ＣＤＤＰ・５‐ＦＵ・ＩＦＮ‐γ 併用療法の実験的研究

Abstract

Basic studies were conducted on the effect of combined cisplatin (CDDP) and 5-fluorouracil (5-FU). Then the effect of interferon-γ (IFN-γ) added to the combination was investigated.First, three human head and neck carcinomas (2 maxillary sinu s cancers: MC-1, MC-3; 1 mesopharyngeal cancer: MPG-1) transplanted to nude mice were used for experimental chemotherapy. For single drug therapy, the 1/3 LD50 (CDDP 5.9mg/kg or 5-FU 80mg/kg) was administered intraperitoneally three times every four days. For combination therapy, the 1/3 LD50×0.6 of each drug was administered in the same way.IFN-γ (4.0×106U/kg as a single dose; 2.4×106U/kg in combination) was administered intraperitoneally and intratumorally. The results were evaluated by the Battle Columbus Laboratories method.Next, the combined effects of CDDP, 5-FU and IFN-γ were investigated by a human tumor clonogenic assay technique which was a modification of the method by Hamburger and Salmon. A maxillary sinus carcinoma cell line (MMSI-1) was used as the experimental tumor. The tumor cells were exposed to the following concentrations of anticancer drugs: CDDP, 0.02μg/ml; 5-FU, 1μg/ml; IFN-γ, 102U/ml, 103U/ml, 104U/ml.1. The combination of CDDP and 5-FU intraperitoneally had a subadditive effect on MG-1 and MPG-1, but an interferential effect on MC-3.2. Intratumoral IFN-γ administration had a synergistic effect on MC-3 when combined with CDDP and 5-FU.3. Both the combination of CDDP and IFN-γ (104U/ml) and the combination of 5-FU and IFN-γ (104U/ml) had synergistic effects on MMSI-1.4. Strong inhibition (92%) of colony formation of MMSI-1 was observed with the combination of CDDP, 5-FU and IFN-γ (104/ml).