title: Phase III randomized trial of induction chemotherapy in patients with N2 or N3 locally advanced head and neck cancer.
abstract: OBJECTIVE
  Induction chemotherapy (IC) before radiotherapy lowers distant failure (DF) rates in locally advanced squamous cell carcinoma of the head and neck (SCCHN). The goal of this phase III trial was to determine whether IC before chemoradiotherapy (CRT) further improves survival compared with CRT alone in patients with N2 or N3 disease.
  
  
  METHODS
  Treatment-naive patients with nonmetastatic N2 or N3 SCCHN were randomly assigned to CRT alone (CRT arm; docetaxel, fluorouracil, and hydroxyurea plus radiotherapy 0.15 Gy twice per day every other week) versus two 21-day cycles of IC (docetaxel 75 mg/m(2) on day 1, cisplatin 75 mg/m(2) on day 1, and fluorouracil 750 mg/m(2) on days 1 to 5) followed by the same CRT regimen (IC + CRT arm). The primary end point was overall survival (OS). Secondary end points included DF-free survival, failure pattern, and recurrence-free survival (RFS).
  
  
  RESULTS
  A total of 285 patients were randomly assigned. The most common grade 3 to 4 toxicities during IC were febrile neutropenia (11%) and mucositis (9%); during CRT (both arms combined), they were mucositis (49%), dermatitis (21%), and leukopenia (18%). Serious adverse events were more common in the IC arm (47% v 28%; P = .002). With a minimum follow-up of 30 months, there were no statistically significant differences in OS (hazard ratio, 0.91; 95% CI, 0.59 to 1.41), RFS, or DF-free survival.
  
  
  CONCLUSIONS
  IC did not translate into improved OS compared with CRT alone. However, the study was underpowered because it did not meet the planned accrual target, and OS was higher than predicted in both arms. IC cannot be recommended routinely in patients with N2 or N3 locally advanced SCCHN.
authors: Ezra E.W. Cohen, Theodore G. Karrison, Masha Kocherginsky, Jeffrey Mueller, Robyn Egan, Tanguy Y. Seiwert, Victoria M. Villaflor, Daniel J. Haraf, and Everett E. Vokes, University of Chicago, Chicago; Bruce E. Brockstein, North Shore University Health System, Evanston; Mark B. Agulnik and Bharat B. Mittal, Northwestern University, Chicago, IL; Chao H. Huang, University of Kansas and Veterans Affairs Medical Center, Kansas City, KS; Furhan Yunus and Sandeep Samant, University of Tennessee, Memphis, TN; Luis E. Raez, University of Miami, Miami, FL; Ranee Mehra, Fox Chase Cancer Center, Philadelphia, PA; Priya Kumar and Frank Ondrey, University of Minnesota, Minneapolis, MN; and Patrice Marchand and Bettina Braegas, Nuvisan Oncology, Le Kremlin-Bicêtre, France. ecohen@ucsd.edu.
authors: Ezra E W
authors: EE
authors: Cohen
authors: Ezra E.W. Cohen, Theodore G. Karrison, Masha Kocherginsky, Jeffrey Mueller, Robyn Egan, Tanguy Y. Seiwert, Victoria M. Villaflor, Daniel J. Haraf, and Everett E. Vokes, University of Chicago, Chicago; Bruce E. Brockstein, North Shore University Health System, Evanston; Mark B. Agulnik and Bharat B. Mittal, Northwestern University, Chicago, IL; Chao H. Huang, University of Kansas and Veterans Affairs Medical Center, Kansas City, KS; Furhan Yunus and Sandeep Samant, University of Tennessee, Memphis, TN; Luis E. Raez, University of Miami, Miami, FL; Ranee Mehra, Fox Chase Cancer Center, Philadelphia, PA; Priya Kumar and Frank Ondrey, University of Minnesota, Minneapolis, MN; and Patrice Marchand and Bettina Braegas, Nuvisan Oncology, Le Kremlin-Bicêtre, France.
