Cetuximab (Erbitux) in Combination With Cisplatin or Carboplatin and 5-Fluorouracil in the First Line Treatment of Subjects With Recurrent and/or Metastatic Squamous Cell Carcinoma of the Head and Neck (EXTREME)

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ClinicalTrials.gov Identifier: NCT00122460

Recruitment Status : Completed

First Posted : July 22, 2005

Results First Posted : September 30, 2011

Last Update Posted : July 23, 2014

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Sponsor:

Information provided by (Responsible Party):

Merck KGaA, Darmstadt, Germany

Study Type	Interventional
Study Design	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Condition	Head and Neck Cancer
Interventions	Drug: Cetuximab + Platinum (Cisplatin or Carboplatin) + 5Fluorouracil (5-FU) Drug: Platinum (Cisplatin or Carboplatin) + 5-FU
Enrollment	442

Participant Flow

Recruitment Details	First/last subject(informed consent): 14Dec 2004/28 Dec2005. Clinical cut-off: 12 Mar 2007. 80 centers in Europe: Austria (3), Belgium (5), Czech Republic (2), France (12),Germany (8), Hungary (4), Italy (5), Netherlands (4), Poland (5), Portugal (3), Russia (4), Slovakia (2), Spain (9), Sweden (3), Switzerland (3), UK (4), and Ukraine (4).
Pre-assignment Details	477 subjects screened. 41 ineligible for treatment at end of screening (inclusion/exclusion criteria not fulfilled (30),death (3),consent withdrawal(3), symptomatic deterioration(2),non-compliance with timelines(1),refusal to continue study procedures (1), missing (1).436 eligible for treatment; however 6 of the ineligible patients were randomized


Arm/Group Title	Cetuximab Plus Chemotherapy	Chemotherapy Alone
Arm/Group Description	Subjects in will receive initial do...	All doses will be given by IV infus...
Arm/Group Description	Subjects in will receive initial dose of 400 mg/m^2 cetuximab (over 2 hours) followed by weekly doses of 250 mg/m^2 (over 1 hour). All doses will be given by intravenous (IV) infusion. Subjects will receive either Cisplatin (100 mg/m^2 on day 1) + 5-FU (1000 mg/m^2 continuous IV from day 1 to day 4) every 3 weeks or Carboplatin (Area under the curve (AUC) 5 IV on day 1) + 5-FU (1000 mg/m^2 continuous IV from day 1 to day 4) every 3 weeks.	All doses will be given by IV infusion. Subjects will receive either Cisplatin (100 mg/m^2 on day 1) + 5-FU (1000 mg/m^2 continuous IV from day 1 to day 4) every 3 weeks or Carboplatin (AUC 5 IV on day 1) + 5-FU (1000 mg/m^2 continuous IV from day 1 to day 4) every 3 weeks.
Period Title: Overall Study
Started	222 ^[1]	220 ^[1]
Completed	215	219
Not Completed	7	1
Reason Not Completed
investigational study phase ongoing	7	1
[1] Intention To Treat population, treatment group as randomized

Baseline Characteristics

Arm/Group Title		Cetuximab Plus Chemotherapy	Chemotherapy Alone	Total
Arm/Group Description		Subjects in will receive initial do...	All doses will be given by IV infus...	Total of all reporting groups
Arm/Group Description		Subjects in will receive initial dose of 400 mg/m^2 cetuximab (over 2 hours) followed by weekly doses of 250 mg/m^2 (over 1 hour). All doses will be given by intravenous (IV) infusion. Subjects will receive either Cisplatin (100 mg/m^2 on day 1) + 5-FU (1000 mg/m^2 continuous IV from day 1 to day 4) every 3 weeks or Carboplatin (Area under the curve (AUC) 5 IV on day 1) + 5-FU (1000 mg/m^2 continuous IV from day 1 to day 4) every 3 weeks.	All doses will be given by IV infusion. Subjects will receive either Cisplatin (100 mg/m^2 on day 1) + 5-FU (1000 mg/m^2 continuous IV from day 1 to day 4) every 3 weeks or Carboplatin (AUC 5 IV on day 1) + 5-FU (1000 mg/m^2 continuous IV from day 1 to day 4) every 3 weeks.	Total of all reporting groups
Overall Number of Baseline Participants		222	220	442
Baseline Analysis Population Description		[Not Specified]
Baseline Analysis Population Description		[Not Specified]
Age, Categorical Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	222 participants	220 participants	442 participants
	<=18 years	0 0.0%	0 0.0%	0 0.0%
	Between 18 and 65 years	183 82.4%	182 82.7%	365 82.6%
	>=65 years	39 17.6%	38 17.3%	77 17.4%
Age, Continuous Mean (Standard Deviation) Unit of measure: Years
	Number Analyzed	222 participants	220 participants	442 participants
		57.1 (8.0)	56.7 (8.7)	56.9 (8.3)
Sex: Female, Male Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	222 participants	220 participants	442 participants
	Female	25 11.3%	18 8.2%	43 9.7%
	Male	197 88.7%	202 91.8%	399 90.3%
Region of Enrollment Measure Type: Number Unit of measure: Participants	Number Analyzed	222 participants	220 participants	442 participants
Portugal		3	6	9
Slovakia		3	1	4
Spain		38	41	79
Ukraine		18	16	34
Austria		4	10	14
Russian Federation		9	7	16
United Kingdom		4	5	9
Switzerland		4	4	8
Italy		14	12	26
France		45	31	76
Czech Republic		4	5	9
Hungary		19	24	43
Belgium		14	16	30
Poland		18	18	36
Germany		18	14	32
Netherlands		4	6	10
Sweden		3	4	7

Outcome Measures

1.Primary Outcome


Title	Overall Survival Time (OS)
Description	Time from randomization to death. Patients without event are censored ...
Description	Time from randomization to death. Patients without event are censored at the last date known to be alive or at the clinical cut-off date, whatever is earlier.
Time Frame	time from randomization to death or last day known to be alive, reported between day of first patient randomised, 21 Dec 2004, until cut-off date 12 Mar 2007

Outcome Measure Data

Analysis Population Description

Primary analysis on Intent to Treat (ITT) population (allocation to treatment groups as randomized).

Analysis performed after the required number of 340 deaths had been reported (expected effect: 36% increase in median survival time, power = 80%, alpha=5% (two-sided)). The Clinical cut-off date was 12 Mar 2007.


