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Predictive Values of the in Vivo Diffusion Chamber for Cyclophosphamide Treatment of L1210 Murine Leukemia¹

The Oncology Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205

In vivo culture of tumor cells using the Millipore diffusion chamber implanted i.p. into female C57BL x DBA/2 F₁ (hereafter called BD2F₁) mice provides a means for direct examination of drug effect on tumor cells. The effect of various doses and schedules of i.p. cyclophosphamide (CY) on murine L1210 leukemia cell count in the chambers was compared to survival of leukemia-bearing animals treated similarly. Tumor cell viability was assessed by transfer of chamber contents to recipient animals who were then observed for survival. Unless perturbed by CY, L1210 cells grew in log phase within chambers to 10⁸ cells/cu mm. The effect of CY on chamber cell count was dose related, quantifiable, reproducible, and predictive of survival of leukemia-bearing animals treated similarly. Single doses proved to be more effective than were equally divided doses in decreasing chamber cell number and prolonging leukemic animal survival. Reinjection of L1210 cells rescued from chambers after hosts had been treated with CY revealed that many could not produce tumors. Results suggest that this technique provides reproducible information on drug effects and may be a valuable tool for designing clinically useful dose schedules.

¹ This work was supported in part by USPHS Grant CA 06973 from the National Cancer Institute and General Research Support Grant RR 5378-14.

² Present address: Division of Tumor Immunology, Dana Farber Cancer Institute, 44 Binney Street, Boston, Mass. 02115. To whom requests for reprints should be addressed at The Johns Hopkins Oncology Center, Room 2-109A, Baltimore, Md. 21205.

Received 3/ 5/80. Accepted 1/21/83.