authors: Theodore G
authors: TG
authors: Karrison
authors: Ezra E.W. Cohen, Theodore G. Karrison, Masha Kocherginsky, Jeffrey Mueller, Robyn Egan, Tanguy Y. Seiwert, Victoria M. Villaflor, Daniel J. Haraf, and Everett E. Vokes, University of Chicago, Chicago; Bruce E. Brockstein, North Shore University Health System, Evanston; Mark B. Agulnik and Bharat B. Mittal, Northwestern University, Chicago, IL; Chao H. Huang, University of Kansas and Veterans Affairs Medical Center, Kansas City, KS; Furhan Yunus and Sandeep Samant, University of Tennessee, Memphis, TN; Luis E. Raez, University of Miami, Miami, FL; Ranee Mehra, Fox Chase Cancer Center, Philadelphia, PA; Priya Kumar and Frank Ondrey, University of Minnesota, Minneapolis, MN; and Patrice Marchand and Bettina Braegas, Nuvisan Oncology, Le Kremlin-Bicêtre, France.
authors: Masha
authors: M
authors: Kocherginsky
authors: Ezra E.W. Cohen, Theodore G. Karrison, Masha Kocherginsky, Jeffrey Mueller, Robyn Egan, Tanguy Y. Seiwert, Victoria M. Villaflor, Daniel J. Haraf, and Everett E. Vokes, University of Chicago, Chicago; Bruce E. Brockstein, North Shore University Health System, Evanston; Mark B. Agulnik and Bharat B. Mittal, Northwestern University, Chicago, IL; Chao H. Huang, University of Kansas and Veterans Affairs Medical Center, Kansas City, KS; Furhan Yunus and Sandeep Samant, University of Tennessee, Memphis, TN; Luis E. Raez, University of Miami, Miami, FL; Ranee Mehra, Fox Chase Cancer Center, Philadelphia, PA; Priya Kumar and Frank Ondrey, University of Minnesota, Minneapolis, MN; and Patrice Marchand and Bettina Braegas, Nuvisan Oncology, Le Kremlin-Bicêtre, France.
authors: Jeffrey
authors: J
authors: Mueller
authors: Ezra E.W. Cohen, Theodore G. Karrison, Masha Kocherginsky, Jeffrey Mueller, Robyn Egan, Tanguy Y. Seiwert, Victoria M. Villaflor, Daniel J. Haraf, and Everett E. Vokes, University of Chicago, Chicago; Bruce E. Brockstein, North Shore University Health System, Evanston; Mark B. Agulnik and Bharat B. Mittal, Northwestern University, Chicago, IL; Chao H. Huang, University of Kansas and Veterans Affairs Medical Center, Kansas City, KS; Furhan Yunus and Sandeep Samant, University of Tennessee, Memphis, TN; Luis E. Raez, University of Miami, Miami, FL; Ranee Mehra, Fox Chase Cancer Center, Philadelphia, PA; Priya Kumar and Frank Ondrey, University of Minnesota, Minneapolis, MN; and Patrice Marchand and Bettina Braegas, Nuvisan Oncology, Le Kremlin-Bicêtre, France.
authors: Robyn
authors: R
authors: Egan
authors: Ezra E.W. Cohen, Theodore G. Karrison, Masha Kocherginsky, Jeffrey Mueller, Robyn Egan, Tanguy Y. Seiwert, Victoria M. Villaflor, Daniel J. Haraf, and Everett E. Vokes, University of Chicago, Chicago; Bruce E. Brockstein, North Shore University Health System, Evanston; Mark B. Agulnik and Bharat B. Mittal, Northwestern University, Chicago, IL; Chao H. Huang, University of Kansas and Veterans Affairs Medical Center, Kansas City, KS; Furhan Yunus and Sandeep Samant, University of Tennessee, Memphis, TN; Luis E. Raez, University of Miami, Miami, FL; Ranee Mehra, Fox Chase Cancer Center, Philadelphia, PA; Priya Kumar and Frank Ondrey, University of Minnesota, Minneapolis, MN; and Patrice Marchand and Bettina Braegas, Nuvisan Oncology, Le Kremlin-Bicêtre, France.
