Effect of 4'-doxorubicin analogs on heterotransplantation of human tumors in congenitally athymic mice.

The antitumor activity of three new doxorubicin (DX) derivatives with less cardiotoxicity than the parent compound was tested against several human tumors representative of some of the major classes of human cancer. The tested DX derivatives, modified on the 4' position of the amino sugar, were 4'-epiDX, 4'-deoxyDX, and 4'-O-methylDX. Fourteen human tumors (three breast tumors, three lung tumors, three melanomas, two ovarian tumors, one prostate tumor, one sarcoma, and one larynx tumor) serially transplanted in athymic mice were used to screen the antineoplastic activity of the 4'-DX derivatives. BALB/c nude mice were treated iv with equitoxic doses of each as a single agent (less than or equal to LD10) on a weekly basis for 3-4 weeks, starting when the tumor became relatively large. 4'-EpiDX, which has a higher threshold limit of cardiac toxicity in man, was found active against breast, lung (epidermoid and oat cell carcinoma), prostate, and ovarian tumors. This drug showed particularly good activity against melanomas. 4'-DeoxyDX was active against breast and prostate tumors, while 4'-0-methylDX was active against breast and ovarian tumors and possibly sarcoma.