Eradication of palpable intradermal murine bladder tumors by systemic interleukin-2 and cyclophosphamide in C3H mice.
The effect of cyclophosphamide on interleukin-2 (IL-2) therapy was investigated using the intradermal MBT-2 tumor in C3H mice. Human recombinant IL-2 (Biogen) was given intraperitoneally at doses ranging from 5,000 to 30,000 U, three times a day for 5 or 11-13 consecutive days beginning on day 10 after tumor implantation. When IL 2 was given alone, mice could not tolerate greater than 5 days of 5,000 U IL 2/injection: Administration of 10,000 and 15,000 U/injection of IL-2 for 5 days resulted in 64% (9 of 14) and 100% (14 of 14) mortality, respectively. Chemotherapeutic agents (cisplatin at 6 mg/kg or JM-8 75 mg/kg) and daily administration of cortisone acetate (75 mg/kg) partially protected mice from IL-2-induced toxic deaths. Coadministration of mannitol showed no protective effect. The combination of IL-2 and CY at 75 or 100 mg/kg, however, dramatically reduced the mortality induced by IL-2 and made it possible to escalate the dose and long-term administration of IL-2. Combination administration of 75 mg/kg CY with 15,000 U/injection of IL-2 for 11-13 days caused tumor regressions and resulted in a 66% (8 of 12) cure rate.
Lee
K
K
Department of Urology, University of Rochester School of Medicine, NY 14642.
O'Donnell
R W
RW
Marquis
D
D
Cockett
A T
AT
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D016190:Carboplatin; D002277:Carcinoma / Q000139:chemically induced / Q000628:therapy*; D002945:Cisplatin / Q000627:therapeutic use; D003520:Cyclophosphamide / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D007274:Injections, Intraperitoneal; D007279:Injections, Subcutaneous; D007376:Interleukin-2 / Q000627:therapeutic use*; D051379:Mice; D008815:Mice, Inbred Strains; D009368:Neoplasm Transplantation; D009944:Organoplatinum Compounds / Q000627:therapeutic use; D001749:Urinary Bladder Neoplasms / Q000139:chemically induced / Q000628:therapy*
D000970:Antineoplastic Agents; D007376:Interleukin-2; D009944:Organoplatinum Compounds; D003520:Cyclophosphamide; D016190:Carboplatin; D002945:Cisplatin