Modification of Anti-cancer Drug Formula and Its Local Administration

目前临床肿瘤化疗除针对部分泌尿生殖系统肿瘤和淋巴肿瘤外，效果并不理想。如何提高现有抗癌药物的疗效一直是一个重要的问题。从这个角度来看，为了提高药物的化疗性能，人们进行了许多尝试，如改变药物的结构，改变给药途径或给药方案，以及开发特定的给药系统。目前研究的重点是开发缓释系统，为肿瘤部位提供所需时间内足够量的抗癌药物，以及局部给药。为此，人们开发和研究了脂肪乳剂和mmc -葡聚糖缀合物等结构改性药物。在使用家兔的实验研究中，使用油球型（S/O）乳剂极大地提高了博来霉素进入淋巴结的转移率及其从淋巴结的持续释放率，比使用W/0乳剂高出两倍多。本文对34例淋巴管瘤患者和14例晚期胃肠癌患者采用瘤内脂肪（S/O）乳剂（BET）局部给药治疗。结果令人满意，表明下注比手术治疗淋巴管瘤更有益。对丝裂霉素C高分子量前药MMC-葡聚糖缀合物（MMC- d）的抗肿瘤活性进行了研究，结果表明，与MMC相比，肿瘤内注射MMC-d对实验性肿瘤的作用更明显。另一项实验研究表明，MMC-D的抗肿瘤作用受电荷和分子量的支配。13例晚期不能手术的胃肠癌患者中6例（47%）瘤内注射MMC-D治疗效果良好。

Results of current clinical cancer chemotherapy have been not satisfactory good except for ones against a part of urogenital and lymphatic tumors. It has been one of the most important problems how the effect of anticancer agents currently available can be enhanced. From this view point, numerous attempt such as structural modification of the drug, alteration in route of administration or dose regimen, and development of a specific drug delivery system have been made to improve chemotherapeutic properties of agents. The effort in the current study has been directed towards the development of timed-release systems, which could provide the tumor site with sufficient amount of anticancer agents for required period of time, and towards topical administration of those drugs. The structurally modified drugs such as a fat emulsion and MMC-Dextran conjugate have been developed and studied for this purpose. Tn the experimental study using domestic rabbits the rate of transfer of bleomycin into lymph nodes and of its sustained release from the nodes was extremely enhanced by the use of a sphere-in-oil type (S/O) emulsion -- more than two times higher than in the use of a W/0 emulsion. Clinically, 34 cases with lymphangiomas and 14 cases with advanced gastrointestinal cancers were treated by topical administration of drugs intratumorally in a fat (S/O) emulsion (BET). Results were satisfactory, indicating BETs would be more beneficial than surgical treatments for lymphangiomas. The antitumor activity of a high molecular weight pro-drug of mitomycin C, MMC-dextran conjugate (MMC-D), was examined and its intratumoral injection showed a superior effect on experimental tumors compared with MMC. Another experimental study has demonstrated that the antitumor effect of MMC-D is governed by electric charge and molecular weight. Clinical effects of the treatment by intratumoral injection of MMC-D were found in 6 of 13 patients (47 %) with advanced inoperable gastrointestinal cancer.