Trial Outcomes & Findings for Abraxane in Combination With Carboplatin, Erbitux and IMRT for Locally Advanced Squamous Cancer of the Head and Neck (NCT NCT00570674)

Last Updated: 2017-11-13

Results Overview

Disease-free survival (DFS) is defined as the time from registration to the earlier of disease recurrence or death from any cause. Patients alive without a recurrence are censored at the date of last disease evaluation. 2-year disease-free survival is the probability of patients remaining alive and progression-free at 2-years from study entry estimated using Kaplan-Meier methods. Per RECIST 1.0 criteria: progressive disease (PD) is at least a 20% increase in the sum of longest diameter (LD) of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. PD for the evaluation of non-target lesions is the appearance of one or more new lesions and/or equivocal progression of non-target.

Recruitment status

TERMINATED

Study phase

PHASE1/PHASE2

Target enrollment

29 participants

Primary outcome timeframe

Disease assessments occurred 8-10 weeks following treatment end then every 4-6 weeks (yr 1), every 8-10 weeks (yr 2), quarterly (yr 3) and semiannually up to 2 yrs since last pt enrolled.

Results posted on

2017-11-13

Participant Flow

29 participants were enrolled between November 2007 and August 2011.

Participant milestones

Participant milestones
Measure	Phase I Dose Level 1: ACE-RT Phase I Dose Level 1 participants received Abraxane 20mg/m2 IV then carboplatin AUC 1.5 IV weekly during the period of radiotherapy for a total of 7 weeks. One dose (400 mg/m2 IV) of Erbitux was given prior to start of radiation, then weekly at 250 mg/m2 IV. Intensity-modulated radiotherapy (IMRT) was delivered 5 days per week with the prescribed dose of 70 Gy to the gross tumor volume, given in 2 Gy daily fractions for a total of 35 fractions.	Phase I Dose Level -1: AC-RT Phase I Dose Level -1 participants received Abraxane 20mg/m2 IV then carboplatin AUC 1.5 weekly IV during the period of radiotherapy for a total of 7 weeks. Intensity-modulated radiotherapy (IMRT) was delivered 5 days per week with the prescribed dose of 70 Gy to the gross tumor volume, given in 2 Gy daily fractions for a total of 35 fractions.	Phase I Dose Level 2: AC-RT Phase I Dose Level 2 participants received Abraxane 30mg/m2 IV then carboplatin AUC 1.5 weekly IV during the period of radiotherapy for a total of 7 weeks. Intensity-modulated radiotherapy (IMRT) was delivered 5 days per week with the prescribed dose of 70 Gy to the gross tumor volume, given in 2 Gy daily fractions for a total of 35 fractions.	Phase I Dose Level 3: AC-RT Phase I Dose Level 3 participants received Abraxane 40mg/m2 IV then carboplatin AUC 1.5 IV weekly during the period of radiotherapy for a total of 7 weeks. Intensity-modulated radiotherapy (IMRT) was delivered 5 days per week with the prescribed dose of 70 Gy to the gross tumor volume, given in 2 Gy daily fractions for a total of 35 fractions.	Phase I Dose Level 4: AC-RT Phase I Dose Level 4 participants received Abraxane 50mg/m2 IV then carboplatin AUC 1.5 IV weekly during the period of radiotherapy for a total of 7 weeks. Intensity-modulated radiotherapy (IMRT) was delivered 5 days per week with the prescribed dose of 70 Gy to the gross tumor volume, given in 2 Gy daily fractions for a total of 35 fractions.	Phase I Dose Level 4 Expansion Cohort: AC-RT Phase I Dose Level 4 participants received Abraxane 50mg/m2 IV then carboplatin AUC 1.5 IV weekly during the period of radiotherapy for a total of 7 weeks. Intensity-modulated radiotherapy (IMRT) was delivered 5 days per week with the prescribed dose of 70 Gy to the gross tumor volume, given in 2 Gy daily fractions for a total of 35 fractions. If no DLTs are observed at dose level 4 then ten additional participants (expansion cohort) will be enrolled at that dose level.
Overall Study STARTED	6	3	4	3	3	10
Overall Study Treated	6	3	3	3	3	10
Overall Study PEG Evaluable	6	3	3	3	2	10
Overall Study COMPLETED	6	3	3	3	3	10
