title: Dose-finding study of docetaxel added to ifosfamide and cisplatin followed by concomitant capecitabine and radiotherapy in the treatment of locally advanced squamous cell carcinoma of the head and neck.
abstract: BACKGROUND
  Docetaxel (DOC) is a promising new drug in the management of squamous cell carcinoma of the head and neck. The aim of this phase I study was to determine the toxicity and maximum tolerated dose (MTD) as well as to obtain preliminary data on the activity of DOC combined with fixed doses of ifosfamide (IFO) and cisplatin (CDDP), followed by concomitant capecitabine (C) and radiation therapy in the organ-sparing treatment of patients with locally advanced, inoperable squamous cell carcinoma of the head and neck (A-SCCHN).
  
  
  METHODS
  Chemotherapy and radiotherapy-naive patients with A-SCCHN were treated in cohorts of three with escalating doses of DOC administered on day 1. The doses of DOC ranged from 40 mg/m2 up to the dose-limiting toxicity (DTL). Fixed doses of IFO (1200 mg/m2) with mesna and CDDP (20 mg/m2) were administered on days 1 to 4, every 4 weeks. Patients who had achieved a response received definitive radiation therapy (6000 cGy) concomitantly with C (1000 mg/m2/day).
  
  
  RESULTS
  Twenty-four patients were entered into the study. The MTD of DOC was 70 mg/m2. A total of 99 courses of chemotherapy were given. Grade 3 and 4 hematological toxicities were observed in twelve and nine patients, respectively, while grade 3 gastrointestinal toxicity occurred in four patients. Concomitant C and radiation therapy demonstrated a tolerable toxicity profile. An overall response rate of 83.3% (95% CI: 65.6% to 95.2%) was obtained, with a median time to progression and overall survival of 15.6 and 22.3 months, respectively.
  
  
  CONCLUSIONS
  Out-patient administration of DOC, IFO and CDDP for A-SCCHN was safe and did not affect the ability to administer chemoradiotherapy on schedule. Myelosuppression was the DLT.
authors.affiliation: ALS-1 Ospedale Civile di Avezzano, Divisione di Oncologia, Monterotondo, Roma, Italy. frecchia1946@libero.it
authors.forename: Francesco
authors.initials: F
authors.lastname: Recchia
authors.forename: Gaetano
authors.initials: G
authors.lastname: Saggio
authors.forename: Alisia
authors.initials: A
authors.lastname: Cesta
authors.forename: Giovanna
authors.initials: G
authors.lastname: Amiconi
authors.forename: Anna
authors.initials: A
authors.lastname: di Blasio
authors.forename: Giampiero
authors.initials: G
authors.lastname: Candeloro
authors.forename: Maurizio
authors.initials: M
authors.lastname: Valeriani
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Tombolini
authors.forename: Silvio
authors.initials: S
authors.lastname: Rea
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use*; D000069287:Capecitabine; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy / Q000009:adverse effects; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000077143:Docetaxel; D004305:Dose-Response Relationship, Drug; D005240:Feasibility Studies; D005260:Female; D005472:Fluorouracil / Q000031:analogs & derivatives; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011878:Radiotherapy / Q000009:adverse effects; D015996:Survival Rate; D043823:Taxoids / Q000008:administration & dosage
chemical_list: D043823:Taxoids; D003841:Deoxycytidine; D000077143:Docetaxel; D000069287:Capecitabine; D002945:Cisplatin; D005472:Fluorouracil; D007069:Ifosfamide