Trial Outcomes & Findings for Adjuvant Cetuximab and Chemoradiotherapy Using Either Cisplatin or Docetaxel in Treating Patients With Resected Stage III or Stage IV Squamous Cell Carcinoma or Lymphoepithelioma of the Head and Neck (NCT NCT00084318)

Last Updated: 2018-12-12

Results Overview

Two-year rates are shown (Kaplan-Meier estimates). Disease-free survival is defined as the time from randomization to local, regional, or distant progression, second primary, or death (event) or last follow-up (censored). Response criteria as follows: No evidence of disease (NED): All patients must have no measurable tumor following surgery; Local-Regional Relapse: Recurrent cancer in the tumor bed and/or neck not clearly attributable to a second primary neoplasm; biopsy confirmation is necessary; Distant Relapse: Clear evidence of distant metastases (lung, bone, brain, etc.); Biopsy is recommended where possible. A solitary lung mass/nodule is considered a second primary neoplasm unless proven otherwise.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

238 participants

Primary outcome timeframe

From randomization to 2 years

Results posted on

2018-12-12

Participant Flow

Participant milestones

Participant milestones
Measure	RT + Cisplatin + Cetuximab Loading dose of cetuximab followed by radiation therapy with weekly cisplatin and cetuximab.	RT + Docetaxel + Cetuximab Loading dose of cetuximab followed by radiation therapy (RT) with weekly docetaxel and cetuximab.
Overall Study STARTED	119	119
Overall Study COMPLETED	97	106
Overall Study NOT COMPLETED	22	13

Reasons for withdrawal

Reasons for withdrawal
Measure	RT + Cisplatin + Cetuximab Loading dose of cetuximab followed by radiation therapy with weekly cisplatin and cetuximab.	RT + Docetaxel + Cetuximab Loading dose of cetuximab followed by radiation therapy (RT) with weekly docetaxel and cetuximab.
Overall Study Withdrawal by Subject	5	2
Overall Study Protocol Violation	15	11
Overall Study No protocol treatment	2	0

Baseline Characteristics

Adjuvant Cetuximab and Chemoradiotherapy Using Either Cisplatin or Docetaxel in Treating Patients With Resected Stage III or Stage IV Squamous Cell Carcinoma or Lymphoepithelioma of the Head and Neck

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	RT + Cisplatin + Cetuximab n=97 Participants Loading dose of cetuximab followed by radiation therapy with weekly cisplatin and cetuximab.	RT + Docetaxel + Cetuximab n=106 Participants Loading dose of cetuximab followed by radiation therapy (RT) with weekly docetaxel and cetuximab.	Total n=203 Participants Total of all reporting groups
Age, Continuous	57 years n=5 Participants	55 years n=7 Participants	56 years n=5 Participants
Sex: Female, Male Female	20 Participants n=5 Participants	32 Participants n=7 Participants	52 Participants n=5 Participants
Sex: Female, Male Male	77 Participants n=5 Participants	74 Participants n=7 Participants	151 Participants n=5 Participants

PRIMARY outcome

Timeframe: From randomization to 2 years

Population: Eligible patients who started protocol treatment and did not withdraw consent.

Outcome measures

Outcome measures
Measure	RT + Cisplatin + Cetuximab n=97 Participants Loading dose of cetuximab followed by radiation therapy with weekly cisplatin and cetuximab.	RT + Docetaxel + Cetuximab n=106 Participants Loading dose of cetuximab followed by radiation therapy (RT) with weekly docetaxel and cetuximab.
Disease-free Survival	57.3 percentage of participants Interval 47.4 to 67.2	65.9 percentage of participants Interval 56.9 to 75.0

SECONDARY outcome

Timeframe: From randomization to 2 years

Population: Eligible patients who started protocol treatment and did not withdraw consent

Two-year rates are shown (Kaplan-Meier estimates). Overall survival is defined as the time from randomization to death (event) or last follow-up (censored).

Outcome measures

Outcome measures
Measure	RT + Cisplatin + Cetuximab n=97 Participants Loading dose of cetuximab followed by radiation therapy with weekly cisplatin and cetuximab.	RT + Docetaxel + Cetuximab n=106 Participants Loading dose of cetuximab followed by radiation therapy (RT) with weekly docetaxel and cetuximab.
Overall Survival	68.8 percentage of participants Interval 59.5 to 78.0	79.2 percentage of participants Interval 71.4 to 86.9

SECONDARY outcome

Timeframe: From start of treatment to end of treatment (protocol treatment lasts seven weeks).