authors: Chao H
authors: CH
authors: Huang
authors: Ezra E.W. Cohen, Theodore G. Karrison, Masha Kocherginsky, Jeffrey Mueller, Robyn Egan, Tanguy Y. Seiwert, Victoria M. Villaflor, Daniel J. Haraf, and Everett E. Vokes, University of Chicago, Chicago; Bruce E. Brockstein, North Shore University Health System, Evanston; Mark B. Agulnik and Bharat B. Mittal, Northwestern University, Chicago, IL; Chao H. Huang, University of Kansas and Veterans Affairs Medical Center, Kansas City, KS; Furhan Yunus and Sandeep Samant, University of Tennessee, Memphis, TN; Luis E. Raez, University of Miami, Miami, FL; Ranee Mehra, Fox Chase Cancer Center, Philadelphia, PA; Priya Kumar and Frank Ondrey, University of Minnesota, Minneapolis, MN; and Patrice Marchand and Bettina Braegas, Nuvisan Oncology, Le Kremlin-Bicêtre, France.
authors: Bruce E
authors: BE
authors: Brockstein
authors: Ezra E.W. Cohen, Theodore G. Karrison, Masha Kocherginsky, Jeffrey Mueller, Robyn Egan, Tanguy Y. Seiwert, Victoria M. Villaflor, Daniel J. Haraf, and Everett E. Vokes, University of Chicago, Chicago; Bruce E. Brockstein, North Shore University Health System, Evanston; Mark B. Agulnik and Bharat B. Mittal, Northwestern University, Chicago, IL; Chao H. Huang, University of Kansas and Veterans Affairs Medical Center, Kansas City, KS; Furhan Yunus and Sandeep Samant, University of Tennessee, Memphis, TN; Luis E. Raez, University of Miami, Miami, FL; Ranee Mehra, Fox Chase Cancer Center, Philadelphia, PA; Priya Kumar and Frank Ondrey, University of Minnesota, Minneapolis, MN; and Patrice Marchand and Bettina Braegas, Nuvisan Oncology, Le Kremlin-Bicêtre, France.
authors: Mark B
authors: MB
authors: Agulnik
authors: Ezra E.W. Cohen, Theodore G. Karrison, Masha Kocherginsky, Jeffrey Mueller, Robyn Egan, Tanguy Y. Seiwert, Victoria M. Villaflor, Daniel J. Haraf, and Everett E. Vokes, University of Chicago, Chicago; Bruce E. Brockstein, North Shore University Health System, Evanston; Mark B. Agulnik and Bharat B. Mittal, Northwestern University, Chicago, IL; Chao H. Huang, University of Kansas and Veterans Affairs Medical Center, Kansas City, KS; Furhan Yunus and Sandeep Samant, University of Tennessee, Memphis, TN; Luis E. Raez, University of Miami, Miami, FL; Ranee Mehra, Fox Chase Cancer Center, Philadelphia, PA; Priya Kumar and Frank Ondrey, University of Minnesota, Minneapolis, MN; and Patrice Marchand and Bettina Braegas, Nuvisan Oncology, Le Kremlin-Bicêtre, France.
authors: Bharat B
authors: BB
authors: Mittal
authors: Ezra E.W. Cohen, Theodore G. Karrison, Masha Kocherginsky, Jeffrey Mueller, Robyn Egan, Tanguy Y. Seiwert, Victoria M. Villaflor, Daniel J. Haraf, and Everett E. Vokes, University of Chicago, Chicago; Bruce E. Brockstein, North Shore University Health System, Evanston; Mark B. Agulnik and Bharat B. Mittal, Northwestern University, Chicago, IL; Chao H. Huang, University of Kansas and Veterans Affairs Medical Center, Kansas City, KS; Furhan Yunus and Sandeep Samant, University of Tennessee, Memphis, TN; Luis E. Raez, University of Miami, Miami, FL; Ranee Mehra, Fox Chase Cancer Center, Philadelphia, PA; Priya Kumar and Frank Ondrey, University of Minnesota, Minneapolis, MN; and Patrice Marchand and Bettina Braegas, Nuvisan Oncology, Le Kremlin-Bicêtre, France.
