Abstract |
In the treatment of renal cell carcinoma both complete (CRs) and partial remissions (PRs) have been obtained using recombinant (r) interferon alpha (IFN-alpha), with response rates ranging from 0 to 31% (mean 16%). rIFN-gamma is a potent immunostimulating agent, but the clinical experience of its use is limited and results are conflicting. In a phase II study with the combination of rIFN-alpha 2c (Boehringer Ingelheim) and rIFN-gamma (Genentech, supplied by Boehringer Ingelheim) in 31 eligible patients, a response rate of 25% was recorded. Based on this observation a randomised phase III study was initiated to investigate the possible advantage of the addition rIFN-gamma to rIFN-alpha 2c treatment. Treatment consisted of rIFN-alpha 2c 30 micrograms m-2 = 10 x 10(6) IU m-2 s.c. twice weekly in arm A and the same dose of rIFN-alpha combined with rIFN-gamma 100 micrograms m-2 = 2 x 10(6) IU m-2 in arm B. Eligibility criteria included documented progression of disease; patients with bone lesions only and overt central nervous system metastases were excluded. Between November 1988 and September 1990, 102 patients were entered into the study. An interim analysis showed a response in 7/53 (13%) patients (two CRs and five PRs) in the rIFN-alpha 2c monotherapy arm and in 2/45 (4%) (one CR and one PR) patients in the combination arm. This difference was not statistically significant (P = 0.17). The probability of missing an eventual 10% advantage for the combination is 0.001. The numbers are insufficient to rule out a negative effect of the addition of rIFN-gamma. The dose intensity of IFN-alpha 2c for the two treatment arms was the same. The addition of rIFN-gamma does not improve the response rate of rIFN-alpha 2c monotherapy. A possible detrimental effect cannot be excluded.
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Authors | P H De Mulder, G Oosterhof, C Bouffioux, A T van Oosterom, K Vermeylen, R Sylvester |
Journal | British journal of cancer
(Br J Cancer)
Vol. 71
Issue 2
Pg. 371-5
(Feb 1995)
ISSN: 0007-0920 [Print] England |
PMID | 7841054
(Publication Type: Clinical Trial, Clinical Trial, Phase III, Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial)
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Chemical References |
- Immunologic Factors
- Interferon alpha-2
- Interferon-alpha
- Recombinant Proteins
- Interferon-gamma
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Topics |
- Adult
- Aged
- Bone Neoplasms
(mortality, secondary, therapy)
- Carcinoma, Renal Cell
(mortality, pathology, secondary, therapy)
- Drug Synergism
- Female
- Humans
- Immunologic Factors
(administration & dosage, adverse effects, therapeutic use)
- Interferon alpha-2
- Interferon-alpha
(administration & dosage, adverse effects, therapeutic use)
- Interferon-gamma
(administration & dosage, adverse effects, therapeutic use)
- Kidney Neoplasms
(mortality, pathology, therapy)
- Male
- Middle Aged
- Recombinant Proteins
- Survival Rate
- Treatment Outcome
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