title: Neoadjuvant chemotherapy followed by concurrent chemo-radiation therapy in locally advanced nasopharyngeal carcinoma.
abstract: OBJECTIVE
  To evaluate the efficacy and outcomes of neoadjuvant cisplatinum and epirubicin chemotherapy followed by concurrent cisplatinum chemotherapy with radiotherapy in patients with locally advanced nasopharyngeal carcinoma.
  
  
  METHODS
  One hundred ten patients (80 male, 30 female) with locally advanced nasopharyngeal carcinoma, staged according to the 1997 International Union Against Cancer/American Joint Committee on Cancer classification system as IIB (n = 9), III (n = 20), IVA (n = 32), and IVB (n = 49), World Health Organization types II (n = 25) and III (n = 85), were included in this protocol between January 1998 and July 2000 at King Faisal Specialist Hospital and Research Centre. Patients underwent two cycles of induction chemotherapy with cisplatinum 100 mg/m(2) and epirubicin 70 mg/m(2) on Days 1 and 21, followed by a radical course of radiotherapy (6,600 cGy in 6.5 weeks, 200 cGy/fraction) starting on Day 42, with three cycles of concurrent cisplatinum 25 mg/m(2) for 4 days on Days 42, 63, and 84.
  
  
  RESULTS
  Of 110 patients included in this study, intracranial extension was present in 32 (29%), and nodal stage was N3 in 49 (45%). Complete remission and partial remission were achieved in 87 patients (79%) and 23 patients (21%), respectively. At a median follow-up for surviving patients of 37 months (22-55 months), 49 of 110 patients (44%) had failed treatment: 12 with local, 9 with regional nodes, 4 locoregional, 5 locoregional plus distant areas, and 19 with distant metastases. At the time of writing, 34 patients had died; all deaths were related to the patients' cancer except for 1 patient with treatment-related toxicity. Three-year actuarial overall survival, relapse-free survival, locoregional control, and distant metastasis-free survival rates were 89%, 78%, 88%, and 89% for patients with stage IIB; 71%, 70%, 89%, and 74% for stage III; 68%, 49%, 61%, and 77% for stage IVA; and 70%, 45%, 60%, and 69% for stage IVB, respectively. One patient received only one induction cycle; all others received two cycles; however, 9 of them required 20% reduction in the second cycle dose. Ninety patients (82%) completed two or more concurrent cycles of cisplatinum. Rates of Grade 3 and 4 reactions after induction chemotherapy were as follows: anemia 1% and 0%, leukopenia 8% and 4%, nausea 27% and 0%, vomiting 25% and 0%, and infection 4% and 4%, respectively. Acute Grade 3 and 4 reactions were also observed during chemoradiotherapy: anemia 1% and 0%, leukopenia 31% and 4%, nausea 35% and 0%, vomiting 26% and 2%, infection in 4% and 2%, mucositis in 49% and 0%, and skin reaction in 39% and 0%, respectively.
  
  
  CONCLUSIONS
  Neoadjuvant chemotherapy followed by concurrent chemoradiotherapy is a safe and effective method of treatment for locally advanced nasopharyngeal carcinoma. Further investigations in prospective studies are required to evaluate this regimen.
authors.affiliation: Division of Radiation Oncology, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.
authors.forename: Abdullah
authors.initials: A
authors.lastname: Al-Amro
authors.forename: Nasser
authors.initials: N
authors.lastname: Al-Rajhi
authors.forename: Yasser
authors.initials: Y
authors.lastname: Khafaga
authors.forename: Mohammad
authors.initials: M
authors.lastname: Memon
authors.forename: Adnan
authors.initials: A
authors.lastname: Al-Hebshi
authors.forename: Ashraf
authors.initials: A
authors.lastname: El-Enbabi
authors.forename: Gamal
authors.initials: G
authors.lastname: El-Husseiny
authors.forename: Amer
authors.initials: A
authors.lastname: Radawi
authors.forename: Abdulaziz
authors.initials: A
authors.lastname: Belal
authors.forename: Ayman
authors.initials: A
authors.lastname: Allam
authors.forename: Medhat
authors.initials: M
authors.lastname: El-Sebaie
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D002945:Cisplatin / Q000008:administration & dosage; D015251:Epirubicin / Q000008:administration & dosage; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009303:Nasopharyngeal Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D009367:Neoplasm Staging; D012074:Remission Induction; D017211:Treatment Failure
chemical_list: D015251:Epirubicin; D002945:Cisplatin