[Combination chemotherapy with 3 or 4 drugs on human breast and gastrointestinal cancer xenografts in nude mice (II)].

Because of the limited effects of single-agent chemotherapy for solid tumors, combination therapy was employed in an attempt to enhance the clinical effects. Following our former report in which the combination effects of mitomycin C (MMC) and 5'-deoxy-5-fluorouridine (5'-DFUR) were clarified, combined applications of 4 drugs, vindesine (VDS), methotrexate (MTX), cisplatin (CDDP) and 5'-DFUR against 3 lines of human breast cancer (H-62, H-31, H-71), and one line each of gastric cancer (H-55) and colon cancer (H-110) xenografted into nude mice were evaluated in comparison with CAF (cyclophosphamide, adriamycin and 5-FU) therapy which is commonly used for breast cancer. Treatment was initiated in groups of 7 mice each when the mean tumor volume of subcutaneous tumors had reached about 100mm3, and the therapeutic effect was evaluated in terms of the inhibition rate (I.R.). A synergistic effect is said to exist when the combination therapy is superior to each single drug therapy at the maximal tolerated dose. Combination therapy with 3 drugs (VDS, CDDP and 5'-DFUR) or 4 drugs (VDS, CDDP, MTX and 5'-DFUR) achieved an I.R. of over 98%, i.e., a marked effect with tumor shrinkage, in 3 lines of tumors (H-55, H-31 and H-62). Moreover, remarkable effects were shown even in the other 2 lines which were insensitive to every single-agent therapy, the I.R. values being 85.7% (H-71) and 78.5% (H-110). A synergistic effect was obtained in 3 of the 5 lines examined. These combination therapies were histologically superior to therapies employing each single-drug therapy or CAF therapy. The side effects for combination of these 3 or 4 drugs evaluated by body weight loss were transient and equivalent to maximal dose of VDS or CDDP. Clinically, it is thought that these combined therapies of 3 or 4 drugs will bring about a considerable response in practice.