[Effects of alternating chemotherapy with 2 non-cross-resistant drug combinations on human alimentary and breast cancer xenografts in nude mice].

Despite the recent advances made in the development of anticancer drugs, any single chemotherapy treatment has only limited effects on cancers of the stomach, colon and breast, so that the combined use of multiple drugs is necessary for the treatment of solid tumors. In our previous studies with human gastrointestinal and breast cancers xenografted into nude mice, combination therapy with mitomycin C (MMC) and 5'-deoxy-5-fluorouridine (5'-DFUR) [I] or cisplatin (CDDP), vindesine (VDS) and 5'-DFUR [II] produced higher response rates than single-agent therapy with any one of these drugs. In the present study, the effectiveness of alternating chemotherapy with the combination regimens I and II was evaluated using 3 lines of cancer xenografts with special emphasis on relapse-free survival. Even in untreated controls, different influences of these cancers on the host as well as differences in their growth rates resulted in delayed tumor death in breast cancer (H-31) compared with pancreas (H-48) and colon (H-110) cancers. Four cycles of the regimen I drug combination failed to prolong life due to toxic side effects in every cancer line. In H-48 cancer, although regimen I alternated with regimen II achieved an inhibition rate (IR) of 96% with tumor shrinkage, 2 of 7 mice died of toxicity. In H-110 cancer, which is only sensitive to VDS, 4 cycles of regimen II alone produced an IR of 83.5%, which was slightly superior to alternating chemotherapy. In H-31 cancer, which retains considerable sensitivity to CDDP, MMC and 5'-DFUR, mice treated with alternating chemotherapy starting from regimen I for a total of 5 cycles attained a maximal IR of over 99% including disappearance of the tumor in 6 of 7 mice during the treatment course, and at the end of the experiment (20th week), all had survived with one in a relapse-free state, compared with the control group which had only 2 survivors. Thus, cyclic delivery of two non-cross-resistant drug combinations with optimal treatment doses and timing prevented toxic effects and induced long-term survival without relapse. Also, this appears to be the first study that has evaluated the effects of cancer chemotherapy in a human solid tumor-nude mouse system according to survival rate.