authors: Furhan
authors: F
authors: Yunus
authors: Ezra E.W. Cohen, Theodore G. Karrison, Masha Kocherginsky, Jeffrey Mueller, Robyn Egan, Tanguy Y. Seiwert, Victoria M. Villaflor, Daniel J. Haraf, and Everett E. Vokes, University of Chicago, Chicago; Bruce E. Brockstein, North Shore University Health System, Evanston; Mark B. Agulnik and Bharat B. Mittal, Northwestern University, Chicago, IL; Chao H. Huang, University of Kansas and Veterans Affairs Medical Center, Kansas City, KS; Furhan Yunus and Sandeep Samant, University of Tennessee, Memphis, TN; Luis E. Raez, University of Miami, Miami, FL; Ranee Mehra, Fox Chase Cancer Center, Philadelphia, PA; Priya Kumar and Frank Ondrey, University of Minnesota, Minneapolis, MN; and Patrice Marchand and Bettina Braegas, Nuvisan Oncology, Le Kremlin-Bicêtre, France.
authors: Sandeep
authors: S
authors: Samant
authors: Ezra E.W. Cohen, Theodore G. Karrison, Masha Kocherginsky, Jeffrey Mueller, Robyn Egan, Tanguy Y. Seiwert, Victoria M. Villaflor, Daniel J. Haraf, and Everett E. Vokes, University of Chicago, Chicago; Bruce E. Brockstein, North Shore University Health System, Evanston; Mark B. Agulnik and Bharat B. Mittal, Northwestern University, Chicago, IL; Chao H. Huang, University of Kansas and Veterans Affairs Medical Center, Kansas City, KS; Furhan Yunus and Sandeep Samant, University of Tennessee, Memphis, TN; Luis E. Raez, University of Miami, Miami, FL; Ranee Mehra, Fox Chase Cancer Center, Philadelphia, PA; Priya Kumar and Frank Ondrey, University of Minnesota, Minneapolis, MN; and Patrice Marchand and Bettina Braegas, Nuvisan Oncology, Le Kremlin-Bicêtre, France.
authors: Luis E
authors: LE
authors: Raez
authors: Ezra E.W. Cohen, Theodore G. Karrison, Masha Kocherginsky, Jeffrey Mueller, Robyn Egan, Tanguy Y. Seiwert, Victoria M. Villaflor, Daniel J. Haraf, and Everett E. Vokes, University of Chicago, Chicago; Bruce E. Brockstein, North Shore University Health System, Evanston; Mark B. Agulnik and Bharat B. Mittal, Northwestern University, Chicago, IL; Chao H. Huang, University of Kansas and Veterans Affairs Medical Center, Kansas City, KS; Furhan Yunus and Sandeep Samant, University of Tennessee, Memphis, TN; Luis E. Raez, University of Miami, Miami, FL; Ranee Mehra, Fox Chase Cancer Center, Philadelphia, PA; Priya Kumar and Frank Ondrey, University of Minnesota, Minneapolis, MN; and Patrice Marchand and Bettina Braegas, Nuvisan Oncology, Le Kremlin-Bicêtre, France.
authors: Ranee
authors: R
authors: Mehra
authors: Ezra E.W. Cohen, Theodore G. Karrison, Masha Kocherginsky, Jeffrey Mueller, Robyn Egan, Tanguy Y. Seiwert, Victoria M. Villaflor, Daniel J. Haraf, and Everett E. Vokes, University of Chicago, Chicago; Bruce E. Brockstein, North Shore University Health System, Evanston; Mark B. Agulnik and Bharat B. Mittal, Northwestern University, Chicago, IL; Chao H. Huang, University of Kansas and Veterans Affairs Medical Center, Kansas City, KS; Furhan Yunus and Sandeep Samant, University of Tennessee, Memphis, TN; Luis E. Raez, University of Miami, Miami, FL; Ranee Mehra, Fox Chase Cancer Center, Philadelphia, PA; Priya Kumar and Frank Ondrey, University of Minnesota, Minneapolis, MN; and Patrice Marchand and Bettina Braegas, Nuvisan Oncology, Le Kremlin-Bicêtre, France.
