Modification of Anti-cancer Drug Formula and Its Local Administration

目前临床肿瘤化疗的效果并不理想，但对部分泌尿生殖系统和淋巴道肿瘤的治疗效果不佳。如何提高现有抗癌药物的药效一直是最重要的问题之一。从这一点来看，人们已经进行了许多尝试，例如对药物的结构进行修饰，改变给药途径或给药方案，以及开发特定的药物输送系统来改善药物的化疗性能。目前的研究工作旨在开发定时释放系统，为肿瘤部位提供所需时间内足够数量的抗癌药物，并对这些药物进行局部给药。为此，人们开发和研究了脂肪乳剂和MMC-葡聚糖偶联物等结构修饰药物。在用家兔进行的实验研究中，使用油包球型(S/O)乳剂极大地提高了博莱霉素向淋巴结的转移率和从结节的缓释速度--比使用W/O乳剂高两倍多。采用S脂肪乳剂瘤内局部给药治疗34例淋巴管瘤和14例晚期胃肠癌。结果令人满意，表明打赌将比手术治疗淋巴管瘤更有益。研究了高分子量丝裂霉素C前体药物--丝裂霉素C-葡聚糖偶联物(MMC-D)的抗肿瘤活性，与MMC相比，其瘤内注射具有更好的抗肿瘤作用。另一项实验研究表明，MMC-D的抗肿瘤作用是由电荷和分子质量决定的。13例晚期不能手术的胃肠癌患者中，6例(47%)获得了瘤内注射MMC-D的临床疗效。

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.