Population: Eligible patients who started protocol treatment and did not withdraw consent

Tolerability was defined as having received 90% of the radiation dose, 95% of the cetuximab loading dose, and at least 4 weeks of cetuximab and cisplatin or docetaxel at doses 95% of the protocol prescription. The percentage of patients determined to be tolerant of treatment are shown.

Outcome measures

Outcome measures
Measure	RT + Cisplatin + Cetuximab n=97 Participants Loading dose of cetuximab followed by radiation therapy with weekly cisplatin and cetuximab.	RT + Docetaxel + Cetuximab n=106 Participants Loading dose of cetuximab followed by radiation therapy (RT) with weekly docetaxel and cetuximab.
Treatment Tolerance	80.4 percentage of participants Interval 72.5 to 88.3	84.9 percentage of participants Interval 78.1 to 91.7

SECONDARY outcome

Timeframe: From start of treatment to last follow-up. Analysis occurs at the time of the primary analysis.

Population: Eligible patients who started protocol treatment and did not withdraw consent

Each regimen was monitored for excessive acute toxicity (defined as nonhematologic grade 4 toxicity within 90 days of the start of radiation or any grade 5 toxicity). The target rate was based on the observed rate from RTOG-9501/NCT00002670 of 15%. The unacceptable rate was \>30%. \[RTOG = Radiation Therapy Oncology Group\]

Outcome measures

Outcome measures
Measure	RT + Cisplatin + Cetuximab n=97 Participants Loading dose of cetuximab followed by radiation therapy with weekly cisplatin and cetuximab.	RT + Docetaxel + Cetuximab n=106 Participants Loading dose of cetuximab followed by radiation therapy (RT) with weekly docetaxel and cetuximab.
Frequency of Toxicity (Grade 5 and Acute Non-hematologic Grade 4)	9.3 percentage of participants Interval 3.5 to 15.1	12.3 percentage of participants Interval 6.0 to 18.5

SECONDARY outcome

Timeframe: From start of treatment to last follow-up. Analysis occurs at the time of the primary endpoint analysis.

Population: Eligible patients who started protocol treatment and did not withdraw consent

Maximum grade toxicity that is definitely, probably, or possibly related to protocol treatment.

Outcome measures

Outcome measures
Measure	RT + Cisplatin + Cetuximab n=97 Participants Loading dose of cetuximab followed by radiation therapy with weekly cisplatin and cetuximab.	RT + Docetaxel + Cetuximab n=106 Participants Loading dose of cetuximab followed by radiation therapy (RT) with weekly docetaxel and cetuximab.
Frequency of Other Acute and Late Toxicity Grade 1	1.0 percentage of participants	0.0 percentage of participants
Frequency of Other Acute and Late Toxicity Grade 2	10.3 percentage of participants	9.4 percentage of participants
Frequency of Other Acute and Late Toxicity Grade 3	74.2 percentage of participants	73.6 percentage of participants
Frequency of Other Acute and Late Toxicity Grade 4	14.4 percentage of participants	16.0 percentage of participants
Frequency of Other Acute and Late Toxicity Grade 5	0.0 percentage of participants	0.9 percentage of participants

SECONDARY outcome

Timeframe: From randomization to 2 years

Population: Eligible patients who started protocol treatment and did not withdraw consent.

Two-year rate is shown (cumulative incidence estimate). Local-regional failure is defined as the time from randomization to local-regional recurrence (event), death (competing risk), or last follow-up (censored).

Outcome measures

Outcome measures
Measure	RT + Cisplatin + Cetuximab n=97 Participants Loading dose of cetuximab followed by radiation therapy with weekly cisplatin and cetuximab.	RT + Docetaxel + Cetuximab n=106 Participants Loading dose of cetuximab followed by radiation therapy (RT) with weekly docetaxel and cetuximab.
Local-regional Control	19.8 percentage of participants Interval 11.8 to 27.8	18.9 percentage of participants Interval 13.4 to 24.3

SECONDARY outcome

Timeframe: From randomization to two years

Population: Effective and reliable assessment of nuclear expression of these receptors was not achieved and therefore no data was available for analysis.

Outcome measures

Outcome data not reported

Adverse Events

RT+Cisplatin+Cetuximab

Serious events: 42 serious events

Other events: 97 other events

Deaths: 0 deaths

RT+Docetaxel+Cetuximab

Serious events: 56 serious events

Other events: 105 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Wendy Seiferheld, M.S.