Arm/Group Title	Cetuximab Plus Chemotherapy	Chemotherapy Alone
Arm/Group Description:	Subjects in will receive initial do...	All doses will be given by IV infus...
Arm/Group Description:	Subjects in will receive initial dose of 400 mg/m^2 cetuximab (over 2 hours) followed by weekly doses of 250 mg/m^2 (over 1 hour). All doses will be given by intravenous (IV) infusion. Subjects will receive either Cisplatin (100 mg/m^2 on day 1) + 5-FU (1000 mg/m^2 continuous IV from day 1 to day 4) every 3 weeks or Carboplatin (Area under the curve (AUC) 5 IV on day 1) + 5-FU (1000 mg/m^2 continuous IV from day 1 to day 4) every 3 weeks.	All doses will be given by IV infusion. Subjects will receive either Cisplatin (100 mg/m^2 on day 1) + 5-FU (1000 mg/m^2 continuous IV from day 1 to day 4) every 3 weeks or Carboplatin (AUC 5 IV on day 1) + 5-FU (1000 mg/m^2 continuous IV from day 1 to day 4) every 3 weeks.
Overall Number of Participants Analyzed	222	220
Median (95% Confidence Interval) Unit of Measure: months
	10.1 (8.6 to 11.2)	7.4 (6.4 to 8.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Cetuximab Plus Chemotherapy, Chemotherapy Alone
	Comments	The primary analysis tested the equality of OS between treatment groups applying a 2-sided stratified log-rank test (α=5%), taking into account the strata used for randomization (previous chemotherapy (CTX) [no vs. yes] and Karnofsky Performance Status (KPS) [<80 vs. ≥80]). Median overall survival was estimated using the Kaplan-Meier method. The Hazard Ratio (HR) of cetuximab + CTX over CTX alone was calculated using the Cox proportional hazards model stratified by randomization strata.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.036
	Comments	[Not Specified]
	Method	Stratified Log Rank
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.797
	Confidence Interval	(2-Sided) 95% 0.644 to 0.986
	Estimation Comments	[Not Specified]

2.Secondary Outcome


Title	Progression-free Survival Time (PFS)
Description	Duration from randomization until radiological progression according t...
Description	Duration from randomization until radiological progression according to investigator (based on modified World Health Organisation (WHO) criteria) or death due to any cause. Only deaths within 60 days of last tumor assessment are considered. Patients without event are censored on the date of last tumor assessment.
Time Frame	time from randomization to disease progression, death or last tumor assessment, reported between day of first patient randomised, 21 Dec 2004, until cut-off date 12 Mar 2007

Outcome Measure Data

Analysis Population Description

Analysis on ITT population (allocation to treatment groups as randomized). Analysis performed at clinical cut off date, determined by primary endpoint.


Arm/Group Title	Cetuximab Plus Chemotherapy	Chemotherapy Alone
Arm/Group Description:	Subjects in will receive initial do...	All doses will be given by IV infus...
Arm/Group Description:	Subjects in will receive initial dose of 400 mg/m^2 cetuximab (over 2 hours) followed by weekly doses of 250 mg/m^2 (over 1 hour). All doses will be given by intravenous (IV) infusion. Subjects will receive either Cisplatin (100 mg/m^2 on day 1) + 5-FU (1000 mg/m^2 continuous IV from day 1 to day 4) every 3 weeks or Carboplatin (Area under the curve (AUC) 5 IV on day 1) + 5-FU (1000 mg/m^2 continuous IV from day 1 to day 4) every 3 weeks.	All doses will be given by IV infusion. Subjects will receive either Cisplatin (100 mg/m^2 on day 1) + 5-FU (1000 mg/m^2 continuous IV from day 1 to day 4) every 3 weeks or Carboplatin (AUC 5 IV on day 1) + 5-FU (1000 mg/m^2 continuous IV from day 1 to day 4) every 3 weeks.
Overall Number of Participants Analyzed	222	220
Median (95% Confidence Interval) Unit of Measure: months
	5.6 (5.0 to 6.0)	3.3 (2.9 to 4.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Cetuximab Plus Chemotherapy, Chemotherapy Alone
	Comments	To test the equality of PFS between treatment groups, a two-sided stratified log-rank test (α=5%)was used, taking into account strata used for randomization (previous CTX [yes/no] and KPS [<80 vs. ≥80]). Median PFS time was estimated using the Kaplan-Meier method. The HR of cetuximab + CTX over CTX alone was calculated using the Cox proportional hazards model stratified by randomization strata.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	[Not Specified]
	Method	Stratified Log Rank
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.538
	Confidence Interval	(2-Sided) 95% 0.431 to 0.672
	Estimation Comments	[Not Specified]

3.Secondary Outcome


Title	Best Overall Response
Description	The best overall response rate is defined as the percentage of subject...
Description	The best overall response rate is defined as the percentage of subjects having achieved confirmed Complete Response + Partial Response as the best overall response according to radiological assessments according to investigator (based on modified WHO criteria).
Time Frame	evaluations were performed every 6 weeks until progression, reported between day of first patient randomised, 21 Dec 2004, until cut-off date 12 Mar 2007

Outcome Measure Data

Analysis Population Description

Analysis on ITT population (allocation to treatment groups as randomized). Analysis performed at clinical cut off date, determined by primary endpoint.


Arm/Group Title	Cetuximab Plus Chemotherapy	Chemotherapy Alone
Arm/Group Description:	Subjects in will receive initial do...	All doses will be given by IV infus...
Arm/Group Description:	Subjects in will receive initial dose of 400 mg/m^2 cetuximab (over 2 hours) followed by weekly doses of 250 mg/m^2 (over 1 hour). All doses will be given by intravenous (IV) infusion. Subjects will receive either Cisplatin (100 mg/m^2 on day 1) + 5-FU (1000 mg/m^2 continuous IV from day 1 to day 4) every 3 weeks or Carboplatin (Area under the curve (AUC) 5 IV on day 1) + 5-FU (1000 mg/m^2 continuous IV from day 1 to day 4) every 3 weeks.	All doses will be given by IV infusion. Subjects will receive either Cisplatin (100 mg/m^2 on day 1) + 5-FU (1000 mg/m^2 continuous IV from day 1 to day 4) every 3 weeks or Carboplatin (AUC 5 IV on day 1) + 5-FU (1000 mg/m^2 continuous IV from day 1 to day 4) every 3 weeks.
Overall Number of Participants Analyzed	222	220
Measure Type: Number Number (95% Confidence Interval) Unit of Measure: percentage of participants
	35.6 (29.3 to 42.3)	19.5 (14.5 to 25.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Cetuximab Plus Chemotherapy, Chemotherapy Alone
	Comments	A Cochran-Mantel-Haenszel (CMH) test was performed using the randomization strata previous CTX (no vs. yes) and KPS (<80 vs. ≥80). Treatment group comparisons were performed two-sided with α=5%.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.0001
	Comments	[Not Specified]
	Method	Cochran-Mantel-Haenszel
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	2.326
	Confidence Interval	(2-Sided) 95% 1.504 to 3.600
	Estimation Comments	[Not Specified]

4.Secondary Outcome


Title	Disease Control
Description	The disease control rate is defined as the percentage of subjects havi...
Description	The disease control rate is defined as the percentage of subjects having achieved confirmed Complete Response + Partial Response + Stable Disease as best overall response according to radiological assessments according to investigator (based on modified WHO criteria).
Time Frame	evaluations were performed every 6 weeks until progression, reported between day of first patient randomised, 21 Dec 2004, until cut-off date 12 Mar 2007

Outcome Measure Data

Analysis Population Description

Analysis on ITT population (allocation to treatment groups as randomized). Analysis performed at clinical cut off date, determined by primary endpoint.


