Chemosensitivity of human head and neck cancer xenografts in the clonogenic assay and in nude mice.
The potential use of human head and neck (H & N) tumours, growing in athymic nude mice, for preclinical assessment of cytostatic drug sensitivity in a soft agar cloning system was examined. Of 20 H & N tumour xenografts, obtained from 6 different xenograft lines, 17 demonstrated sufficient colony growth to evaluate in vitro drug sensitivity. Moreover, all xenografts provided enough cells to test 8 cytostatic drugs at 3 concentrations each. A dose-dependent inhibition of colony growth was obtained with all drugs tested, except methotrexate. Tumours were considered sensitive when the drug concentration required to inhibit colony formation by 50%, was less than 1/10 of the peak plasma concentration in patients. All H & N tumour lines were resistant to cisplatin, doxorubicin, hydroxyurea, mafosfamide (an in vitro active analogue of cyclophosphamide) and methotrexate. Bleomycin was active in 1/6 and 5-fluorouracil in 6/6 of the H & N tumour lines tested. In 32 cases the in vitro data of the H & N tumour lines and a chemosensitive rat rhabdomyosarcoma were compared directly with in vivo results obtained in nude mice. The clonogenic assay correctly predicted sensitivity in 4/6 (66.7%) and resistance in 21/26 (80.8%) of the cases. A lack of correlation was noted for methotrexate, 5-fluorouracil and cyclophosphamide. In vitro culture of human H & N xenografts may provide a means for a rapid and large scale screening to identify new drugs active against H & N malignancies. In addition the clonogenic assay may help to select drugs for subsequent testing in the nude mouse xenograft model. The lack of correlation for some drugs in the present study indicates that there are some limitations in the use of xenograft tumour material for in vitro testing of new drugs.
D000818:Animals; D002945:Cisplatin / Q000627:therapeutic use; D003520:Cyclophosphamide / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000627:therapeutic use; D004351:Drug Resistance; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D006258:Head and Neck Neoplasms / Q000188:drug therapy*; D006801:Humans; D006918:Hydroxyurea / Q000627:therapeutic use; D066298:In Vitro Techniques; D008727:Methotrexate / Q000627:therapeutic use; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D051381:Rats; D014410:Tumor Stem Cell Assay
D004317:Doxorubicin; D003520:Cyclophosphamide; D002945:Cisplatin; D005472:Fluorouracil; D006918:Hydroxyurea; D008727:Methotrexate