Interferon-alpha and survival in metastatic renal carcinoma

early results of a randomised controlled trial. Medical Research Council Renal Cancer Collaborators

Medical Research Council Renal Cancer Collaborators

Research output: Contribution to journalArticle

519 Citations (Scopus)

Abstract

BACKGROUND: Metastatic renal carcinoma has a 2-year survival of around 20% and is largely resistant to chemotherapy. The use of interferons in the treatment of metastatic renal carcinoma remains controversial. Although non-randomised studies suggest that biological therapy with interferons produces a small number of tumour responses, most clinicians judge such treatment to be ineffective. We have investigated the effect of treatment with interferon-alpha on survival in patients with metastatic renal carcinoma.

METHODS: In a multicentre, randomised trial, patients with metastatic renal carcinoma were randomly assigned subcutaneous interferon-alpha (three doses--5 MU, 5 MU, 10 MU--for the first week, then 10 MU three times per week for a further 11 weeks; n=174) or oral medroxyprogesterone acetate (MPA; 300 mg once daily for 12 weeks; n=176). The primary endpoint was overall survival. Analysis was by intention to treat. The trial used a triangular sequential design for early termination as soon as results were conclusive. The trial was stopped in November, 1997, when data were available for 335 patients (167 interferon-alpha, 168 MPA).

FINDINGS: A total of 111 patients have died in the interferon-alpha group, and 125 patients have died in the MPA group. There was a 28% reduction in the risk of death in the interferon-alpha group (hazard ratio 0.72 [95% CI 0.55-0.94], p=0.017). Interferon-alpha gave an improvement in 1-year survival of 12% (MPA 31% survival, interferon-alpha 43%), and an improvement in median survival of 2.5 months (MPA 6 months, interferon-alpha 8.5 months).

INTERPRETATION: The benefit of treatment with interferon-alpha should be weighed against the drug's toxic effects. Combination regimens of biological therapy and chemotherapy should now be compared with interferon-alpha monotherapy in randomised controlled trials.

Original languageEnglish
Pages (from-to)14-17
Number of pages4
JournalThe Lancet
Volume353
Issue number9146
DOIs
Publication statusPublished - 2 Jan 1999

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Kidney Neoplasms
Interferon-alpha
Biomedical Research
Randomized Controlled Trials
Carcinoma
Kidney
Survival
Biological Therapy
Interferons
Drug Therapy
Medroxyprogesterone Acetate
Intention to Treat Analysis
Poisons
Risk Reduction Behavior
Therapeutics
Multicenter Studies

Keywords

  • Aged
  • Antineoplastic Agents/therapeutic use
  • Antineoplastic Agents, Hormonal/therapeutic use
  • Carcinoma, Renal Cell/drug therapy
  • Female
  • Humans
  • Interferon-alpha/therapeutic use
  • Kidney Neoplasms/drug therapy
  • Male
  • Medroxyprogesterone Acetate/therapeutic use
  • Middle Aged
  • Neoplasm Metastasis
  • Nephrectomy
  • Registries
  • Survival Analysis
  • United Kingdom

Cite this

Interferon-alpha and survival in metastatic renal carcinoma : early results of a randomised controlled trial. Medical Research Council Renal Cancer Collaborators. / Medical Research Council Renal Cancer Collaborators.

In: The Lancet, Vol. 353, No. 9146, 02.01.1999, p. 14-17.

Research output: Contribution to journalArticle

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abstract = "BACKGROUND: Metastatic renal carcinoma has a 2-year survival of around 20{\%} and is largely resistant to chemotherapy. The use of interferons in the treatment of metastatic renal carcinoma remains controversial. Although non-randomised studies suggest that biological therapy with interferons produces a small number of tumour responses, most clinicians judge such treatment to be ineffective. We have investigated the effect of treatment with interferon-alpha on survival in patients with metastatic renal carcinoma.METHODS: In a multicentre, randomised trial, patients with metastatic renal carcinoma were randomly assigned subcutaneous interferon-alpha (three doses--5 MU, 5 MU, 10 MU--for the first week, then 10 MU three times per week for a further 11 weeks; n=174) or oral medroxyprogesterone acetate (MPA; 300 mg once daily for 12 weeks; n=176). The primary endpoint was overall survival. Analysis was by intention to treat. The trial used a triangular sequential design for early termination as soon as results were conclusive. The trial was stopped in November, 1997, when data were available for 335 patients (167 interferon-alpha, 168 MPA).FINDINGS: A total of 111 patients have died in the interferon-alpha group, and 125 patients have died in the MPA group. There was a 28{\%} reduction in the risk of death in the interferon-alpha group (hazard ratio 0.72 [95{\%} CI 0.55-0.94], p=0.017). Interferon-alpha gave an improvement in 1-year survival of 12{\%} (MPA 31{\%} survival, interferon-alpha 43{\%}), and an improvement in median survival of 2.5 months (MPA 6 months, interferon-alpha 8.5 months).INTERPRETATION: The benefit of treatment with interferon-alpha should be weighed against the drug's toxic effects. Combination regimens of biological therapy and chemotherapy should now be compared with interferon-alpha monotherapy in randomised controlled trials.",
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T1 - Interferon-alpha and survival in metastatic renal carcinoma

