title: Docetaxel, carboplatin and concomitant radiotherapy for unresectable squamous cell carcinoma of the head and neck: pharmacokinetic and clinical data of a phase I-II study.
abstract: Concomitant chemoradiotherapy is the most effective treatment of unresectable head and neck cancer. Docetaxel and carboplatin are two active drugs that potentiate radiotherapy. Thirty patients (median age = 56 years; median Eastern Cooperative Oncology Group performance status = 1) received radiotherapy (70 Gy, 2 Gy/d, 5 d/wk) concurrent with carboplatin AUC 0.3 to 0.5 on day 1-5, weeks 1, 3, 5, 7, and docetaxel 15 to 25 mg/m2 on day 4 of weeks 2, 4, and 6. Site of unresectable squamous cell carcinoma was as follows: oropharynx, 41%; hypopharynx, 27%; oral cavity, 16%; and larynx, 16%. Stage was III in 13% and IV in 87%. In 11 patients, pharmacokinetic parameters were evaluated. Acute G4 toxicity was as follows: neutropenia, 20%; mucositis, 33%. We had the following acute G3 toxicities: mucositis, 40%; neutropenia, 37%; dermatitis, 23%; and anemia, 13%. The maximum tolerated dosage was area under the curve 0.5 for carboplatin and 20 mg/m2 for docetaxel. Median radiotherapy dose was 69 Gy, and 175 out of 210 courses (83%) were administered. At the end of the treatment, we had 20 complete responses (CR) (67%), 9 partial responses (30%), and 1 no change (3%). After radial neck dissection, 2 patients achieved a CR (overall CR = 73%). After a median follow-up of 2.5 years, we had a 3-year local progression-free survival of 85%, failure-free survival of 69%, and overall survival of 60%. A significant increase of Cmax of carboplatin concentration was noted at the beginning of weeks 3, 5, and 7. Total plasma platinum raises during each course of 5 days of carboplatin without reaching a steady state. Carboplatin, docetaxel, and concomitant conventional radiotherapy is a feasible and effective treatment of unresectable head and neck cancer. The concurrent administration of two drugs does not alter pharmacokinetic drug behavior compared with single-agent data.
authors.affiliation: Department of Medical Oncology, San Giovanni Antica Sede Hospital, Torino, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Airoldi
authors.forename: Luigi
authors.initials: L
authors.lastname: Cattel
authors.forename: Giorgio
authors.initials: G
authors.lastname: Cortesina
authors.forename: Carlo
authors.initials: C
authors.lastname: Giordano
authors.forename: Fulvia
authors.initials: F
authors.lastname: Pedani
authors.forename: Valeria
authors.initials: V
authors.lastname: Recalenda
authors.forename: Marco
authors.initials: M
authors.lastname: Danova
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Gabriele
authors.forename: Valeria
authors.initials: V
authors.lastname: Tagini
authors.forename: Camillo
authors.initials: C
authors.lastname: Porta
authors.forename: Cesare
authors.initials: C
authors.lastname: Bumma
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D019540:Area Under Curve; D016190:Carboplatin / Q000008:administration & dosage / Q000493:pharmacokinetics; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000378:metabolism / Q000532:radiotherapy; D003131:Combined Modality Therapy; D000077143:Docetaxel; D005260:Female; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000532:radiotherapy; D006801:Humans; D008297:Male; D008875:Middle Aged; D011879:Radiotherapy Dosage; D011880:Radiotherapy Planning, Computer-Assisted; D016019:Survival Analysis; D043823:Taxoids / Q000008:administration & dosage / Q000493:pharmacokinetics; D016896:Treatment Outcome
chemical_list: D043823:Taxoids; D000077143:Docetaxel; D016190:Carboplatin