EORTC (30885) randomised phase III study with recombinant interferon alpha and recombinant interferon alpha and gamma in patients with advanced renal cell carcinoma

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.

Phase II Study with Interferon alpha-2a and 13-cis-Retinoic Acid in Patients with Metastatic Renal Cell Carcinoma. A Trial of the Phase II Study Group of the Association for Medical Oncology of the German Cancer Society

“…The regimen of IF-alpha-2a and retinoic acid used in this study showed poor antitumor activity with only an 8% objective response rate. In several studies using interferon therapy for the treatment of RCC, response rates varying from 5 to 25% were reported [14,15]. The present study was planned as a confirmative study because the orginal data of the first phase II study with the drug combination mentioned above had shown impressive anticancer activity [7] with an objective response rate of 30% and the observation of durable responses, suggesting that a synergistic effect of the addition of RA to IF was responsible for the augmented antitumor activity.…”

Successful Treatment With Novel Triple Drug Combination Consisting of Interferon-γ, Interferon Alfacon-1, and Ribavirin in a Nonresponder HCV Patient to Pegylated Interferon Therapy

“…No significant, unexpected adverse events were noted; there was an acceptable safety and tolerability profile in this group of patients. Beside hepatitis B, the experience with combination therapy with interferon-α and interferon-γ is in oncologic conditions, where significant, unexpected toxicities have not been seen (10)(11)(12)(13)(14).…”

Resection of a Solitary Pancreatic Metastasis from Renal Cell Carcinoma with a Gallbladder Carcinoma: Report of a Case

“…Immunotherapy with interferon has shown promising results in some studies but not in others, with effectiveness ranging from 0% to 31%, so the efficacy of this therapy remains controversial. 10,13,16 Advanced GBC has a poor prognosis and requires extensive surgical treatment such as hepatic resection and lymph node dissection. For our patient, who had GBC with regional lymph node spread, we expected that curative radical surgery could improve the chance of long-term survival.…”