Adriamycin: an animal model for detection of oncolytic and cardiotoxic activity

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The present studies were designed to investigate the feasibility of utilizing the VX2 carcinoma (CA) in the rabbit as an experimental model to detect therapeutic efficacy and cardiotoxic activity of adriamycin (ADR) and related analogues. 38 NZW rabbits were divided into 3 groups (Gr) of 10, 19, and 9 and treated as follows: Gr I-VX2 CA; Gr II-VX2 CA+ADR; Gr III-ADR. ADR was administered IV for 1-7 treatments at a dose schedule of 35 mg/M2 q 21 days commencing 72 hr post IM innoculation of either VX2 CA cells or saline. All rabbits in Gr I died by day 62 with massive local tumor invasion and metastases to lymph nodes and lungs. ADR treated rabbits in Gr II had a 205% increase in median survival time compared to those in Gr I with one long term survivor in remission. Only 33% had evidence of metastases beyond regional lymph nodes and 50% had histopathologic evidence of cardiomyopathy. Rabbits in Gr III survived longer than those in either Gr I or Gr II, although the majority died eventually of congestive heart failure after receiving total doses of ADR ≥175 mg/M2. The findings of this study indicate that treatment of the VX2 CA in rabbits with ADR results in a significant increase in median survival time, a diminution of disseminated metastases and development of a cardiomyopathy associated with low accumulative doses. It is possible the characteristic hypercalcemia of the VX2 CA potentiates the cardiotoxic activity of ADR.

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Proceedings of the American Association for Cancer Research

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