Multifactorial analysis of parameters influencing chemosensitivity of human cancer xenografts in nude mice

The results of single-agent chemotherapy, with 11 anti-cancer agents, of 15 human gastro-intestinal and breast cancer lines xenografted into nude mice indicate inherent individuality of chemosensitivity spectrum of each tumor. The following 9 parameters have been measured as factors possibly relevant to chemosensitivity of tumor tissue or tumor-bearing mice: grade of histological differentiation, vascularity, percentage of necrosis, VDT, 3H-thymidine LI, human LDH activity in the cancer tissue, tissue/serum LDH ratio, TdR Pase activity, and serum CEA. These parameters exhibited presumably constant values for each tumor line. Chemosensitivity, i.e., inhibition of tumor growth by a given drug, was used as the dependent variable, and values of the 9 parameters in each cancer as the explanatory variables. Multiple regression analyses with stepwise deletion were performed for each of the 11 drugs. The equations for 8 drugs exhibited coefficients of determination of over 70%, and in particular those for M-83 (a derivative of mitomycin C), nimustine hydrochloride and doxorubicin exceeded 80% by equations with 3–4 parameters. Consequently, the estimated value for each line of effectiveness derived from the equations for these 8 drugs showed remarkable coincidences with the actual values for the inhibition rates of the corresponding drugs.