MAGUCHI Shiro Hokkaido University Medical Hospital, Instructor, 医学部附属病院, 助手 (20199665)
TANAKA Kazuhito School of Medicine, Keio University, Instructor, 医学部, 助手 (30179741)
ISHIKAWA Kazuo Hokkaido University School of Medicine, Instructor, 医学部, 助手 (80212835)
SATOH Masaki Hokkaido University Medical Hospital, Instructor, 医学部附属病院, 助手 (20215841)
|Budget Amount *help
¥2,100,000 (Direct Cost : ¥2,100,000)
Fiscal Year 1990 : ¥500,000 (Direct Cost : ¥500,000)
Fiscal Year 1989 : ¥1,600,000 (Direct Cost : ¥1,600,000)
(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.