authors: Priya
authors: P
authors: Kumar
authors: Ezra E.W. Cohen, Theodore G. Karrison, Masha Kocherginsky, Jeffrey Mueller, Robyn Egan, Tanguy Y. Seiwert, Victoria M. Villaflor, Daniel J. Haraf, and Everett E. Vokes, University of Chicago, Chicago; Bruce E. Brockstein, North Shore University Health System, Evanston; Mark B. Agulnik and Bharat B. Mittal, Northwestern University, Chicago, IL; Chao H. Huang, University of Kansas and Veterans Affairs Medical Center, Kansas City, KS; Furhan Yunus and Sandeep Samant, University of Tennessee, Memphis, TN; Luis E. Raez, University of Miami, Miami, FL; Ranee Mehra, Fox Chase Cancer Center, Philadelphia, PA; Priya Kumar and Frank Ondrey, University of Minnesota, Minneapolis, MN; and Patrice Marchand and Bettina Braegas, Nuvisan Oncology, Le Kremlin-Bicêtre, France.
authors: Frank
authors: F
authors: Ondrey
authors: Ezra E.W. Cohen, Theodore G. Karrison, Masha Kocherginsky, Jeffrey Mueller, Robyn Egan, Tanguy Y. Seiwert, Victoria M. Villaflor, Daniel J. Haraf, and Everett E. Vokes, University of Chicago, Chicago; Bruce E. Brockstein, North Shore University Health System, Evanston; Mark B. Agulnik and Bharat B. Mittal, Northwestern University, Chicago, IL; Chao H. Huang, University of Kansas and Veterans Affairs Medical Center, Kansas City, KS; Furhan Yunus and Sandeep Samant, University of Tennessee, Memphis, TN; Luis E. Raez, University of Miami, Miami, FL; Ranee Mehra, Fox Chase Cancer Center, Philadelphia, PA; Priya Kumar and Frank Ondrey, University of Minnesota, Minneapolis, MN; and Patrice Marchand and Bettina Braegas, Nuvisan Oncology, Le Kremlin-Bicêtre, France.
authors: Patrice
authors: P
authors: Marchand
authors: Ezra E.W. Cohen, Theodore G. Karrison, Masha Kocherginsky, Jeffrey Mueller, Robyn Egan, Tanguy Y. Seiwert, Victoria M. Villaflor, Daniel J. Haraf, and Everett E. Vokes, University of Chicago, Chicago; Bruce E. Brockstein, North Shore University Health System, Evanston; Mark B. Agulnik and Bharat B. Mittal, Northwestern University, Chicago, IL; Chao H. Huang, University of Kansas and Veterans Affairs Medical Center, Kansas City, KS; Furhan Yunus and Sandeep Samant, University of Tennessee, Memphis, TN; Luis E. Raez, University of Miami, Miami, FL; Ranee Mehra, Fox Chase Cancer Center, Philadelphia, PA; Priya Kumar and Frank Ondrey, University of Minnesota, Minneapolis, MN; and Patrice Marchand and Bettina Braegas, Nuvisan Oncology, Le Kremlin-Bicêtre, France.
authors: Bettina
authors: B
authors: Braegas
authors: Ezra E.W. Cohen, Theodore G. Karrison, Masha Kocherginsky, Jeffrey Mueller, Robyn Egan, Tanguy Y. Seiwert, Victoria M. Villaflor, Daniel J. Haraf, and Everett E. Vokes, University of Chicago, Chicago; Bruce E. Brockstein, North Shore University Health System, Evanston; Mark B. Agulnik and Bharat B. Mittal, Northwestern University, Chicago, IL; Chao H. Huang, University of Kansas and Veterans Affairs Medical Center, Kansas City, KS; Furhan Yunus and Sandeep Samant, University of Tennessee, Memphis, TN; Luis E. Raez, University of Miami, Miami, FL; Ranee Mehra, Fox Chase Cancer Center, Philadelphia, PA; Priya Kumar and Frank Ondrey, University of Minnesota, Minneapolis, MN; and Patrice Marchand and Bettina Braegas, Nuvisan Oncology, Le Kremlin-Bicêtre, France.