Arm/Group Title	Cetuximab Plus Chemotherapy	Chemotherapy Alone
Arm/Group Description:	Subjects in will receive initial do...	All doses will be given by IV infus...
Arm/Group Description:	Subjects in will receive initial dose of 400 mg/m^2 cetuximab (over 2 hours) followed by weekly doses of 250 mg/m^2 (over 1 hour). All doses will be given by intravenous (IV) infusion. Subjects will receive either Cisplatin (100 mg/m^2 on day 1) + 5-FU (1000 mg/m^2 continuous IV from day 1 to day 4) every 3 weeks or Carboplatin (Area under the curve (AUC) 5 IV on day 1) + 5-FU (1000 mg/m^2 continuous IV from day 1 to day 4) every 3 weeks.	All doses will be given by IV infusion. Subjects will receive either Cisplatin (100 mg/m^2 on day 1) + 5-FU (1000 mg/m^2 continuous IV from day 1 to day 4) every 3 weeks or Carboplatin (AUC 5 IV on day 1) + 5-FU (1000 mg/m^2 continuous IV from day 1 to day 4) every 3 weeks.
Overall Number of Participants Analyzed	222	220
Measure Type: Number Number (95% Confidence Interval) Unit of Measure: percentage of participants
	81.1 (75.3 to 86.0)	60.0 (53.2 to 66.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Cetuximab Plus Chemotherapy, Chemotherapy Alone
	Comments	A Cochran-Mantel-Haenszel (CMH) test was performed using the randomization strata previous CTX (no vs. yes) and KPS (<80 vs. ≥80). Treatment group comparisons were performed two-sided with α=5%.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	[Not Specified]
	Method	Cochran-Mantel-Haenszel
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	2.881
	Confidence Interval	(2-Sided) 95% 1.870 to 4.441
	Estimation Comments	[Not Specified]

5.Secondary Outcome


Title	Time to Treatment Failure
Description	Time from randomization to date of the first occurrence of; progressio...
Description	Time from randomization to date of the first occurrence of; progression, discontinuation of treatment due to progression or adverse event, start of new anticancer therapy, withdrawal of consent, or death (within 60 days of last tumor assessment). Patients without event are censored on the date of last tumor assessment.
Time Frame	Time from randomization to treatment failure or last tumor assessment, reported between day of first patient randomised, 21 Dec 2004, until cut-off date 12 Mar 2007

Outcome Measure Data

Analysis Population Description

Analysis on ITT population (allocation to treatment groups as randomized). Analysis performed at clinical cut off date, determined by primary endpoint.


Arm/Group Title	Cetuximab Plus Chemotherapy	Chemotherapy Alone
Arm/Group Description:	Subjects in will receive initial do...	All doses will be given by IV infus...
Arm/Group Description:	Subjects in will receive initial dose of 400 mg/m^2 cetuximab (over 2 hours) followed by weekly doses of 250 mg/m^2 (over 1 hour). All doses will be given by intravenous (IV) infusion. Subjects will receive either Cisplatin (100 mg/m^2 on day 1) + 5-FU (1000 mg/m^2 continuous IV from day 1 to day 4) every 3 weeks or Carboplatin (Area under the curve (AUC) 5 IV on day 1) + 5-FU (1000 mg/m^2 continuous IV from day 1 to day 4) every 3 weeks.	All doses will be given by IV infusion. Subjects will receive either Cisplatin (100 mg/m^2 on day 1) + 5-FU (1000 mg/m^2 continuous IV from day 1 to day 4) every 3 weeks or Carboplatin (AUC 5 IV on day 1) + 5-FU (1000 mg/m^2 continuous IV from day 1 to day 4) every 3 weeks.
Overall Number of Participants Analyzed	222	220
Median (95% Confidence Interval) Unit of Measure: months
	4.8 (4.0 to 5.6)	3.0 (2.8 to 3.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Cetuximab Plus Chemotherapy, Chemotherapy Alone
	Comments	Treatment groups were compared applying a two-sided stratified log-rank test (α=5%), taking into account strata used for randomization (previous CTX [yes/no] and KPS [<80 vs. ≥80]). Median time to treatment failure was estimated using the Kaplan-Meier method. The HR of cetuximab + CTX over CTX alone was calculated using the Cox proportional hazards model stratified by randomization strata.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	[Not Specified]
	Method	Stratified Log Rank
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.593
	Confidence Interval	(2-Sided) 95% 0.484 to 0.727
	Estimation Comments	[Not Specified]

6.Secondary Outcome


Title	Duration of Response
Description	Time from first assessment of Complete Response or Partial Response to...
Description	Time from first assessment of Complete Response or Partial Response to disease progression or death (within 60 days of last tumor assessment). Patients without event are censored on the date of last tumor assessment. Tumor assessments based on modified WHO criteria.
Time Frame	time from first assessment of Complete Response or Partial Response to disease progression, death or last tumor assessment, reported between day of first patient randomised, 21 Dec 2004, until cut-off date 12 Mar 2007

Outcome Measure Data

Analysis Population Description

Analysis on ITT population (allocation to treatment groups as randomized). Analysis performed at clinical cut off date, determined by primary endpoint.


