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

(1)基础研究：从2种头颈癌细胞系（KB细胞HEp-2细胞）中建立了顺铂（CDDP）、5-氟尿嘧啶（5-FU）、氨甲喋呤（MTX）和博莱霉素（BLM）耐药细胞系。通过体外生长抑制试验和集落形成试验检测细胞对药物的敏感性。此外，仅使用移植到裸鼠的CDDP抗性细胞系在体内证实了这些结果。结果表明：（1）CDDP耐药细胞系对MTX、BLM、丝裂霉素C（MMC）、培洛霉素（PEP）具有交叉耐药，对5-FU、长春新碱（VCR）、阿霉素（ADM）无交叉耐药;将KB细胞的CDDP抗性细胞系移植到裸鼠体内。这些肿瘤对顺铂耐药，对MTX和ADM不敏感，但对5-FU不耐。（2）5-FU耐药细胞系对CDDP、MTX、PEP、VCR有交叉耐药，对BLM、MMC、ADM无交叉耐药;（3）MTX耐药细胞系对BLM、VCR、PEP有交叉耐药，对CDDP、5-FU、MMC、ADM无交叉耐药;（4）BLM耐药细胞系对CDDP、PEP有交叉耐药，对5-FU、MTX、MMC、VCR无交叉耐药，的ADM。(2)临床研究：采用VMP方案（长春地辛、MTX-甲酰四氢叶酸、PEP）与CF方案（顺铂、5-FU）组成的无交叉耐药序贯化疗方案治疗6例复发性头颈部恶性肿瘤。完全缓解1例，部分缓解2例，有效率50%。完全缓解率为17%。毒性反应包括骨髓毒性、肾毒性、口腔炎、恶心呕吐等，但大多数病例可耐受。需要进一步研究。

(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.