T2 - early results of a randomised controlled trial. Medical Research Council Renal Cancer Collaborators

AU - Fayers, Peter

AU - Medical Research Council Renal Cancer Collaborators

PY - 1999/1/2

Y1 - 1999/1/2

N2 - BACKGROUND: Metastatic renal carcinoma has a 2-year survival of around 20% and is largely resistant to chemotherapy. The use of interferons in the treatment of metastatic renal carcinoma remains controversial. Although non-randomised studies suggest that biological therapy with interferons produces a small number of tumour responses, most clinicians judge such treatment to be ineffective. We have investigated the effect of treatment with interferon-alpha on survival in patients with metastatic renal carcinoma.METHODS: In a multicentre, randomised trial, patients with metastatic renal carcinoma were randomly assigned subcutaneous interferon-alpha (three doses--5 MU, 5 MU, 10 MU--for the first week, then 10 MU three times per week for a further 11 weeks; n=174) or oral medroxyprogesterone acetate (MPA; 300 mg once daily for 12 weeks; n=176). The primary endpoint was overall survival. Analysis was by intention to treat. The trial used a triangular sequential design for early termination as soon as results were conclusive. The trial was stopped in November, 1997, when data were available for 335 patients (167 interferon-alpha, 168 MPA).FINDINGS: A total of 111 patients have died in the interferon-alpha group, and 125 patients have died in the MPA group. There was a 28% reduction in the risk of death in the interferon-alpha group (hazard ratio 0.72 [95% CI 0.55-0.94], p=0.017). Interferon-alpha gave an improvement in 1-year survival of 12% (MPA 31% survival, interferon-alpha 43%), and an improvement in median survival of 2.5 months (MPA 6 months, interferon-alpha 8.5 months).INTERPRETATION: The benefit of treatment with interferon-alpha should be weighed against the drug's toxic effects. Combination regimens of biological therapy and chemotherapy should now be compared with interferon-alpha monotherapy in randomised controlled trials.

AB - BACKGROUND: Metastatic renal carcinoma has a 2-year survival of around 20% and is largely resistant to chemotherapy. The use of interferons in the treatment of metastatic renal carcinoma remains controversial. Although non-randomised studies suggest that biological therapy with interferons produces a small number of tumour responses, most clinicians judge such treatment to be ineffective. We have investigated the effect of treatment with interferon-alpha on survival in patients with metastatic renal carcinoma.METHODS: In a multicentre, randomised trial, patients with metastatic renal carcinoma were randomly assigned subcutaneous interferon-alpha (three doses--5 MU, 5 MU, 10 MU--for the first week, then 10 MU three times per week for a further 11 weeks; n=174) or oral medroxyprogesterone acetate (MPA; 300 mg once daily for 12 weeks; n=176). The primary endpoint was overall survival. Analysis was by intention to treat. The trial used a triangular sequential design for early termination as soon as results were conclusive. The trial was stopped in November, 1997, when data were available for 335 patients (167 interferon-alpha, 168 MPA).FINDINGS: A total of 111 patients have died in the interferon-alpha group, and 125 patients have died in the MPA group. There was a 28% reduction in the risk of death in the interferon-alpha group (hazard ratio 0.72 [95% CI 0.55-0.94], p=0.017). Interferon-alpha gave an improvement in 1-year survival of 12% (MPA 31% survival, interferon-alpha 43%), and an improvement in median survival of 2.5 months (MPA 6 months, interferon-alpha 8.5 months).INTERPRETATION: The benefit of treatment with interferon-alpha should be weighed against the drug's toxic effects. Combination regimens of biological therapy and chemotherapy should now be compared with interferon-alpha monotherapy in randomised controlled trials.

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KW - Carcinoma, Renal Cell/drug therapy

KW - Female

KW - Humans

KW - Interferon-alpha/therapeutic use

KW - Kidney Neoplasms/drug therapy

KW - Male

KW - Medroxyprogesterone Acetate/therapeutic use

KW - Middle Aged

KW - Neoplasm Metastasis

KW - Nephrectomy

KW - Registries

KW - Survival Analysis

KW - United Kingdom

U2 - 10.1016/S0140-6736(98)03544-2

DO - 10.1016/S0140-6736(98)03544-2

M3 - Article

VL - 353

SP - 14

EP - 17

JO - The Lancet

JF - The Lancet

SN - 0140-6736

IS - 9146

ER -