NRG Oncology

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee PI's are required to abide by the sponsor's publication guidelines which require review by coauthors and subsequent review and approval by the sponsor.
Publication restrictions are in place

Restriction type: OTHER

Serious adverse events
Measure	RT+Cisplatin+Cetuximab n=97 participants at risk Loading dose of cetuximab followed by radiation therapy with weekly cisplatin and cetuximab.	RT+Docetaxel+Cetuximab n=106 participants at risk Loading dose of cetuximab followed by radiation therapy (RT) with weekly docetaxel and cetuximab.
Blood and lymphatic system disorders Febrile neutropenia	4.1% 4/97 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	0.00% 0/106 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Blood and lymphatic system disorders Hemoglobin	6.2% 6/97 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	1.9% 2/106 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Cardiac disorders Atrial fibrillation	0.00% 0/97 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	1.9% 2/106 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Cardiac disorders Cardiac general - Other	0.00% 0/97 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	1.9% 2/106 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Cardiac disorders Cardio-respiratory arrest	1.0% 1/97 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	0.00% 0/106 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Cardiac disorders Myocardial ischemia	0.00% 0/97 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	1.9% 2/106 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Cardiac disorders Supraventricular arrhythmia NOS	0.00% 0/97 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	0.94% 1/106 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Ear and labyrinth disorders Hearing impaired	2.1% 2/97 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	0.00% 0/106 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Ear and labyrinth disorders Tinnitus	1.0% 1/97 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	0.00% 0/106 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Endocrine disorders Hypothyroidism	2.1% 2/97 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	0.94% 1/106 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Eye disorders Conjunctivitis	0.00% 0/97 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	0.94% 1/106 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Gastrointestinal disorders Abdominal pain NOS	1.0% 1/97 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	0.94% 1/106 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Gastrointestinal disorders Acquired tracheo-esophageal fistula	0.00% 0/97 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	0.94% 1/106 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Gastrointestinal disorders Constipation	1.0% 1/97 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	1.9% 2/106 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Gastrointestinal disorders Diarrhea NOS	3.1% 3/97 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	3.8% 4/106 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Gastrointestinal disorders Dry mouth	9.3% 9/97 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	12.3% 13/106 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Gastrointestinal disorders Dyspepsia	1.0% 1/97 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	0.00% 0/106 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Gastrointestinal disorders Dysphagia	10.3% 10/97 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	10.4% 11/106 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Gastrointestinal disorders Esophageal stenosis acquired	0.00% 0/97 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	0.94% 1/106 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Gastrointestinal disorders Esophagitis NOS	1.0% 1/97 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	1.9% 2/106 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Gastrointestinal disorders Fistula, GI: Oral cavity	0.00% 0/97 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	1.9% 2/106 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Gastrointestinal disorders Gastrointestinal - Other	0.00% 0/97 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	1.9% 2/106 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Gastrointestinal disorders Mucositis/stomatitis (clinical exam): Large bowel	1.0% 1/97 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	0.00% 0/106 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Gastrointestinal disorders Nausea	7.2% 7/97 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	6.6% 7/106 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Gastrointestinal disorders Oral pain	2.1% 2/97 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	4.7% 5/106 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Gastrointestinal disorders Radiation mucositis	10.3% 10/97 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	11.3% 12/106 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Gastrointestinal disorders Salivary gland disorder NOS	1.0% 1/97 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	0.00% 0/106 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Gastrointestinal disorders Stomatitis	4.1% 4/97 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	7.5% 8/106 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Gastrointestinal disorders Vomiting NOS	5.2% 5/97 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	7.5% 8/106 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
General disorders Constitutional Symptoms - Other	0.00% 0/97 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	0.94% 1/106 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
General disorders Edema: head and neck	1.0% 1/97 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	3.8% 4/106 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
General disorders Fatigue	5.2% 5/97 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	3.8% 4/106 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
General disorders Pain - Other	1.0% 1/97 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	3.8% 4/106 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
General disorders Pyrexia	2.1% 2/97 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	9.4% 10/106 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
General disorders Rigors	0.00% 0/97 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	3.8% 4/106 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Immune system disorders Hypersensitivity NOS	2.1% 2/97 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	3.8% 4/106 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Infections and infestations Bladder infection NOS	1.0% 1/97 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	0.00% 0/106 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Infections and infestations Implant site infection	1.0% 1/97 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	0.00% 0/106 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Infections and infestations Infection - Other	1.0% 1/97 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	2.8% 3/106 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Infections and infestations Infection with Grade 3 or 4 neutrophils (ANC <1.0 x 10e9/L): Bladder (urinary)	1.0% 1/97 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	0.00% 0/106 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.

