A quantitative model for the study of the growth and treatment of a tumor and its metastases with correlation between proliferative state and sensitivity to cyclophosphamide.

An experimental tumor model system has been designed to permit quantitative study of the growth of a solid tumor and its métastasesand quantitative study of the response of this tumor and its métastasesto chemotherapy. The Lewis lung carcinoma was transplanted i.m., and tumor growth was followed by serial diameter measurements; these data were then converted to tumor weight by means of a determined conversion equation. The total number of metastatic tumor cells in lung was determined by a quantitative transplant bioassay which involved comparison of tumor growth in bioassay recipients with tumor growth in a series of bioassay standards that had received graded doses of tumor cells under similar transplant conditions. This model was used to study the influence of tumor growth rate and location on sensitivity to cyclophosphamide. The most rapidly growing tumor cells were most sensitive to cyclophosphamide, and the slowly growing tumor cells were least sensitive. A direct correlation was observed between tumor-doubling time and sensitivity to cyclophosphamide. When sensitivity was correlated with differences in tumor growth rate, there were only minor differences in sensitivity related to tumor location. Treatment of early tumors produced a dose-related increase in survival, but treatment of late tumors often shortened survival, especially at the highest doses tested. This evidence of increased toxicity for late treatment, together with the decreased tumor sensitivity with late treatment, may serve as a model for increased interest in chemotherapy of early cancer.