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

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(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.