Adverse effect of cyclophosphamide at moderate dose in combination with standard drugs on intraperitoneally implanted Lewis lung carcinoma in mice.

Adverse (tumor-enhancing) effects of cyclophosphamide at moderate dose (50 mg/kg) given therapeutically were confirmed on the intraperitoneally implanted Lewis lung carcinoma (LLC) in allogeneic DBA/2 and BALB/c mice. It was recently demonstrated that antitumor effects of five standard drugs (actinomycin D, adriamycin, BCNU, 5-fluorouracil and methotrexate) were abolished or diminished when cyclophosphamide (50 mg/kg) was therapeutically combined with such drugs against intraperitoneally implanted LLC both in syngeneic C56BL/6 and allogeneic DBA/2 and BALB/c mice, while the effects of three drugs (cis-diamminedichloroplatinum, 5-thioguanine and vincristine) were not affected by the cyclophosphamide therapy. It is suggested that cyclophosphamide therapy at adjusted lower doses in man might not only be effective but also have a risk to enhance tumor growth and diminish the beneficial effects of other drugs in combination chemotherapy.