The possibility of integrating adriamycin (Adria) in combined chemoimmunotherapeutic treatments with non-specific immunomodulators was investigated. With an appropriate choice of treatment conditions clear synergistic effects were observed in the L1210 Ha leukemia when Adria was followed by treatment with Corynebacterium parvum (C. parvum), BCG and levamisole; however the Adria-C. parvum combination was found to be the most active. C. parvum appeared additionally to exert better antitumoral activity in this system when associated with Adria than with other antitumorals given in equiactive doses. The high therapeutic activity of the Adria-C. parvum combination was confirmed in three other leukemia systems (P388, LSTRA, L1210 Cr) even in conditions where chemotherapy with Adria alone was ineffective. Clear beneficial effects were additionally seen with this combination in the solid spontaneously metastatizing Lewis lung carcinoma, a system in which the triple therapeutic approach surgery-Adria-C. parvum was more effective than either of the binary combinations. The potential clinical implications of these results and the possible mechanisms at the basis of the synergism between Adria and C. parvum are discussed.
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