Phase III randomized trial of induction chemotherapy in patients with N2 or N3 locally advanced head and neck cancer

Ezra E.W. Cohen*, Theodore G. Karrison, Masha Kocherginsky, Jeffrey Mueller, Robyn Egan, Chao H. Huang, Bruce E. Brockstein, Mark B. Agulnik, Bharat B. Mittal, Furhan Yunus, Sandeep Samant, Luis E. Raez, Ranee Mehra, Priya Kumar, Frank Ondrey, Patrice Marchand, Bettina Braegas, Tanguy Y. Seiwert, Victoria M. Villaflor, Daniel J. Haraf & 1 others Everett E. Vokes

*Corresponding author for this work

Research output: Contribution to journalArticle

212 Citations (Scopus)

Abstract

Purpose: 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. Patients and 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/m2 on day 1, cisplatin 75 mg/m2 on day 1, and fluorouracil 750 mg/m2 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. Conclusion: 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.

Original languageEnglish (US)
Pages (from-to)2735-2743
Number of pages9
JournalJournal of Clinical Oncology
Volume32
Issue number25
DOIs
StatePublished - Sep 1 2014

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Induction Chemotherapy
Head and Neck Neoplasms
Chemoradiotherapy
Survival
docetaxel
Mucositis
Fluorouracil
Radiotherapy
Recurrence
Febrile Neutropenia
Hydroxyurea
Leukopenia
Dermatitis
Cisplatin

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Cohen, Ezra E.W. ; Karrison, Theodore G. ; Kocherginsky, Masha ; Mueller, Jeffrey ; Egan, Robyn ; Huang, Chao H. ; Brockstein, Bruce E. ; Agulnik, Mark B. ; Mittal, Bharat B. ; Yunus, Furhan ; Samant, Sandeep ; Raez, Luis E. ; Mehra, Ranee ; Kumar, Priya ; Ondrey, Frank ; Marchand, Patrice ; Braegas, Bettina ; Seiwert, Tanguy Y. ; Villaflor, Victoria M. ; Haraf, Daniel J. ; Vokes, Everett E. / Phase III randomized trial of induction chemotherapy in patients with N2 or N3 locally advanced head and neck cancer. In: Journal of Clinical Oncology. 2014 ; Vol. 32, No. 25. pp. 2735-2743.
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title = "Phase III randomized trial of induction chemotherapy in patients with N2 or N3 locally advanced head and neck cancer",
abstract = "Purpose: 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. Patients and 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/m2 on day 1, cisplatin 75 mg/m2 on day 1, and fluorouracil 750 mg/m2 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. Conclusion: 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.",
author = "Cohen, {Ezra E.W.} and Karrison, {Theodore G.} and Masha Kocherginsky and Jeffrey Mueller and Robyn Egan and Huang, {Chao H.} and Brockstein, {Bruce E.} and Agulnik, {Mark B.} and Mittal, {Bharat B.} and Furhan Yunus and Sandeep Samant and Raez, {Luis E.} and Ranee Mehra and Priya Kumar and Frank Ondrey and Patrice Marchand and Bettina Braegas and Seiwert, {Tanguy Y.} and Villaflor, {Victoria M.} and Haraf, {Daniel J.} and Vokes, {Everett E.}",
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Cohen, EEW, Karrison, TG, Kocherginsky, M, Mueller, J, Egan, R, Huang, CH, Brockstein, BE, Agulnik, MB, Mittal, BB, Yunus, F, Samant, S, Raez, LE, Mehra, R, Kumar, P, Ondrey, F, Marchand, P, Braegas, B, Seiwert, TY, Villaflor, VM, Haraf, DJ & Vokes, EE 2014, 'Phase III randomized trial of induction chemotherapy in patients with N2 or N3 locally advanced head and neck cancer', Journal of Clinical Oncology, vol. 32, no. 25, pp. 2735-2743. https://doi.org/10.1200/JCO.2013.54.6309

Phase III randomized trial of induction chemotherapy in patients with N2 or N3 locally advanced head and neck cancer. / Cohen, Ezra E.W.; Karrison, Theodore G.; Kocherginsky, Masha; Mueller, Jeffrey; Egan, Robyn; Huang, Chao H.; Brockstein, Bruce E.; Agulnik, Mark B.; Mittal, Bharat B.; Yunus, Furhan; Samant, Sandeep; Raez, Luis E.; Mehra, Ranee; Kumar, Priya; Ondrey, Frank; Marchand, Patrice; Braegas, Bettina; Seiwert, Tanguy Y.; Villaflor, Victoria M.; Haraf, Daniel J.; Vokes, Everett E.

In: Journal of Clinical Oncology, Vol. 32, No. 25, 01.09.2014, p. 2735-2743.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Phase III randomized trial of induction chemotherapy in patients with N2 or N3 locally advanced head and neck cancer

AU - Cohen, Ezra E.W.

AU - Karrison, Theodore G.

AU - Kocherginsky, Masha

AU - Mueller, Jeffrey

AU - Egan, Robyn

AU - Huang, Chao H.

AU - Brockstein, Bruce E.

AU - Agulnik, Mark B.

AU - Mittal, Bharat B.

AU - Yunus, Furhan

AU - Samant, Sandeep

AU - Raez, Luis E.

AU - Mehra, Ranee

AU - Kumar, Priya

AU - Ondrey, Frank

AU - Marchand, Patrice

AU - Braegas, Bettina

AU - Seiwert, Tanguy Y.

AU - Villaflor, Victoria M.

AU - Haraf, Daniel J.

AU - Vokes, Everett E.

PY - 2014/9/1

Y1 - 2014/9/1

N2 - Purpose: 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. Patients and 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/m2 on day 1, cisplatin 75 mg/m2 on day 1, and fluorouracil 750 mg/m2 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. Conclusion: 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.

AB - Purpose: 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. Patients and 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/m2 on day 1, cisplatin 75 mg/m2 on day 1, and fluorouracil 750 mg/m2 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. Conclusion: 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.

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DO - 10.1200/JCO.2013.54.6309

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JO - Journal of Clinical Oncology

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