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Antitumor activity of interleukin-1 alpha and cisplatin in a murine model system
J R Grandis1, M J Chang, W D Yu
1Department of Otolaryngology, University of Pittsburgh School of Medicine, Pa.
Background:
Interleukin-1 alpha (IL-1 alpha) has potent antitumor activity either alone or combined with alkylating agents such as cisplatin and mitomycin C or porfiromycin. Cisplatin is an effective chemotherapeutic agent in the treatment of advanced squamous cell carcinoma of the head and neck (SCCHN). In the murine SCCVII/SF squamous cell carcinoma tumor model, IL-1 alpha induced acute hemorrhagic necrosis and increased clonogenic cell kill.
Objective:
To determine the efficacy of cisplatin and IL-1 alpha, singly and in combination, in the treatment of SCCHN.
Methods:
Syngeneic C3H/HeN mice were treated with single-dose, concurrent, intraperitoneal injections of cisplatin and interleukin-1 alpha 14 days after subcutaneous tumor implantation and were monitored for delayed tumor regrowth.
Results:
Cisplatin alone, but not IL-1 alpha, induced significant delayed tumor regrowth when compared with control. The combination of IL-1 alpha and cisplatin was even more effective in delaying tumor regrowth than cisplatin alone. Fractional tumor volume was significantly reduced in animals treated with the combination of cisplatin and IL-1 alpha compared with those treated with IL-1 alpha alone.
Conclusions:
Results of interleukin-1 alpha and cisplatin dose-response experiments reveal that the combination of low-dose cisplatin and interleukin-1 alpha is more effective than high-dose cisplatin alone. Our data suggest that cisplatin and IL-1 alpha may be efficacious in the treatment of SCCHN.