The present investigations have compared the effect of systemic to local administration of various nonspecific immunostimulating agents (NSSA's), with and without chemotherapy, on the growth of a primary tumor and have evaluated the relative effectiveness of the systemic and local use of those agents combined with chemotherapy on the growth of a distant tumor focus. The intratumor (i.t.) inoculation of Corynebacterium parvum more effectively inhibited primary tumor growth than did its use by any other route tested. Neither Bacillus Calmette-Guérin nor Bru-Pel displayed such a property when administered either i.t. or systemically. Strikingly better results were obtained when i.t. C. parvum or Bru-Pel were given with cyclophosphamide (CY) than did their systemic use either alone or following chemotherapy. This occurred to a lesser degree with Glucan. i.t. C. parvum used in conjunction with CY was more effective than any of the other immunomodulators similarly used. Such findings are analogous to those obtained with systemic NSSA administration. Since the combination of i.t. C. parvum with systemic CY was highly effective in controlling the growth of a distant tumor focus of lesser size than the treated primary tumor, there is justification for further evaluation of the worth of treatment of a primary tumor with NSSA prior to its removal for the control of the metastatic disease.
Other findings in these investigations, worthy of comment, are those indicating (a) that despite the putative uniformity of animals, tumors, and treatment regiments, in any group of mice, there was a wide range of response of individual tumors to the therapy; (b) that regrowth of totally regressed tumors occasionally occurred during continued and prolonged immunochemotherapy; and (c) that administration of certain NSSA's resulted in death when inoculated i.t., but the mortality could be prevented by a dose of CY given 4 days prior to the NSSA.
Supported by USPHS Contract NO1-CB-64044 and Grants CA-14972 and CA-12102 and by funds contributed by Joseph M. Katz, Pittsburgh, Pa. This is Part VI in a series of further observations on the inhibition of tumor growth by Corynebacterium parvum with cyclophosphamide.