title: Evaluation of optimal drug concentration in histoculture drug response assay in association with clinical efficacy for head and neck cancer.
abstract: Induction chemotherapy or concomitant chemoradiotherapy has been used increasingly to improve survival, organ preservation and function in patients with head and neck cancer (HNC). However, this regimen encounters significant side effects with potential adverse reactions causing many disadvantages for patients. Therefore, reliable chemosensitivity assays are needed to accurately predict the response to chemotherapy and guide the selection and treatment of patients with HNC. The main purpose of this study was to examine the optimal drug concentrations for evaluating in vitro chemosensitivity using the histoculture drug response assay (HDRA). The tested tumor specimens included 7 from oral cavities (14.3%), 12 from oropharynx (24.5%), 10 hypopharynx (20.4%), 3 larynx (6.1%), 5 sinonasal (10.2%), 2 salivary glands (4.1%), and 10 from metastatic lymph nodes (20.4%), respectively. Histopathologic types of all 49 specimens were squamous cell carcinoma. We investigated the optimal drug concentrations in HDRA searching at doses of 4-100 microg/ml for cisplatin and 60-1500 microg/ml for 5-FU. We considered the concentration of 20 microg/ml to be appropriate for evaluating cisplatin sensitivity in HNC among the tested dosages. As for cisplatin sensitivity in vitro, the 50% cut-off inhibition index (I.I.) was found to have a significant association with the clinical response to chemotherapy, with an accurate prediction rate of 77.8%. The HDRA shows a predictive value for chemosensitivity in HNC patients using the optimal drug concentration cut-off with this site specificity.
authors.affiliation: Department of Head and Neck Surgery, Aichi Cancer Center, 1-1 Kanokoden Chikusaku, Nagoya 464-8681, Japan. hasegawa@aichi-cc.jp
authors.forename: Yasuhisa
authors.initials: Y
authors.lastname: Hasegawa
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Goto
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Hanai
authors.forename: Kei
authors.initials: K
authors.lastname: Ijichi
authors.forename: Makoto
authors.initials: M
authors.lastname: Adachi
authors.forename: Akihiro
authors.initials: A
authors.lastname: Terada
authors.forename: Ikuo
authors.initials: I
authors.lastname: Hyodo
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Ogawa
authors.forename: Tomoko
authors.initials: T
authors.lastname: Furukawa
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000494:pharmacology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D002945:Cisplatin / Q000008:administration & dosage / Q000494:pharmacology; D003131:Combined Modality Therapy; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor / Q000379:methods*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000494:pharmacology; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D012189:Retrospective Studies; D016896:Treatment Outcome; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D002945:Cisplatin; D005472:Fluorouracil