Arm/Group Title	Cetuximab Plus Chemotherapy	Chemotherapy Alone
Arm/Group Description:	Subjects in will receive initial do...	All doses will be given by IV infus...
Arm/Group Description:	Subjects in will receive initial dose of 400 mg/m^2 cetuximab (over 2 hours) followed by weekly doses of 250 mg/m^2 (over 1 hour). All doses will be given by intravenous (IV) infusion. Subjects will receive either Cisplatin (100 mg/m^2 on day 1) + 5-FU (1000 mg/m^2 continuous IV from day 1 to day 4) every 3 weeks or Carboplatin (Area under the curve (AUC) 5 IV on day 1) + 5-FU (1000 mg/m^2 continuous IV from day 1 to day 4) every 3 weeks.	All doses will be given by IV infusion. Subjects will receive either Cisplatin (100 mg/m^2 on day 1) + 5-FU (1000 mg/m^2 continuous IV from day 1 to day 4) every 3 weeks or Carboplatin (AUC 5 IV on day 1) + 5-FU (1000 mg/m^2 continuous IV from day 1 to day 4) every 3 weeks.
Overall Number of Participants Analyzed	222	220
Median (95% Confidence Interval) Unit of Measure: months
	5.6 (4.7 to 6.0)	4.7 (3.5 to 5.9)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Cetuximab Plus Chemotherapy, Chemotherapy Alone
	Comments	To test the equality of duration of response between treatment groups, the two-sided stratified log-rank test (α=5%) was used taking strata used for randomization into account (previous CTX [no vs. yes] and KPS [<80 vs. ≥80]). Median duration of response was estimated using the Kaplan-Meier method. The HR of cetuximab + CTX over CTX alone was calculated using the Cox proportional hazards model stratified by randomization strata.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.21
	Comments	[Not Specified]
	Method	Stratified Log Rank
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.762
	Confidence Interval	(2-Sided) 95% 0.497 to 1.168
	Estimation Comments	[Not Specified]

7.Secondary Outcome


Title	Quality of Life (QOL) Assessment European Organisation for the Research and Treatment of Cancer (EORTC) QLQ-C30 Global Health Status
Description	Mean global health status scores (EORTC QLQ-C30) against time for each...
Description	Mean global health status scores (EORTC QLQ-C30) against time for each treatment group. Scores were derived from mutually exclusive sets of items, with scale scores ranging from 0 to 100 after a linear transformation. Higher scores indicate a better QoL.
Time Frame	at baseline, day 1 of cycle 3, first 6-weekly evaluation following completion of chemotherapy, 6 & 12 months after randomization, reported between day of first patient randomised, 21 Dec 2004,until cut-off date, 12 Mar 2007

Outcome Measure Data

Analysis Population Description

Of 361 ITT subjects from countries with EORTC QLQ-C30 available, 291 completed ≥1 evaluable questionnaire. Only time points where ≥ 20% of patients completing a baseline questionnaire remained in the population were analysed. Numbers at each timepoint were (cetuximab+chemotherapy/chemotherapy alone): Baseline: 121/106; Cycle3:87/67; Month6:48/22


Arm/Group Title	Cetuximab Plus Chemotherapy	Chemotherapy Alone
Arm/Group Description:	Subjects in will receive initial do...	All doses will be given by IV infus...
Arm/Group Description:	Subjects in will receive initial dose of 400 mg/m^2 cetuximab (over 2 hours) followed by weekly doses of 250 mg/m^2 (over 1 hour). All doses will be given by intravenous (IV) infusion. Subjects will receive either Cisplatin (100 mg/m^2 on day 1) + 5-FU (1000 mg/m^2 continuous IV from day 1 to day 4) every 3 weeks or Carboplatin (Area under the curve (AUC) 5 IV on day 1) + 5-FU (1000 mg/m^2 continuous IV from day 1 to day 4) every 3 weeks.	All doses will be given by IV infusion. Subjects will receive either Cisplatin (100 mg/m^2 on day 1) + 5-FU (1000 mg/m^2 continuous IV from day 1 to day 4) every 3 weeks or Carboplatin (AUC 5 IV on day 1) + 5-FU (1000 mg/m^2 continuous IV from day 1 to day 4) every 3 weeks.
Overall Number of Participants Analyzed	152	139
Least Squares Mean (Standard Error) Unit of Measure: scores on a scale
At baseline	50.74 (3.519)	45.15 (3.745)
At cycle 3	52.68 (3.724)	45.48 (4.153)
Month 6	55.30 (4.282)	42.49 (5.959)

8.Secondary Outcome


Title	Quality of Life Assessment (EORTC QLQ-C30) Social Functioning
Description	Mean social functioning scores (EORTC QLQ-C30) against time for each t...
Description	Mean social functioning scores (EORTC QLQ-C30) against time for each treatment group. Scores were derived from mutually exclusive sets of items, with scale scores ranging from 0 to 100 after a linear transformation. Higher scores indicate a higher level of social functioning.
Time Frame	at baseline, day 1 of cycle 3, first 6-weekly evaluation following completion of chemotherapy, 6 & 12 months after randomization, reported between day of first patient randomised, 21 Dec 2004,until cut-off date, 12 Mar 2007

Outcome Measure Data

Analysis Population Description

Of 361 ITT subjects from countries with EORTC QLQ-C30 available, 291 completed ≥1 evaluable questionnaire. Only time points where ≥ 20% of patients completing a baseline questionnaire remained in the population were analysed. Numbers at each timepoint were (cetuximab +chemotherapy/chemotherapy alone): Baseline:123/109; Cycle3:87/69; Month6:48/23


Arm/Group Title	Cetuximab Plus Chemotherapy	Chemotherapy Alone
Arm/Group Description:	Subjects in will receive initial do...	All doses will be given by IV infus...
Arm/Group Description:	Subjects in will receive initial dose of 400 mg/m^2 cetuximab (over 2 hours) followed by weekly doses of 250 mg/m^2 (over 1 hour). All doses will be given by intravenous (IV) infusion. Subjects will receive either Cisplatin (100 mg/m^2 on day 1) + 5-FU (1000 mg/m^2 continuous IV from day 1 to day 4) every 3 weeks or Carboplatin (Area under the curve (AUC) 5 IV on day 1) + 5-FU (1000 mg/m^2 continuous IV from day 1 to day 4) every 3 weeks.	All doses will be given by IV infusion. Subjects will receive either Cisplatin (100 mg/m^2 on day 1) + 5-FU (1000 mg/m^2 continuous IV from day 1 to day 4) every 3 weeks or Carboplatin (AUC 5 IV on day 1) + 5-FU (1000 mg/m^2 continuous IV from day 1 to day 4) every 3 weeks.
Overall Number of Participants Analyzed	152	139
Least Squares Mean (Standard Error) Unit of Measure: scores on a scale
At baseline	62.14 (4.459)	62.05 (4.730)
At cycle 3	64.64 (4.663)	60.67 (5.176)
Month 6	61.27 (5.347)	65.72 (7.122)

9.Secondary Outcome


Title	Safety - Number of Patients Experiencing Any Adverse Event
Description	Please refer to Adverse Events section for further details
Description	Please refer to Adverse Events section for further details
Time Frame	time from first dose up to 30 after last dose of study treatment, reported between day of first dose of study treatment, 22 Dec 2004, until cut-off date 12 Mar 2007

