Therapeutic effect of an aromatic retinoic acid analog on rats with bladder carcinoma upon administration alone or in combination with mitomycin C.

An aromatic retinoic acid analog (Ro 10-9359) was given orally in combination with intraperitoneal administration of mitomycin C (MMC), in an attempt to reduce the toxicity and enhance the therapeutic effect. Male ACI/N rats were inoculated subcutaneously with BC50-TC cells, an established bladder carcinoma cell line of ACI/N rats. The chemotherapy was initiated at 16 days after the inoculation and continued for 4 weeks thereafter. Tumor growth was significantly inhibited in the rats given 100 mg/kg/week Ro 10-9359 or 0.3 mg/kg/twice a week MMC. Neither additive nor synergistic effect was apparent when these two drugs were given simultaneously. No effect was seen when 0.1 mg/kg/twice a week MMC was given alone or in combination with Ro 10-9359. MMC may suppress Ro 10-9359 activity directly or indirectly by affecting the responding cells. Therefore care should be taken when prescribing retinoids with MMC or possibly with other cytotoxic agents.