Comparative responsiveness and pharmacokinetics of doxorubicin in human tumor xenografts

Abstract

The antineoplastic activity of the anthracyclin antibiotic doxorubicin (Adriamycin®) differs in its cytotoxic effectiveness against different types of human tumors. In the present study the effect of doxorubicin on the growth of two human lung carcinomas and one human mammary carcinoma transplanted into athymic mice was correlated with the pharmacokinetics of doxorubicin in the same tumors after intraperitoneal administration. Doxorubicin produced a greater inhibition of tumor growth in the lung carcinomas than in the mammary carcinoma. Furthermore, the pharmacokinetic characteristics of doxorubicin differed widely within the three human solid tumors. No apparent correlation was found to exist between the different tumor growth sensitivities to doxorubicin and the pharmacokinetic parameters of doxorubicin within the tumor tissue. It is suggested that the differences in the demontrated antitumor effectiveness of doxorubicin may be due to differences in the “intrinsic sensitivity” of the three human solid tumors.