Outcome Measure Data

Analysis Population Description

Safety population


Arm/Group Title	Cetuximab Plus Chemotherapy	Chemotherapy Alone
Arm/Group Description:	Subjects in will receive initial do...	All doses will be given by IV infus...
Arm/Group Description:	Subjects in will receive initial dose of 400 mg/m^2 cetuximab (over 2 hours) followed by weekly doses of 250 mg/m^2 (over 1 hour). All doses will be given by intravenous (IV) infusion. Subjects will receive either Cisplatin (100 mg/m^2 on day 1) + 5-FU (1000 mg/m^2 continuous IV from day 1 to day 4) every 3 weeks or Carboplatin (Area under the curve (AUC) 5 IV on day 1) + 5-FU (1000 mg/m^2 continuous IV from day 1 to day 4) every 3 weeks.	All doses will be given by IV infusion. Subjects will receive either Cisplatin (100 mg/m^2 on day 1) + 5-FU (1000 mg/m^2 continuous IV from day 1 to day 4) every 3 weeks or Carboplatin (AUC 5 IV on day 1) + 5-FU (1000 mg/m^2 continuous IV from day 1 to day 4) every 3 weeks.
Overall Number of Participants Analyzed	219	215
Measure Type: Number Unit of Measure: participants
	218	208

Adverse Events

Time Frame	Time from first dose up to 30 days after the last dose of study treatment.
Adverse Event Reporting Description	Treatment-emergent adverse events were defined as those with onset occurring at or after the first dosing day of study medication and up to 30 days after the last administration of any study drug or the clinical cut-off date.

