Enhancement of antileukemic effect in combination of 5-fluorouracil and OK-432.

OK-432, a streptococcal preparation with potent antitumor activity, has been evaluated for its efficacy in experimental and clincal trials. This preparation, however, was ineffective against mouse L1210 leukemia in all treatment schedules. The results of this study indicate that treatments with OK-432 and nucleic acid antimetabolites, such as 5-fluorouracil (5-FU), exert a synergistic effect against L1210 leukemia probably in conjunction with the immunologic defenses of the host. This therapeutic synergism was to some extent dependent on the dose level of 5-FU and was not produced against the 5-FU-resistant L1210 subline. In mice pre-treated with OK-432 prior to the leukemia implantation, there was no synergistic effect as a result of post-treatment with 5-FU. When BDF mice had previously received X-ray irradiation or administration of corticosteroids, the synergism could not be expected either. Comparative combination therapy with BCG or group C streptococcus resulted in failure to produce therapeutic synergism in this system.