Response to chemotherapy of human,malignant melanoma xenografts in athymic,nude mice

In attempts to elucidate the factors determining individual differences in response of tumors to chemotherapeutic agents, the sensitivity of six human malignant melanomas growing in athymic, nude mice was studied. Six agents, viz. DTIC, CCNU, vinblastine, procarbazine, as well as the toxic lectins abrin and ricin, were administered in maximum tolerable doses to the tumor-bearing mice. The response to treatment was expressed as tumor growth delay, i.e. the number of volume doubling times saved by the treatment. The xenografts had very nearly retained the morphology of the parent tumors and were histologically similar. They showed different and characteristic early growth rates and also wide variations in their response to the agents tested. Unexpectedly, in the case of DTIC, CCNU and procarbazine, the response of the xenografts proved to be inversely related to the early growth rates of the tumors. For vinblastine, abrin and ricin, no correlation between response and growth rate of the tumors was apparent. Procarbazine had the best overall effect among the agents here tested. DTIC, CCNU and vinblastine had somewhat less and about equal overall efficiency. The plant toxin abrin, which acts by inhibiting protein synthesis, was at least as effective as DTIC. When abrin was given together with DTIC, the effect on the two xenografts tested was superior to that of each agent given alone. The wide variations observed in the response of the histologically similar xenografts to the different agents demonstrate that testing of the chemosensitivity of human xenografts requires the use of a panel of tumors of each histological type. The clear relationship found between the early growth rate of the xenografts and their sensitivity to three of the drugs most commonly used in the treatment of malignant melanomas, may have clinical implications.