Arm/Group Title	Cetuximab Plus Chemotherapy	Chemotherapy Alone
Arm/Group Description	Subjects in will receive initial do...	All doses will be given by IV infus...
Arm/Group Description	Subjects in will receive initial dose of 400 mg/m^2 cetuximab (over 2 hours) followed by weekly doses of 250 mg/m^2 (over 1 hour). All doses will be given by intravenous (IV) infusion. Subjects will receive either Cisplatin (100 mg/m^2 on day 1) + 5-FU (1000 mg/m^2 continuous IV from day 1 to day 4) every 3 weeks or Carboplatin (Area under the curve (AUC) 5 IV on day 1) + 5-FU (1000 mg/m^2 continuous IV from day 1 to day 4) every 3 weeks.	All doses will be given by IV infusion. Subjects will receive either Cisplatin (100 mg/m^2 on day 1) + 5-FU (1000 mg/m^2 continuous IV from day 1 to day 4) every 3 weeks or Carboplatin (AUC 5 IV on day 1) + 5-FU (1000 mg/m^2 continuous IV from day 1 to day 4) every 3 weeks.
All-Cause Mortality
	Cetuximab Plus Chemotherapy	Chemotherapy Alone
	Affected / at Risk (%)	Affected / at Risk (%)
Total	--/--	--/--
Serious Adverse Events Serious Adverse Events
	Cetuximab Plus Chemotherapy	Chemotherapy Alone
	Affected / at Risk (%)	Affected / at Risk (%)
Total	110/219 (50.23%)	102/215 (47.44%)
Blood and lymphatic system disorders
Anaemia ^† 1	5/219 (2.28%)	10/215 (4.65%)
Coagulopathy ^† 1	1/219 (0.46%)	0/215 (0.00%)
Febrile bone marrow aplasia ^† 1	1/219 (0.46%)	1/215 (0.47%)
Febrile neutropenia ^† 1	8/219 (3.65%)	9/215 (4.19%)
Haemolysis ^† 1	0/219 (0.00%)	1/215 (0.47%)
Leukocytosis ^† 1	0/219 (0.00%)	1/215 (0.47%)
Leukopenia ^† 1	1/219 (0.46%)	5/215 (2.33%)
Lymph node pain ^† 1	1/219 (0.46%)	0/215 (0.00%)
Neutropenia ^† 1	3/219 (1.37%)	10/215 (4.65%)
Pancytopenia ^† 1	1/219 (0.46%)	0/215 (0.00%)
Thrombocytopenia ^† 1	4/219 (1.83%)	6/215 (2.79%)
Cardiac disorders
Acute coronary syndrome ^† 1	1/219 (0.46%)	0/215 (0.00%)
Acute myocardial infarction ^† 1	2/219 (0.91%)	0/215 (0.00%)
Angina pectoris ^† 1	0/219 (0.00%)	1/215 (0.47%)
Angina unstable ^† 1	1/219 (0.46%)	0/215 (0.00%)
Arrhythmia ^† 1	1/219 (0.46%)	1/215 (0.47%)
Arrhythmia supraventricular ^† 1	0/219 (0.00%)	1/215 (0.47%)
Atrial fibrillation ^† 1	0/219 (0.00%)	1/215 (0.47%)
Cardiac arrest ^† 1	0/219 (0.00%)	2/215 (0.93%)
Cardiac failure ^† 1	2/219 (0.91%)	1/215 (0.47%)
Cardio-respiratory arrest ^† 1	0/219 (0.00%)	1/215 (0.47%)
Cardiopulmonary failure ^† 1	2/219 (0.91%)	0/215 (0.00%)
Coronary artery thrombosis ^† 1	0/219 (0.00%)	1/215 (0.47%)
Myocardial infarction ^† 1	2/219 (0.91%)	0/215 (0.00%)
Congenital, familial and genetic disorders
Tracheo-oesophageal fistula ^† 1	0/219 (0.00%)	1/215 (0.47%)
Eye disorders
Keratitis ^† 1	1/219 (0.46%)	0/215 (0.00%)
Gastrointestinal disorders
Abdominal pain ^† 1	2/219 (0.91%)	2/215 (0.93%)
Abdominal pain upper ^† 1	1/219 (0.46%)	2/215 (0.93%)
Aphagia ^† 1	0/219 (0.00%)	1/215 (0.47%)
Colitis ^† 1	1/219 (0.46%)	0/215 (0.00%)
Constipation ^† 1	0/219 (0.00%)	1/215 (0.47%)
Diarrhoea ^† 1	4/219 (1.83%)	2/215 (0.93%)
Duodenal ulcer perforation ^† 1	0/219 (0.00%)	1/215 (0.47%)
Dysphagia ^† 1	2/219 (0.91%)	2/215 (0.93%)
Gastrointestinal haemorrhage ^† 1	0/219 (0.00%)	1/215 (0.47%)
Haematemesis ^† 1	1/219 (0.46%)	1/215 (0.47%)
Ileus ^† 1	0/219 (0.00%)	1/215 (0.47%)
Melaena ^† 1	0/219 (0.00%)	1/215 (0.47%)
Nausea ^† 1	0/219 (0.00%)	1/215 (0.47%)
Oral pain ^† 1	1/219 (0.46%)	0/215 (0.00%)
Rectal haemorrhage ^† 1	0/219 (0.00%)	1/215 (0.47%)
Stomatitis ^† 1	2/219 (0.91%)	0/215 (0.00%)
Stress ulcer ^† 1	0/219 (0.00%)	1/215 (0.47%)
Subileus ^† 1	0/219 (0.00%)	1/215 (0.47%)
Upper gastrointestinal haemorrhage ^† 1	1/219 (0.46%)	1/215 (0.47%)
Vomiting ^† 1	5/219 (2.28%)	4/215 (1.86%)
General disorders
Asthenia ^† 1	2/219 (0.91%)	1/215 (0.47%)
Chest pain ^† 1	0/219 (0.00%)	1/215 (0.47%)
Chills ^† 1	0/219 (0.00%)	1/215 (0.47%)
Death ^† 1	1/219 (0.46%)	1/215 (0.47%)
Face oedema ^† 1	0/219 (0.00%)	1/215 (0.47%)
Fatigue ^† 1	4/219 (1.83%)	2/215 (0.93%)
General physical health deterioration ^† 1	5/219 (2.28%)	2/215 (0.93%)
Hyperthermia ^† 1	0/219 (0.00%)	1/215 (0.47%)
Mucosal inflammation ^† 1	5/219 (2.28%)	6/215 (2.79%)
Multi-organ failure ^† 1	1/219 (0.46%)	0/215 (0.00%)
Oedema ^† 1	1/219 (0.46%)	0/215 (0.00%)
Oedema peripheral ^† 1	1/219 (0.46%)	0/215 (0.00%)
Performance status decreased ^† 1	2/219 (0.91%)	4/215 (1.86%)
Pyrexia ^† 1	2/219 (0.91%)	7/215 (3.26%)
Sudden death ^† 1	2/219 (0.91%)	0/215 (0.00%)
Hepatobiliary disorders
Hepatomegaly ^† 1	0/219 (0.00%)	1/215 (0.47%)
Hyperbilirubinaemia ^† 1	1/219 (0.46%)	0/215 (0.00%)
Immune system disorders
Anaphylactic reaction ^† 1	1/219 (0.46%)	0/215 (0.00%)
Hypersensitivity ^† 1	4/219 (1.83%)	0/215 (0.00%)
Infections and infestations
Abscess neck ^† 1	1/219 (0.46%)	0/215 (0.00%)
Bronchopneumonia ^† 1	1/219 (0.46%)	1/215 (0.47%)
Catheter related infection ^† 1	2/219 (0.91%)	0/215 (0.00%)
Catheter sepsis ^† 1	1/219 (0.46%)	0/215 (0.00%)
Central line infection ^† 1	1/219 (0.46%)	0/215 (0.00%)
Erysipelas ^† 1	1/219 (0.46%)	0/215 (0.00%)
Gastroenteritis ^† 1	1/219 (0.46%)	0/215 (0.00%)
Infection ^† 1	2/219 (0.91%)	2/215 (0.93%)
Lower respiratory tract infection ^† 1	0/219 (0.00%)	1/215 (0.47%)
Lung infection ^† 1	0/219 (0.00%)	1/215 (0.47%)
Lymph gland infection ^† 1	1/219 (0.46%)	0/215 (0.00%)
Meningitis ^† 1	1/219 (0.46%)	0/215 (0.00%)
Neutropenic sepsis ^† 1	0/219 (0.00%)	1/215 (0.47%)
Pharyngitis ^† 1	1/219 (0.46%)	0/215 (0.00%)
Pneumococcal sepsis ^† 1	1/219 (0.46%)	0/215 (0.00%)
Pneumonia ^† 1	10/219 (4.57%)	4/215 (1.86%)
Pneumonia staphylococcal ^† 1	0/219 (0.00%)	1/215 (0.47%)
Pulmonary tuberculosis ^† 1	1/219 (0.46%)	0/215 (0.00%)
Pyothorax ^† 1	1/219 (0.46%)	0/215 (0.00%)
Respiratory tract infection ^† 1	0/219 (0.00%)	2/215 (0.93%)
Salmonella sepsis ^† 1	1/219 (0.46%)	0/215 (0.00%)
Sepsis ^† 1	6/219 (2.74%)	1/215 (0.47%)
Septic shock ^† 1	3/219 (1.37%)	0/215 (0.00%)
Staphylococcal infection ^† 1	1/219 (0.46%)	0/215 (0.00%)
Thrombophlebitis septic ^† 1	0/219 (0.00%)	1/215 (0.47%)
Injury, poisoning and procedural complications
Feeding tube complication ^† 1	1/219 (0.46%)	0/215 (0.00%)
Gastrostomy failure ^† 1	0/219 (0.00%)	1/215 (0.47%)
Hip fracture ^† 1	0/219 (0.00%)	1/215 (0.47%)
Post procedural haemorrhage ^† 1	2/219 (0.91%)	1/215 (0.47%)
Investigations
Blood creatinine increased ^† 1	1/219 (0.46%)	1/215 (0.47%)
Creatinine renal clearance decreased ^† 1	1/219 (0.46%)	0/215 (0.00%)
Haemoglobin ^† 1	0/219 (0.00%)	1/215 (0.47%)
Haemoglobin decreased ^† 1	0/219 (0.00%)	4/215 (1.86%)
Neurological examination abnormal ^† 1	0/219 (0.00%)	1/215 (0.47%)
Oxygen saturation decreased ^† 1	0/219 (0.00%)	1/215 (0.47%)
Platelet count decreased ^† 1	1/219 (0.46%)	0/215 (0.00%)
Transaminases increased ^† 1	1/219 (0.46%)	0/215 (0.00%)
Urine electrolytes decreased ^† 1	1/219 (0.46%)	0/215 (0.00%)
Weight decreased ^† 1	1/219 (0.46%)	3/215 (1.40%)
Metabolism and nutrition disorders
Anorexia ^† 1	3/219 (1.37%)	0/215 (0.00%)
Cachexia ^† 1	0/219 (0.00%)	1/215 (0.47%)
Dehydration ^† 1	9/219 (4.11%)	3/215 (1.40%)
