title: A preclinical model for experimental chemotherapy of human head and neck cancer.
abstract: We developed a mouse model in a representative human derived head and neck cancer cell line for preclinical studies to evaluate antitumor response, tumor-free survival and host toxicity of alkylating agents, antimetabolites, platinum analogs and taxanes alone or in combination. Ninety athymic NMRI mice were inoculated with human derived oral squamous cell carcinoma cells growing on the hind paw to an average volume of 180 +/- 80 mm3. Animals were stratified according to tumor volume into 10 groups (n=6-10) and treated with ifosfamide (65 mg/kg b.w.), docetaxel (24 mg/kg b.w.), cisplatin (2 mg/kg b.w.), carboplatin (6 or 10 mg/kg b.w.), methotrexate (1 mg/kg b.w.), and fluorouracil (15 mg/kg b.w.) intravenously in single agent or combination (ifosfamide plus docetaxel or ifosfamide plus carboplatin) treatment schedules or controls. Tumor volume was measured 3 times per week for 60 days. The average tumor volume, the overall survival time and the response rates (CR, PR) of the treated animals were compared with the data obtained from untreated controls and statistically evaluated. Untreated tumors showed rapid and exponential tumor growth. Single agent therapies with ifosfamide, cisplatinum, and docetaxel lead to significant tumor regression and improved overall survival. Low dose carboplatin monotherapy induced significant tumor growth delay, but not significant tumor regression. Most impressive tumor-free survival was achieved by combination treatment with ifosfamide and docetaxel. This preclinical study demonstrates an animal model capable of differentiating various chemotherapy regimens.
authors.affiliation: Department of Otorhinolaryngology, University Hospital Lubeck, D-23538 Lubeck, Germany. konrad.sommer@medinf.mu-luebeck.de
authors.forename: K
authors.initials: K
authors.lastname: Sommer
authors.forename: S O
authors.initials: SO
authors.lastname: Peters
authors.forename: I H
authors.initials: IH
authors.lastname: Robins
authors.forename: M
authors.initials: M
authors.lastname: Raap
authors.forename: G J
authors.initials: GJ
authors.lastname: Wiedemann
authors.forename: S
authors.initials: S
authors.lastname: Remmert
authors.forename: P
authors.initials: P
authors.lastname: Sieg
authors.forename: C
authors.initials: C
authors.lastname: Bittner
authors.forename: T
authors.initials: T
authors.lastname: Feyerabend
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001792:Blood Platelets / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D016190:Carboplatin / Q000008:administration & dosage; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000473:pathology; D002945:Cisplatin / Q000008:administration & dosage; D004195:Disease Models, Animal; D000077143:Docetaxel; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage; D008727:Methotrexate / Q000008:administration & dosage; D051379:Mice; D008819:Mice, Nude; D017239:Paclitaxel / Q000008:administration & dosage / Q000031:analogs & derivatives*; D015996:Survival Rate; D043823:Taxoids
chemical_list: D043823:Taxoids; D000077143:Docetaxel; D016190:Carboplatin; D017239:Paclitaxel; D002945:Cisplatin; D005472:Fluorouracil; D007069:Ifosfamide; D008727:Methotrexate