title: Phase I study of concomitant chemoradiotherapy with irinotecan, 5-FU, and hydroxyurea for patients with advanced and/or recurrent head and neck cancer.
abstract: OBJECTIVE
  We sought to investigate CPT-11 as a promising agent to our established regimen of 5-fluorouracil (5-FU), hydroxyurea, and hyperfractionated radiation therapy. A phase I study was conducted to determine the maximum tolerated dose and dose-limiting toxicities of this regimen.
  
  
  METHODS
  Eligible patients included patients with poor prognosis advanced head and neck cancer who required radiation therapy. All patients were treated on a 14-day cycle. Each patient received 5-FU (600 mg/m(2)/d), hydroxyurea (500 mg orally every 12 hours), radiation therapy twice daily (150 cGy each fraction), and CPT-11 at a starting dose of 5 mg/m(2)/d for 5 consecutive days followed by a 9-day break. CPT-11 was escalated in five mg/m(2)/d increments. Dose-limiting toxicity was defined as grade 4 hematologic toxicity, persistent grade 4 dermatitis and mucositis, grade 4 diarrhea despite maximal pharmacologic intervention, and inability to receive full-dose chemotherapy with the next cycle of treatment. Fourteen patients were treated at maximum tolerated dose to verify the recommended phase II dose.
  
  
  RESULTS
  Between August 1998 and August 2001, 31 patients with advanced and/or recurrent head and neck cancer were enrolled. Cohorts of nine, four, three, and 14 patients were treated at 5-, 10-, 15-, and 10-mg/m(2)/d dose levels of CPT-11. The 5- and 10-mg/m(2)/d dose levels were well tolerated All three patients treated at 15 mg/m(2)/d experienced neutropenic dose-limiting toxicity during cycles 1-2.
  
  
  CONCLUSIONS
  The maximum tolerated dose and recommended phase II dose of CPT-11 with hyperfractionated radiation therapy is 10 mg/m(2)/d.
authors.affiliation: Departments of Radiation and Cellular Oncology, University of Chicago, 5758 S. Maryland Avenue, Chicago, IL 60637-1470, USA.
authors.forename: Joseph K
authors.initials: JK
authors.lastname: Salama
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Haraf
authors.forename: Kerstin
authors.initials: K
authors.lastname: Stenson
authors.forename: Michael T
authors.initials: MT
authors.lastname: Milano
authors.forename: Mary Ellyn
authors.initials: ME
authors.lastname: Witt
authors.forename: Everett E
authors.initials: EE
authors.lastname: Vokes
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D003131:Combined Modality Therapy; D019583:Dose Fractionation, Radiation; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D006801:Humans; D006918:Hydroxyurea / Q000008:administration & dosage; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000532:radiotherapy; D009367:Neoplasm Staging; D020266:Radiotherapy, Conformal
chemical_list: D000077146:Irinotecan; D005472:Fluorouracil; D006918:Hydroxyurea; D002166:Camptothecin