Diabetes mellitus ^† 1	1/219 (0.46%)	0/215 (0.00%)
Hypercalcaemia ^† 1	2/219 (0.91%)	1/215 (0.47%)
Hyperglycaemia ^† 1	1/219 (0.46%)	3/215 (1.40%)
Hypernatraemia ^† 1	0/219 (0.00%)	1/215 (0.47%)
Hyperuricaemia ^† 1	0/219 (0.00%)	1/215 (0.47%)
Hypoalbuminaemia ^† 1	0/219 (0.00%)	1/215 (0.47%)
Hypocalcaemia ^† 1	4/219 (1.83%)	0/215 (0.00%)
Hypokalaemia ^† 1	1/219 (0.46%)	0/215 (0.00%)
Hypomagnesaemia ^† 1	4/219 (1.83%)	0/215 (0.00%)
Hyponatraemia ^† 1	2/219 (0.91%)	1/215 (0.47%)
Hypophosphataemia ^† 1	1/219 (0.46%)	0/215 (0.00%)
Hypovolaemia ^† 1	0/219 (0.00%)	1/215 (0.47%)
Malnutrition ^† 1	0/219 (0.00%)	1/215 (0.47%)
Musculoskeletal and connective tissue disorders
Bursitis ^† 1	1/219 (0.46%)	0/215 (0.00%)
Fistula ^† 1	0/219 (0.00%)	2/215 (0.93%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bladder cancer ^† 1	0/219 (0.00%)	1/215 (0.47%)
Infected neoplasm ^† 1	1/219 (0.46%)	1/215 (0.47%)
Malignant neoplasm progression ^† 1	0/219 (0.00%)	1/215 (0.47%)
Neoplasm progression ^† 1	1/219 (0.46%)	0/215 (0.00%)
Tumour associated fever ^† 1	0/219 (0.00%)	1/215 (0.47%)
Tumour haemorrhage ^† 1	2/219 (0.91%)	7/215 (3.26%)
Tumour pain ^† 1	1/219 (0.46%)	0/215 (0.00%)
Nervous system disorders
Brain oedema ^† 1	1/219 (0.46%)	0/215 (0.00%)
Cerebral infarction ^† 1	1/219 (0.46%)	0/215 (0.00%)
Cerebral ischaemia ^† 1	1/219 (0.46%)	1/215 (0.47%)
Coma ^† 1	0/219 (0.00%)	1/215 (0.47%)
Convulsion ^† 1	2/219 (0.91%)	3/215 (1.40%)
Dizziness ^† 1	2/219 (0.91%)	0/215 (0.00%)
Headache ^† 1	1/219 (0.46%)	0/215 (0.00%)
Intracranial hypotension ^† 1	0/219 (0.00%)	1/215 (0.47%)
Ischaemic stroke ^† 1	0/219 (0.00%)	1/215 (0.47%)
Syncope ^† 1	2/219 (0.91%)	3/215 (1.40%)
Psychiatric disorders
Confusional state ^† 1	1/219 (0.46%)	3/215 (1.40%)
Suicide attempt ^† 1	0/219 (0.00%)	1/215 (0.47%)
Renal and urinary disorders
Haematuria ^† 1	0/219 (0.00%)	1/215 (0.47%)
Renal failure ^† 1	2/219 (0.91%)	2/215 (0.93%)
Renal failure acute ^† 1	3/219 (1.37%)	3/215 (1.40%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome ^† 1	0/219 (0.00%)	1/215 (0.47%)
Bronchial obstruction ^† 1	0/219 (0.00%)	1/215 (0.47%)
Dyspnoea ^† 1	4/219 (1.83%)	11/215 (5.12%)
Dyspnoea at rest ^† 1	1/219 (0.46%)	0/215 (0.00%)
Haemoptysis ^† 1	3/219 (1.37%)	1/215 (0.47%)
Hydropneumothorax ^† 1	1/219 (0.46%)	0/215 (0.00%)
Laryngeal oedema ^† 1	0/219 (0.00%)	1/215 (0.47%)
Lung disorder ^† 1	1/219 (0.46%)	0/215 (0.00%)
Pleural effusion ^† 1	0/219 (0.00%)	1/215 (0.47%)
Pneumonia aspiration ^† 1	1/219 (0.46%)	1/215 (0.47%)
Pneumonitis ^† 1	1/219 (0.46%)	2/215 (0.93%)
Pneumothorax ^† 1	0/219 (0.00%)	2/215 (0.93%)
Productive cough ^† 1	0/219 (0.00%)	2/215 (0.93%)
Pulmonary embolism ^† 1	1/219 (0.46%)	0/215 (0.00%)
Pulmonary thrombosis ^† 1	1/219 (0.46%)	0/215 (0.00%)
Respiratory failure ^† 1	1/219 (0.46%)	5/215 (2.33%)
Stridor ^† 1	0/219 (0.00%)	1/215 (0.47%)
Skin and subcutaneous tissue disorders
Dermatitis acneiform ^† 1	1/219 (0.46%)	0/215 (0.00%)
Skin toxicity ^† 1	1/219 (0.46%)	0/215 (0.00%)
Surgical and medical procedures
Gastrostomy tube insertion ^† 1	1/219 (0.46%)	0/215 (0.00%)
Medical device removal ^† 1	1/219 (0.46%)	0/215 (0.00%)
Vascular disorders
Aortic aneurysm ^† 1	1/219 (0.46%)	0/215 (0.00%)
Aortic aneurysm rupture ^† 1	1/219 (0.46%)	0/215 (0.00%)
Deep vein thrombosis ^† 1	1/219 (0.46%)	1/215 (0.47%)
Haemorrhage ^† 1	2/219 (0.91%)	1/215 (0.47%)
Hypertension ^† 1	1/219 (0.46%)	0/215 (0.00%)
Hypotension ^† 1	2/219 (0.91%)	2/215 (0.93%)
Ischaemia ^† 1	1/219 (0.46%)	0/215 (0.00%)
Jugular vein thrombosis ^† 1	1/219 (0.46%)	0/215 (0.00%)
Peripheral ischaemia ^† 1	1/219 (0.46%)	0/215 (0.00%)
Shock ^† 1	1/219 (0.46%)	0/215 (0.00%)
Shock haemorrhagic ^† 1	1/219 (0.46%)	1/215 (0.47%)
Thrombosis ^† 1	2/219 (0.91%)	1/215 (0.47%)
Wound haemorrhage ^† 1	1/219 (0.46%)	0/215 (0.00%)
† Indicates events were collected by systematic assessment 1 Term from vocabulary, MedDRA (10.0)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Cetuximab Plus Chemotherapy	Chemotherapy Alone
	Affected / at Risk (%)	Affected / at Risk (%)
Total	214/219 (97.72%)	198/215 (92.09%)
Blood and lymphatic system disorders
Anaemia ^† 1	92/219 (42.01%)	111/215 (51.63%)
Neutropenia ^† 1	83/219 (37.90%)	77/215 (35.81%)
Thrombocytopenia ^† 1	46/219 (21.00%)	48/215 (22.33%)
Leukopenia ^† 1	41/219 (18.72%)	32/215 (14.88%)
Lymphopenia ^† 1	16/219 (7.31%)	13/215 (6.05%)
Eye disorders
Conjunctivitis ^† 1	21/219 (9.59%)	0/215 (0.00%)
Gastrointestinal disorders
Nausea ^† 1	119/219 (54.34%)	100/215 (46.51%)
Vomiting ^† 1	84/219 (38.36%)	79/215 (36.74%)
Diarrhoea ^† 1	56/219 (25.57%)	33/215 (15.35%)
Constipation ^† 1	48/219 (21.92%)	43/215 (20.00%)
Stomatitis ^† 1	31/219 (14.16%)	28/215 (13.02%)
Dysphagia ^† 1	21/219 (9.59%)	19/215 (8.84%)
Dyspepsia ^† 1	15/219 (6.85%)	7/215 (3.26%)
Abdominal pain upper ^† 1	13/219 (5.94%)	7/215 (3.26%)
General disorders
Asthenia ^† 1	56/219 (25.57%)	47/215 (21.86%)
Mucosal inflammation ^† 1	50/219 (22.83%)	38/215 (17.67%)
Fatigue ^† 1	49/219 (22.37%)	44/215 (20.47%)
Pyrexia ^† 1	48/219 (21.92%)	23/215 (10.70%)
General physical health deterioration ^† 1	11/219 (5.02%)	2/215 (0.93%)
Infections and infestations
Paronychia ^† 1	19/219 (8.68%)	0/215 (0.00%)
Investigations
Weight decreased ^† 1	41/219 (18.72%)	30/215 (13.95%)
Platelet count decreased ^† 1	13/219 (5.94%)	7/215 (3.26%)
Blood creatinine increased ^† 1	11/219 (5.02%)	13/215 (6.05%)
Haemoglobin decreased ^† 1	9/219 (4.11%)	11/215 (5.12%)
Metabolism and nutrition disorders
Anorexia ^† 1	54/219 (24.66%)	31/215 (14.42%)
Hypocalcaemia ^† 1	26/219 (11.87%)	10/215 (4.65%)
Hypokalaemia ^† 1	25/219 (11.42%)	15/215 (6.98%)
Hypomagnesaemia ^† 1	22/219 (10.05%)	11/215 (5.12%)
Hyponatraemia ^† 1	12/219 (5.48%)	17/215 (7.91%)
Hyperkalaemia ^† 1	12/219 (5.48%)	11/215 (5.12%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour pain ^† 1	19/219 (8.68%)	19/215 (8.84%)
Nervous system disorders
Headache ^† 1	20/219 (9.13%)	15/215 (6.98%)
Peripheral sensory neuropathy ^† 1	14/219 (6.39%)	8/215 (3.72%)
Dizziness ^† 1	10/219 (4.57%)	11/215 (5.12%)
Insomnia ^† 1	20/219 (9.13%)	7/215 (3.26%)
Respiratory, thoracic and mediastinal disorders
Cough ^† 1	22/219 (10.05%)	19/215 (8.84%)
Dyspnoea ^† 1	19/219 (8.68%)	19/215 (8.84%)
Productive cough ^† 1	12/219 (5.48%)	12/215 (5.58%)
Skin and subcutaneous tissue disorders
Rash ^† 1	61/219 (27.85%)	4/215 (1.86%)
Acne ^† 1	48/219 (21.92%)	0/215 (0.00%)
Dermatitis acneiform ^† 1	32/219 (14.61%)	0/215 (0.00%)
Dry skin ^† 1	30/219 (13.70%)	1/215 (0.47%)
Alopecia ^† 1	27/219 (12.33%)	15/215 (6.98%)
Pruritus ^† 1	18/219 (8.22%)	0/215 (0.00%)
Exfoliative rash ^† 1	17/219 (7.76%)	0/215 (0.00%)
Skin toxicity ^† 1	13/219 (5.94%)	0/215 (0.00%)
Vascular disorders
Hypertension ^† 1	15/219 (6.85%)	10/215 (4.65%)
Hypotension ^† 1	14/219 (6.39%)	9/215 (4.19%)
Phlebitis ^† 1	11/219 (5.02%)	5/215 (2.33%)
† Indicates events were collected by systematic assessment 1 Term from vocabulary, MedDRA (10.0)

