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Studies on Development of Non-Cross Resistant Chemotherapy for Head and Neck Cancer

头颈癌非交叉耐药化疗药物开发研究

基本信息

批准号：
01570961
负责人：
INUYAMA Yukio
金额：
$ 1.34万
依托单位：
Hokkaide University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1989
资助国家：
日本
起止时间：
1989 至 1990
项目状态：
已结题

项目摘要

(1) Basic research : Cell lines resistant to cisplatin (CDDP), 5-fluorouracil (5-FU), methotrexate (MTX) and bleomycin (BLM) were established from 2 kinds of head and neck cancer cell lines (KB cell HEp-2 cell). Drug sensitivity to these cell lines was examined in vitro by growth inhibition test and colony formation. Furthermore, these results were confirmed in vivo using only CDDP-resistant cell lines which were transplanted to nude mice. The results obtained were as follows : (1) CDDP-resistant cell lines were cross-resistant to MTX, BLM, mitomycin C(MMC), and peplomycin (PEP), but not so resistant to 5-FU, vincristine (VCR), and adriamycin (ADM). CDDP-resistant cell lines from KB cell were transplanted to nude mice. These tumors were quite resistant to CDDP, and less sensitive to MTX and ADM, but not resistant to 5-FU. (2)5-FU-resistant cell lines were cross-resistant to CDDP, MTX, PEP, and VCR, but not so resistant to BLM, MMC, and ADM (3) MTX-resistant cell lines were cross-resistant to BLM, VCR, and PEP, but not so resistant to CDDP, 5-FU, MMC, and ADM. (4) BLM-resistant cell lines were cross-resistant to CDDP and PEP, but not so resistant to 5-FU, MTX, MMC, VCR, and ADM.(2) Clinical research : Six patients with recurrent head and neck cancer were treated with non-cross resistant sequential chemotherapy which consist of VMP therapy (vindesine, MTX-Leucovorin, PEP) and CF therapy (CDDP, 5-FU). Complete response was achieved in 1 and partial response in 2 out of the 6 patients with a response rate of 50%. The complete response rate was 17%. Toxic effects include bone marrow toxicity, nephrotoxicity, stomatitis, nausea and vomiting, but these toxicities were tolerable in most cases. Further studies were warranted.

(1)基础研究：从2种头颈部肿瘤细胞系（KB细胞HEp-2细胞）中建立顺铂（CDDP）、5-氟尿嘧啶（5-FU）、甲氨蝶呤（MTX）和博来霉素（BLM）耐药细胞系。通过生长抑制试验和菌落形成检测对这些细胞系的药物敏感性。此外，仅用裸鼠移植的抗cddp细胞系在体内证实了这些结果。结果表明：(1)cddp耐药细胞株对MTX、BLM、丝裂霉素C（MMC）、培霉素（PEP）有交叉耐药，对5-FU、长春新碱（VCR）、阿霉素（ADM）无交叉耐药。将KB细胞的抗cddp细胞株移植到裸鼠体内。这些肿瘤对CDDP有较强的耐药性，对MTX和ADM的敏感性较低，但对5-FU无耐药性。(2)5-FU耐药细胞株对CDDP、MTX、PEP和VCR交叉耐药，对BLM、MMC和ADM不耐药；(3)MTX耐药细胞株对BLM、VCR和PEP交叉耐药，对CDDP、5-FU、MMC和ADM不耐药；(4)BLM耐药细胞株对CDDP和PEP交叉耐药，对5-FU、MTX、MMC、VCR和ADM不耐药。(2)临床研究：对6例复发性头颈癌患者进行无交叉耐药序贯化疗，由VMP治疗（长春地西、mtx -亚叶酸素、PEP）和CF治疗（CDDP、5-FU）组成。6例患者中1例达到完全缓解，2例达到部分缓解，缓解率为50%。完全有效率为17%。毒性作用包括骨髓毒性、肾毒性、口炎、恶心和呕吐，但这些毒性在大多数情况下是可耐受的。进一步的研究是必要的。