Lack of synergy between 5-fluorouracil and interferon-gamma in the treatment of malignancy in the rat.
Numerous in vivo studies have reported synergism between 5-fluorouracil (5-FU) and interferon-gamma (IFN-gamma) but this has not been the case in clinical trials. As the immunomodulatory effects of IFN may be of greater importance in vivo than its direct anti-proliferative activities, it was of interest to determine whether the myelosuppressive effects of high dose 5-FU were responsible for the lack of enhanced activity of the combined drug treatment in the clinical setting. Using an animal model, the anti-tumour activity of three doses of 5-FU (5, 10 and 20 mg/kg/day, continuous intravenous infusion of 7 days) and concurrent IFN-gamma (5 x 10(5) U/kg/day, bolus IV for 5 days) were compared to 5-FU alone. IFN-gamma treatment alone produced a significant anti-tumour response relative to control. No synergism was observed at any dose of 5-FU when combined with IFN-gamma treatment despite white blood cell counts being similar to that in the IFN-gamma group at the lowest dose of 5-FU treatment. Thus, a lack of synergism in vivo is unlikely to be due to myelosuppression resulting in diminished immune response. However, other factors such as tumour type, size and location may be important in determining the final outcome.
Codde
J P
JP
University Department of Surgery, Royal Perth Hospital, The Netherlands.
Vines
J A
JA
van der Meide
P H
PH
Burton
M A
MA
Gray
B N
BN
D000818:Animals; D001853:Bone Marrow / Q000187:drug effects*; D004347:Drug Interactions / Q000502:physiology*; D005472:Fluorouracil / Q000494:pharmacology*; D007371:Interferon-gamma / Q000494:pharmacology*; D007958:Leukocyte Count; D008297:Male; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000473:pathology; D010976:Platelet Count; D051381:Rats; D011919:Rats, Inbred Strains
D007371:Interferon-gamma; D005472:Fluorouracil