continuous-infusion 5-fluorouracil (5-FU) in combination with subcutaneous interleukin-2 (IL2) and interferon-α (IFNA) in patients with metastatic renal cell carcinoma. METHODS. Forty-one patients were treated with gemcitabine 600 mg/m2 on Days 1, 8, and 15 and continuous-infusion 5-FU on Days 1-21. The dose of 5-FU was 200 mg/m2 per day for the initial 8 patients but was reduced to 150 mg/m2 per day for all remaining patients due to toxicity. Starting on Day 15, IL2 and IFNA were administered for 4 weeks. IL2 was administered at a dose of 11 x 106 IU subcutaneously (sc) 4 days per week and IFNA was administered at a dose of 10.0 x 106 IU sc 2 days per week. RESULTS. Of 41 patients enrolled in the study, there was 1 complete response (CR), and there were 5 partial responses (PR), for an overall response rate of 14.6{\%} (90{\%} confidence interval [90{\%}CI], 6.6-26.9{\%}). The median time to disease progression was 6.6 months (90{\%}CI, 3.9-7.5 months), and the median overall survival was 20.6 months (90{\%}CI, 9.6-23.3 months). Toxicity was moderate to severe, with fatigue, fever, anorexia, or nausea experienced by 75-90{\%} of patients. Mucositis and neutropenia, likely due to the gemcitabine and 5-FU, were experienced by a majority of patients. CONCLUSIONS. The addition of gemcitabine and 5-FU to subcutaneous IL2 and IFNA results in a similar response rate to what was observed in previous studies of IL2-based therapy. The toxicity of this four-drug combination is significant, and the regimen is not recommended for further development.",
keywords = "5-Fluorouracil, Chemotherapy, Gemcitabine, Immunotherapy, Interferon-α, Interleukin-2, Renal carcinoma",
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T1 - A phase II trial of intravenous gemcitabine and 5-fluorouracil with subcutaneous interleukin-2 and interferon-α in patients with metastatic renal cell carcinoma

AU - Ryan, Christopher

AU - Vogelzang, Nicholas J.

AU - Stadler, Walter M.

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Y1 - 2002/5/15

N2 - BACKGROUND. The objective of this study was to determine the response rate and toxicity of gemcitabine and continuous-infusion 5-fluorouracil (5-FU) in combination with subcutaneous interleukin-2 (IL2) and interferon-α (IFNA) in patients with metastatic renal cell carcinoma. METHODS. Forty-one patients were treated with gemcitabine 600 mg/m2 on Days 1, 8, and 15 and continuous-infusion 5-FU on Days 1-21. The dose of 5-FU was 200 mg/m2 per day for the initial 8 patients but was reduced to 150 mg/m2 per day for all remaining patients due to toxicity. Starting on Day 15, IL2 and IFNA were administered for 4 weeks. IL2 was administered at a dose of 11 x 106 IU subcutaneously (sc) 4 days per week and IFNA was administered at a dose of 10.0 x 106 IU sc 2 days per week. RESULTS. Of 41 patients enrolled in the study, there was 1 complete response (CR), and there were 5 partial responses (PR), for an overall response rate of 14.6% (90% confidence interval [90%CI], 6.6-26.9%). The median time to disease progression was 6.6 months (90%CI, 3.9-7.5 months), and the median overall survival was 20.6 months (90%CI, 9.6-23.3 months). Toxicity was moderate to severe, with fatigue, fever, anorexia, or nausea experienced by 75-90% of patients. Mucositis and neutropenia, likely due to the gemcitabine and 5-FU, were experienced by a majority of patients. CONCLUSIONS. The addition of gemcitabine and 5-FU to subcutaneous IL2 and IFNA results in a similar response rate to what was observed in previous studies of IL2-based therapy. The toxicity of this four-drug combination is significant, and the regimen is not recommended for further development.

AB - BACKGROUND. The objective of this study was to determine the response rate and toxicity of gemcitabine and continuous-infusion 5-fluorouracil (5-FU) in combination with subcutaneous interleukin-2 (IL2) and interferon-α (IFNA) in patients with metastatic renal cell carcinoma. METHODS. Forty-one patients were treated with gemcitabine 600 mg/m2 on Days 1, 8, and 15 and continuous-infusion 5-FU on Days 1-21. The dose of 5-FU was 200 mg/m2 per day for the initial 8 patients but was reduced to 150 mg/m2 per day for all remaining patients due to toxicity. Starting on Day 15, IL2 and IFNA were administered for 4 weeks. IL2 was administered at a dose of 11 x 106 IU subcutaneously (sc) 4 days per week and IFNA was administered at a dose of 10.0 x 106 IU sc 2 days per week. RESULTS. Of 41 patients enrolled in the study, there was 1 complete response (CR), and there were 5 partial responses (PR), for an overall response rate of 14.6% (90% confidence interval [90%CI], 6.6-26.9%). The median time to disease progression was 6.6 months (90%CI, 3.9-7.5 months), and the median overall survival was 20.6 months (90%CI, 9.6-23.3 months). Toxicity was moderate to severe, with fatigue, fever, anorexia, or nausea experienced by 75-90% of patients. Mucositis and neutropenia, likely due to the gemcitabine and 5-FU, were experienced by a majority of patients. CONCLUSIONS. The addition of gemcitabine and 5-FU to subcutaneous IL2 and IFNA results in a similar response rate to what was observed in previous studies of IL2-based therapy. The toxicity of this four-drug combination is significant, and the regimen is not recommended for further development.

KW - 5-Fluorouracil

KW - Chemotherapy

KW - Gemcitabine

KW - Immunotherapy

KW - Interferon-α

KW - Interleukin-2

KW - Renal carcinoma

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