authors: Tanguy Y
authors: TY
authors: Seiwert
authors: Ezra E.W. Cohen, Theodore G. Karrison, Masha Kocherginsky, Jeffrey Mueller, Robyn Egan, Tanguy Y. Seiwert, Victoria M. Villaflor, Daniel J. Haraf, and Everett E. Vokes, University of Chicago, Chicago; Bruce E. Brockstein, North Shore University Health System, Evanston; Mark B. Agulnik and Bharat B. Mittal, Northwestern University, Chicago, IL; Chao H. Huang, University of Kansas and Veterans Affairs Medical Center, Kansas City, KS; Furhan Yunus and Sandeep Samant, University of Tennessee, Memphis, TN; Luis E. Raez, University of Miami, Miami, FL; Ranee Mehra, Fox Chase Cancer Center, Philadelphia, PA; Priya Kumar and Frank Ondrey, University of Minnesota, Minneapolis, MN; and Patrice Marchand and Bettina Braegas, Nuvisan Oncology, Le Kremlin-Bicêtre, France.
authors: Victoria M
authors: VM
authors: Villaflor
authors: Ezra E.W. Cohen, Theodore G. Karrison, Masha Kocherginsky, Jeffrey Mueller, Robyn Egan, Tanguy Y. Seiwert, Victoria M. Villaflor, Daniel J. Haraf, and Everett E. Vokes, University of Chicago, Chicago; Bruce E. Brockstein, North Shore University Health System, Evanston; Mark B. Agulnik and Bharat B. Mittal, Northwestern University, Chicago, IL; Chao H. Huang, University of Kansas and Veterans Affairs Medical Center, Kansas City, KS; Furhan Yunus and Sandeep Samant, University of Tennessee, Memphis, TN; Luis E. Raez, University of Miami, Miami, FL; Ranee Mehra, Fox Chase Cancer Center, Philadelphia, PA; Priya Kumar and Frank Ondrey, University of Minnesota, Minneapolis, MN; and Patrice Marchand and Bettina Braegas, Nuvisan Oncology, Le Kremlin-Bicêtre, France.
authors: Daniel J
authors: DJ
authors: Haraf
authors: Ezra E.W. Cohen, Theodore G. Karrison, Masha Kocherginsky, Jeffrey Mueller, Robyn Egan, Tanguy Y. Seiwert, Victoria M. Villaflor, Daniel J. Haraf, and Everett E. Vokes, University of Chicago, Chicago; Bruce E. Brockstein, North Shore University Health System, Evanston; Mark B. Agulnik and Bharat B. Mittal, Northwestern University, Chicago, IL; Chao H. Huang, University of Kansas and Veterans Affairs Medical Center, Kansas City, KS; Furhan Yunus and Sandeep Samant, University of Tennessee, Memphis, TN; Luis E. Raez, University of Miami, Miami, FL; Ranee Mehra, Fox Chase Cancer Center, Philadelphia, PA; Priya Kumar and Frank Ondrey, University of Minnesota, Minneapolis, MN; and Patrice Marchand and Bettina Braegas, Nuvisan Oncology, Le Kremlin-Bicêtre, France.
authors: Everett E
authors: EE
authors: Vokes
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000532:radiotherapy*; D059248:Chemoradiotherapy; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D000077143:Docetaxel; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*; D006801:Humans; D006918:Hydroxyurea / Q000008:administration & dosage / Q000009:adverse effects; D060828:Induction Chemotherapy; D008297:Male; D008875:Middle Aged; D000077195:Squamous Cell Carcinoma of Head and Neck; D015996:Survival Rate; D043823:Taxoids / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D043823:Taxoids; D000077143:Docetaxel; D002945:Cisplatin; D005472:Fluorouracil; D006918:Hydroxyurea