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Changes in Growth Rate of an Experimental Solid Tumor Following Increasing Doses of Cyclophosphamide¹

Division of Radiobiology and Biophysics, University of Virginia School of Medicine, Charlottesville, Virginia 22908

Well-defined times for minimum and maximum growth rates of rat hepatoma 3924A were found when cyclophosphamide doses were increased from 50 to 250 mg/kg. Minimum growth rates occurred 8 to 10 days after treatment and maximum growth rates occurred 13 to 16 days after treatment in 5 groups of 10 animals each that received 50, 100, 150, 200, and 250 mg of cyclophosphamide per kg. Tumor growth delay increased from 6 to 18 days when the dose was increased from 50 to 250 mg/kg. The accelerated growth rate of treated tumors on Day 14 after cyclophosphamide (150 mg/kg) was more than twice that of controls on the same day, 0.349 ± 0.030 (S.E.) (day^-1) and 0.156 ± 0.011 (day^-1), respectively. In addition, the accelerated growth rate of treated tumors on Day 14 was greater than that of controls at initiation of treatment, 0.298 ± 0.026 (day^-1) on Day 2. Increased DNA synthetic rate precedes increased tumor cell proliferation, which, in turn, increases tumor volume. Thus, biochemical studies demonstrating increased cellular proliferation confirm accelerated tumor growth following treatment.

¹ Supported in part by a USPHS Research Emphasis Grant (CREG) CA20516 on Experimental Combined Modality (Radiotherapy-Chemotherapy) Studies (ECMRC) from the National Cancer Institute. This is Paper 18 in a series entitled, "Solid Tumor Models for the Assessment of Different Treatment Modalities."

² To whom requests for reprints should be addressed, at Box 392, University of Virginia Hospital, Charlottesville, Va. 22908.

Received 10/23/79. Accepted 3/24/80.