Limitations and Caveats

Non-specific outcome measures 'Safety' & 'QOL assessments' were deleted from this entry in error.Replacement outcomes have been created. The 'Safety' outcome refers to adverse events.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

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Name/Title:	Inmaculada Ollero/Clinical Trial Manager
Organization:	Merck Serono
Phone:	+34935655433
EMail:	iollero@merck.es

Publications of Results:

Vermorken JB, Mesia R, Rivera F, Remenar E, Kawecki A, Rottey S, Erfan J, Zabolotnyy D, Kienzer HR, Cupissol D, Peyrade F, Benasso M, Vynnychenko I, De Raucourt D, Bokemeyer C, Schueler A, Amellal N, Hitt R. Platinum-based chemotherapy plus cetuximab in head and neck cancer. N Engl J Med. 2008 Sep 11;359(11):1116-27. doi: 10.1056/NEJMoa0802656.

Mesia R, Rivera F, Kawecki A, Rottey S, Hitt R, Kienzer H, Cupissol D, De Raucourt D, Benasso M, Koralewski P, Delord JP, Bokemeyer C, Curran D, Gross A, Vermorken JB. Quality of life of patients receiving platinum-based chemotherapy plus cetuximab first line for recurrent and/or metastatic squamous cell carcinoma of the head and neck. Ann Oncol. 2010 Oct;21(10):1967-1973. doi: 10.1093/annonc/mdq077. Epub 2010 Mar 24.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Hecht M, Hahn D, Wolber P, Hautmann MG, Reichert D, Weniger S, Belka C, Bergmann T, Gohler T, Welslau M, Grosse-Thie C, Guntinas-Lichius O, von der Grun J, Balermpas P, Orlowski K, Messinger D, Stenzel KG, Fietkau R. Treatment response lowers tumor symptom burden in recurrent and/or metastatic head and neck cancer. BMC Cancer. 2020 Sep 29;20(1):933. doi: 10.1186/s12885-020-07440-w.

Licitra L, Storkel S, Kerr KM, Van Cutsem E, Pirker R, Hirsch FR, Vermorken JB, von Heydebreck A, Esser R, Celik I, Ciardiello F. Predictive value of epidermal growth factor receptor expression for first-line chemotherapy plus cetuximab in patients with head and neck and colorectal cancer: analysis of data from the EXTREME and CRYSTAL studies. Eur J Cancer. 2013 Apr;49(6):1161-8. doi: 10.1016/j.ejca.2012.11.018. Epub 2012 Dec 19.

Layout table for additonal information

Responsible Party:	Merck KGaA, Darmstadt, Germany
ClinicalTrials.gov Identifier:	NCT00122460
Other Study ID Numbers:	EMR 62202-002
First Submitted:	July 19, 2005
First Posted:	July 22, 2005
Results First Submitted:	August 25, 2011
Results First Posted:	September 30, 2011
Last Update Posted:	July 23, 2014

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