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Effects of Combination Drug Therapy on the Subcutaneous and Pulmonary Growth of a Slow and a Fast-growing C3H/He Mammary Carcinoma¹

Department of Cancer Therapy Development, Pondville Hospital, Walpole, Massachusetts 02081 [J. V.] and Department of Medicine, Tufts New England Medical Center, Boston, Massachusetts 02111 [M. E. C.]

Changes in susceptibility to treatment with Cytoxan, methotrexate, 5-fluorouracil, and Adriamycin, single or in combination, have been studied during the initial and progressive stages of s.c. and pulmonary (via tail vein injection) growth of two transplanted syngeneic C3H/He mammary carcinomas. One tumor was fast growing, reaching a size of 3 mm from a 1-mm s.c. implant in 7 days; the second tumor would grow to the same size in 30 days. The tumor with the slower growth rate was more susceptible to drug treatment, manifested by delayed growth as well as by prevented growth. The slower-growing tumor also remained susceptible longer, when treatment was delayed, than did the faster-growing tumor. Pulmonary growth was more often prevented by drug treatment than was s.c. growth. Tumor implants s.c. which had reached palpable size could be reduced temporarily to impalpable size by effective drug treatment but were rarely cured. The importance of early treatment relative to the time of tumor implantation was indicated when early treatment with a single drug proved more effective than did delayed treatment with a more potent combination of drugs.

¹ Supported by Grant CA-15960 awarded by the National Cancer Institute, by Grant NIH-5-S07 RR 05598, and by the Charlton Fund of the Tufts University School of Medicine.

² To whom requests for reprints should be addressed.

³ Present address: Department of Medicine, University of Massachusetts Medical Center, Worcester, Mass. 01605.

Received 3/ 2/79. Accepted 8/ 2/79.