Development of resistance to rubidazone (NSC-164011) in Ehrlich ascites tumor in vivo.

Resistance to a new daunorubicin derivative, rubidazone, was developed in a strain of Ehrlich ascites tumor in vivo by treatment with the drug during 11 weekly passages of the tumor. In this tumor reciprocal cross resistance was found between rubidazone, daunorubicin, adriamycin, vincristine, and vinblastine. There was no change in sensitivity of the tumor to methotrexate, 6-mercaptopurine, BCNU, cytosine arabinoside, or actinomycin D. The resistance was stable for at least 71 weeks when treatment was continued and for at least 18 weeks when treatment was discontinued. Rubidazone given intraperitoneally was significantly less toxic than daunorubicin and adriamycin; unlike the findings with daunorubicin and adriamycin, late toxic death (after 30 days) often occurred. In the wild-type tumor the growth inhibition with rubidazone was less than with daunorubicin and adriamycin on an equal weight basis. The LD10 of rubidazone inhibited the growth to nearly the same extent as did the LD10 of daunorubicin and adriamycin.