EORTC (30885) randomised phase III study with recombinant interferon alpha and recombinant interferon alpha and gamma in patients with advanced renal cell carcinoma
Faculty of Medicine and Health Sciences
The British journal of cancer. - London
, p. 371-375
University of Antwerp
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 pg 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 mu g 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.