Other adverse events
Measure	RT+Cisplatin+Cetuximab n=97 participants at risk Loading dose of cetuximab followed by radiation therapy with weekly cisplatin and cetuximab.	RT+Docetaxel+Cetuximab n=106 participants at risk Loading dose of cetuximab followed by radiation therapy (RT) with weekly docetaxel and cetuximab.
Blood and lymphatic system disorders Blood/bone marrow - Other	6.2% 6/97 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	4.7% 5/106 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Blood and lymphatic system disorders Hemoglobin	58.8% 57/97 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	51.9% 55/106 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Ear and labyrinth disorders Auditory/ear - Other	6.2% 6/97 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	4.7% 5/106 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Ear and labyrinth disorders Hearing impaired	3.1% 3/97 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	9.4% 10/106 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Ear and labyrinth disorders Tinnitus	5.2% 5/97 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	5.7% 6/106 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Endocrine disorders Hypothyroidism	10.3% 10/97 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	14.2% 15/106 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Gastrointestinal disorders Abdominal pain NOS	6.2% 6/97 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	6.6% 7/106 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Gastrointestinal disorders Constipation	26.8% 26/97 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	33.0% 35/106 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Gastrointestinal disorders Diarrhea NOS	23.7% 23/97 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	21.7% 23/106 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Gastrointestinal disorders Dry mouth	81.4% 79/97 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	80.2% 85/106 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Gastrointestinal disorders Dyspepsia	7.2% 7/97 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	12.3% 13/106 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Gastrointestinal disorders Dysphagia	76.3% 74/97 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	81.1% 86/106 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Gastrointestinal disorders Esophageal stenosis acquired	7.2% 7/97 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	7.5% 8/106 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Gastrointestinal disorders Esophagitis NOS	9.3% 9/97 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	16.0% 17/106 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Gastrointestinal disorders Gastrointestinal - Other	10.3% 10/97 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	11.3% 12/106 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Gastrointestinal disorders Nausea	54.6% 53/97 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	46.2% 49/106 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Gastrointestinal disorders Oral pain	29.9% 29/97 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	39.6% 42/106 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Gastrointestinal disorders Radiation mucositis	56.7% 55/97 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	61.3% 65/106 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Gastrointestinal disorders Salivary gland disorder NOS	29.9% 29/97 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	34.0% 36/106 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Gastrointestinal disorders Stomatitis	21.6% 21/97 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	32.1% 34/106 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Gastrointestinal disorders Tooth disorder NOS	6.2% 6/97 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	5.7% 6/106 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Gastrointestinal disorders Vomiting NOS	34.0% 33/97 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	25.5% 27/106 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
General disorders Edema: head and neck	24.7% 24/97 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	25.5% 27/106 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
General disorders Facial pain	3.1% 3/97 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	6.6% 7/106 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
General disorders Fatigue	78.4% 76/97 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	78.3% 83/106 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
General disorders Pain - Other	12.4% 12/97 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	8.5% 9/106 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
General disorders Pyrexia	16.5% 16/97 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	15.1% 16/106 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
General disorders Rigors	7.2% 7/97 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	10.4% 11/106 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Infections and infestations Gingival infection	6.2% 6/97 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	2.8% 3/106 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Infections and infestations Infection - Other	10.3% 10/97 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	7.5% 8/106 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Injury, poisoning and procedural complications Dermatitis radiation NOS	40.2% 39/97 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	44.3% 47/106 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Injury, poisoning and procedural complications Radiation recall syndrome	29.9% 29/97 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	17.9% 19/106 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Investigations Alanine aminotransferase increased	8.2% 8/97 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	15.1% 16/106 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Investigations Aspartate aminotransferase increased	17.5% 17/97 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	22.6% 24/106 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Investigations Blood alkaline phosphatase increased	7.2% 7/97 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	15.1% 16/106 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Investigations Blood bilirubin increased	7.2% 7/97 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	7.5% 8/106 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Investigations Blood creatinine increased	5.2% 5/97 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	4.7% 5/106 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Investigations Leukopenia NOS	52.6% 51/97 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	27.4% 29/106 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Investigations Lymphopenia	20.6% 20/97 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	22.6% 24/106 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Investigations Metabolic/laboratory - Other	7.2% 7/97 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	10.4% 11/106 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.