PMID- 18784101
OWN - NLM
STAT- MEDLINE
DCOM- 20080916
LR  - 20220420
IS  - 1533-4406 (Electronic)
IS  - 0028-4793 (Linking)
VI  - 359
IP  - 11
DP  - 2008 Sep 11
TI  - Platinum-based chemotherapy plus cetuximab in head and neck cancer.
PG  - 1116-27
LID - 10.1056/NEJMoa0802656 [doi]
AB  - BACKGROUND: Cetuximab is effective in platinum-resistant recurrent or metastatic 
      squamous-cell carcinoma of the head and neck. We investigated the efficacy of 
      cetuximab plus platinum-based chemotherapy as first-line treatment in patients 
      with recurrent or metastatic squamous-cell carcinoma of the head and neck. 
      METHODS: We randomly assigned 220 of 442 eligible patients with untreated 
      recurrent or metastatic squamous-cell carcinoma of the head and neck to receive 
      cisplatin (at a dose of 100 mg per square meter of body-surface area on day 1) or 
      carboplatin (at an area under the curve of 5 mg per milliliter per minute, as a 
      1-hour intravenous infusion on day 1) plus fluorouracil (at a dose of 1000 mg per 
      square meter per day for 4 days) every 3 weeks for a maximum of 6 cycles and 222 
      patients to receive the same chemotherapy plus cetuximab (at a dose of 400 mg per 
      square meter initially, as a 2-hour intravenous infusion, then 250 mg per square 
      meter, as a 1-hour intravenous infusion per week) for a maximum of 6 cycles. 
      Patients with stable disease who received chemotherapy plus cetuximab continued 
      to receive cetuximab until disease progression or unacceptable toxic effects, 
      whichever occurred first. RESULTS: Adding cetuximab to platinum-based 
      chemotherapy with fluorouracil (platinum-fluorouracil) significantly prolonged 
      the median overall survival from 7.4 months in the chemotherapy-alone group to 
      10.1 months in the group that received chemotherapy plus cetuximab (hazard ratio 
      for death, 0.80; 95% confidence interval, 0.64 to 0.99; P=0.04). The addition of 
      cetuximab prolonged the median progression-free survival time from 3.3 to 5.6 
      months (hazard ratio for progression, 0.54; P<0.001) and increased the response 
      rate from 20% to 36% (P<0.001). The most common grade 3 or 4 adverse events in 
      the chemotherapy-alone and cetuximab groups were anemia (19% and 13%, 
      respectively), neutropenia (23% and 22%), and thrombocytopenia (11% in both 
      groups). Sepsis occurred in 9 patients in the cetuximab group and in 1 patient in 
      the chemotherapy-alone group (P=0.02). Of 219 patients receiving cetuximab, 9% 
      had grade 3 skin reactions and 3% had grade 3 or 4 infusion-related reactions. 
      There were no cetuximab-related deaths. CONCLUSIONS: As compared with 
      platinum-based chemotherapy plus fluorouracil alone, cetuximab plus 
      platinum-fluorouracil chemotherapy improved overall survival when given as 
      first-line treatment in patients with recurrent or metastatic squamous-cell 
      carcinoma of the head and neck. (ClinicalTrials.gov number, NCT00122460.)
CI  - 2008 Massachusetts Medical Society
FAU - Vermorken, Jan B
AU  - Vermorken JB
AD  - Antwerp University Hospital, Department of Medical Oncology, Edegem, Belgium. 
      jan.b.vermorken@uza.be
FAU - Mesia, Ricard
AU  - Mesia R
FAU - Rivera, Fernando
AU  - Rivera F
FAU - Remenar, Eva
AU  - Remenar E
FAU - Kawecki, Andrzej
AU  - Kawecki A
FAU - Rottey, Sylvie
AU  - Rottey S
FAU - Erfan, Jozsef
AU  - Erfan J
FAU - Zabolotnyy, Dmytro
AU  - Zabolotnyy D
FAU - Kienzer, Heinz-Roland
AU  - Kienzer HR
FAU - Cupissol, Didier
AU  - Cupissol D
FAU - Peyrade, Frederic
AU  - Peyrade F
FAU - Benasso, Marco
AU  - Benasso M
FAU - Vynnychenko, Ihor
AU  - Vynnychenko I
FAU - De Raucourt, Dominique
AU  - De Raucourt D
FAU - Bokemeyer, Carsten
AU  - Bokemeyer C
FAU - Schueler, Armin
AU  - Schueler A
FAU - Amellal, Nadia
AU  - Amellal N
FAU - Hitt, Ricardo
AU  - Hitt R
LA  - eng
SI  - ClinicalTrials.gov/NCT00122460
PT  - Clinical Trial, Phase III
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - N Engl J Med
JT  - The New England journal of medicine
JID - 0255562
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - BG3F62OND5 (Carboplatin)
RN  - PQX0D8J21J (Cetuximab)
RN  - Q20Q21Q62J (Cisplatin)
RN  - U3P01618RT (Fluorouracil)
SB  - IM
CIN - N Engl J Med. 2008 Dec 18;359(25):2725; author reply 2726. PMID: 19092159
CIN - N Engl J Med. 2008 Dec 18;359(25):2725-6; author reply 2726. PMID: 19102011
CIN - Nat Clin Pract Oncol. 2009 Mar;6(3):132-3. PMID: 19190590
MH  - Aged
MH  - Anemia/chemically induced
MH  - Antibodies, Monoclonal/*administration & dosage/adverse effects
MH  - Antibodies, Monoclonal, Humanized
MH  - Antineoplastic Combined Chemotherapy Protocols/adverse effects/*therapeutic use
MH  - Carboplatin/administration & dosage
MH  - Carcinoma, Squamous Cell/*drug therapy/mortality/secondary
MH  - Cetuximab
MH  - Cisplatin/administration & dosage
MH  - Disease Progression
MH  - Female
MH  - Fluorouracil/administration & dosage
MH  - Head and Neck Neoplasms/*drug therapy/mortality
MH  - Humans
MH  - Kaplan-Meier Estimate
MH  - Male
MH  - Middle Aged
MH  - Neoplasm Recurrence, Local/drug therapy
MH  - Neutropenia/chemically induced
MH  - Thrombocytopenia/chemically induced
EDAT- 2008/09/12 09:00
MHDA- 2008/09/17 09:00
CRDT- 2008/09/12 09:00
PHST- 2008/09/12 09:00 [pubmed]
PHST- 2008/09/17 09:00 [medline]
PHST- 2008/09/12 09:00 [entrez]
AID - 359/11/1116 [pii]
AID - 10.1056/NEJMoa0802656 [doi]
PST - ppublish
SO  - N Engl J Med. 2008 Sep 11;359(11):1116-27. doi: 10.1056/NEJMoa0802656.