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Antitumor Activity of Interleukin-1 and Cisplatin in a Murine Model System

Jennifer Rubin Grandis, MD; Ming-Jei Chang, MD; Wei-Dong Yu, MD; Candace S. Johnson, PhD

Arch Otolaryngol Head Neck Surg. 1995;121(2):197-200.

Abstract
Background
Interleukin-1 (IL-1) 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 induced acute hemorrhagic necrosis and increased clonogenic cell kill.

Objective
To determine the efficacy of cisplatin and IL-l, 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 14 days after subcutaneous tumor implantation and were monitored for delayed tumor regrowth.

Results
Cisplatin alone, but not IL-1 induced significant delayed tumor regrowth when compared with control. The combination of IL-1 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 compared with those treated with IL-1 alone.

Conclusions
Results of interleukin-1 and cisplatin dose-response experiments reveal that the combination of low-dose cisplatin and interleukin-1 is more effective than high-dose cisplatin alone. Our data suggest that cisplatin and IL-1 may be efficacious in the treatment of SCCHN.

(Arch Otolaryngol Head Neck Surg. 1995;121:197-200)

Author Affiliations
From the Department of Otolaryngology, University of Pittsburgh (Pa) School of Medicine and the Pittsburgh Cancer Institute.

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