[Effects of HCFU and TNP 470 on liver metastasis of BALB/c retroperitoneal sarcoma (LMFS)]

Combination therapy using HCFU and TNP 470, which inhibits angiogenesis, was examined for effectiveness against the footpad injection model of LMFS tumor. This LMFS, a retroperitoneal sarcoma of BALB/c mice, proliferated at the inoculation site (100% take) and all mice operated on after day 15 had spontaneous metastatic nodules in the liver. Mice with the LMFS tumor were given HCFU and 5-FU (5 days/week), and/or TNP 470 (3 days/week) from day 3 for 3 weeks and sacrified at day 28 under anesthesia. Seven of 10 mice receiving 5-FU and TNP 470 died from the side effects of the drugs. Mean tumor weight and liver metastatic nodules were determined and compared with a control group. The results were as follows: HCFU group: 94.6%, 11.8%, 5 FU group: 73.9%, 28.8%, TNP 470 group: 67.6%, 44%, HCFU and TNP 470 group: 33.3%, 6.4%. Mice with LMFS were given HCFU and/or TNP 470 from day 3 for 4 weeks. The foot on the injected side was amputated on day 15, and the animals were sacrified on day 35. Liver metastatic nodules compared with those of the operation (OP) group as follows: OP + HCFU group: 14.4%, OP + TNP group: 39.1%, and OP + HCFU + TNP 470 group: 5.4%. Histologically, 5 of 5 mice of the OP group, 3 of 5 of the OP + HCFU group, 4 of 5 of the OP + TNP 470 group and 1 of 5 of the OP + HCFU + TNP 470 group had liver metastases. These results show that while either HCFU or TNP 470 is effective by itself, a combination of these drugs is more effective against liver metastasis.