|N. Wolmark, MD, University of Pittsburgh, Penn and coinvestigators found added alpha interferon (INF) did not improve the efficacy of 5-fluorouracil (5-FU)/leucovorin (LV). This well-controlled clinical trial included over 2000 advanced CRC patients. INF increased toxicity and decreased compliance with 5-FU/FV therapy. Survival curves at 4 years' follow-up were virtually identical. The results require reexamination of the rationale for adding INF to 5-FU reginens.|
|Rationale for megatrial||INF significantly decreased the breakdown of 5-FU in blood mononuclear
cells of patients with gastrointestinal (GI) adenocarcinoma (J Natl
Cancer Inst 1992;84:1820). A pilot study in 31 patients with metastatic
GI adenocarcinoma showed comedication with INF increased 5-FU toxicity
and decreased 5-FU clearance. Reported toxicity included mucositis,
diarrhea and thrombocytopenia (J Clin Oncol 1991;9:1811).
Comparative Phase II studies, published during 1989-1991, did not give a definitive answer on the contribution of IFN in patients treated with 5-FU for advanced CRC (J Clin Oncol 1989;7:1769; Cancer 1990;66:2470; and J Clin Oncol 1991;9:1806). Prolonged overall and disease-free survival by 5-FU/LV treatment of CRC, reported in Clin Oncol 1993;11: 1879, prompted evaluation of added INF as a means of increasing efficacy.
|Study CO5 protocol||Patients with Dukes' B and C carcinoma of the colon entered to receive
5-FU/FV alone (control) or with added INF (test). Both arms consisted of
six 28-day cycles:
|Results on 2129 evaluable patients||
Wolmark reported nearly identical distributions in both groups for age,
gender, Dukes' classification, and treatment-related deaths. Survival
curves for both arms were virtually superimposable covering 4 years'
follow-up. Overall and disease-free survival rates were:
|Remarks of invited discussant||C. Erlichman, MD, Mayo Clinic, Rochester, Minn, found the negative results answered the original question: Does INF add anything to 5-FU/LV efficacy in CRC? The Phase III protocol did not require dose adjustment of 5-FU in the control arm because of drug toxicity from accumulation. More research is needed to evaluate modulation of 5-FU catabolism by INF as a method for increasing efficacy.|
Presented at the American Society of Clinical Oncology (ASCO) Meeting,
May 16-19, 1998
Copyright © 1998 Conrad Group Inc. All Rights Reserved
Eugene A. Conrad, PhD, MPH / ISSN 1078-2230 / June 1998
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