This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by DeWys, W. D. Search for Related Content PubMed PubMed Citation Articles by DeWys, W. D.

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 Cyclophosphamide¹

Department of Medicine, Division of Oncology, University of Rochester School of Medicine and Dentistry, Strong Memorial Hospital, and Rochester General Hospital, Rochester, New York 14642

An experimental tumor model system has been designed to permit quantitative study of the growth of a solid tumor and its metastases and quantitative study of the response of this tumor and its metastases to 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.

¹ Supported in part by Contract PH 43-64-91 from the Cancer Chemotherapy National Service Center, National Cancer Institute, and Grants CA-08112 and CA 11083-02, National Cancer Institute. A preliminary report of this work has been presented (7).

² Advanced Clinical Fellow of the American Cancer Society to whom reprint requests should be addressed at the Department of Medicine, University of Rochester School of Medicine and Dentistry, Rochester, N. Y. 14642.

Received 6/10/71. Accepted 11/ 4/71.

This article has been cited by other articles:

				F. Di Nicolantonio, L. A. Knight, P. A. Whitehouse, S. J. Mercer, S. Sharma, P. A. Charlton, D. Norris, and I. A. Cree The ex vivo characterization of XR5944 (MLN944) against a panel of human clinical tumor samples Mol. Cancer Ther., December 1, 2004; 3(12): 1631 - 1637. [Abstract] [Full Text] [PDF]