Overall Study NOT COMPLETED	0	0	1	0	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Phase I Dose Level 1: ACE-RT Phase I Dose Level 1 participants received Abraxane 20mg/m2 IV then carboplatin AUC 1.5 IV weekly during the period of radiotherapy for a total of 7 weeks. One dose (400 mg/m2 IV) of Erbitux was given prior to start of radiation, then weekly at 250 mg/m2 IV. Intensity-modulated radiotherapy (IMRT) was delivered 5 days per week with the prescribed dose of 70 Gy to the gross tumor volume, given in 2 Gy daily fractions for a total of 35 fractions.	Phase I Dose Level -1: AC-RT Phase I Dose Level -1 participants received Abraxane 20mg/m2 IV then carboplatin AUC 1.5 weekly IV during the period of radiotherapy for a total of 7 weeks. Intensity-modulated radiotherapy (IMRT) was delivered 5 days per week with the prescribed dose of 70 Gy to the gross tumor volume, given in 2 Gy daily fractions for a total of 35 fractions.	Phase I Dose Level 2: AC-RT Phase I Dose Level 2 participants received Abraxane 30mg/m2 IV then carboplatin AUC 1.5 weekly IV during the period of radiotherapy for a total of 7 weeks. Intensity-modulated radiotherapy (IMRT) was delivered 5 days per week with the prescribed dose of 70 Gy to the gross tumor volume, given in 2 Gy daily fractions for a total of 35 fractions.	Phase I Dose Level 3: AC-RT Phase I Dose Level 3 participants received Abraxane 40mg/m2 IV then carboplatin AUC 1.5 IV weekly during the period of radiotherapy for a total of 7 weeks. Intensity-modulated radiotherapy (IMRT) was delivered 5 days per week with the prescribed dose of 70 Gy to the gross tumor volume, given in 2 Gy daily fractions for a total of 35 fractions.	Phase I Dose Level 4: AC-RT Phase I Dose Level 4 participants received Abraxane 50mg/m2 IV then carboplatin AUC 1.5 IV weekly during the period of radiotherapy for a total of 7 weeks. Intensity-modulated radiotherapy (IMRT) was delivered 5 days per week with the prescribed dose of 70 Gy to the gross tumor volume, given in 2 Gy daily fractions for a total of 35 fractions.	Phase I Dose Level 4 Expansion Cohort: AC-RT Phase I Dose Level 4 participants received Abraxane 50mg/m2 IV then carboplatin AUC 1.5 IV weekly during the period of radiotherapy for a total of 7 weeks. Intensity-modulated radiotherapy (IMRT) was delivered 5 days per week with the prescribed dose of 70 Gy to the gross tumor volume, given in 2 Gy daily fractions for a total of 35 fractions. If no DLTs are observed at dose level 4 then ten additional participants (expansion cohort) will be enrolled at that dose level.	All Phase II Participants Participants received Abraxane according to the established recommended Phase II dose of Abraxane (50mg/m2 IV) then carboplatin AUC 1.5 IV weekly during the period of radiotherapy for a total of 7 weeks. Intensity-modulated radiotherapy (IMRT) was delivered 5 days per week with the prescribed dose of 70 Gy to the gross tumor volume, given in 2 Gy daily fractions for a total of 35 fractions.
Overall Study Withdrawal by Subject	0	0	1	0	0	0	0

Baseline Characteristics

Abraxane in Combination With Carboplatin, Erbitux and IMRT for Locally Advanced Squamous Cancer of the Head and Neck

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	All Phase I Participants n=28 Participants Participants received Abraxane according to the established dose escalation schedule 50mg/m2 IV then carboplatin AUC 1.5 IV weekly during the period of radiotherapy for a total of 7 weeks. For Dose Level 1 participants, one dose (400 mg/m2 IV) of Erbitux was given prior to start of radiation, then weekly at 250 mg/m2 IV. Intensity-modulated radiotherapy (IMRT) was delivered 5 days per week with the prescribed dose of 70 Gy to the gross tumor volume, given in 2 Gy daily fractions for a total of 35 fractions.
Age, Continuous	60 years n=5 Participants
Sex: Female, Male Female	6 Participants n=5 Participants
Sex: Female, Male Male	22 Participants n=5 Participants
Region of Enrollment United States	28 Participants n=5 Participants
Primary Tumor Site Oral cavity	3 Participants n=5 Participants
Primary Tumor Site Oropharynx	17 Participants n=5 Participants
Primary Tumor Site Larynx	4 Participants n=5 Participants
Primary Tumor Site Unknown Primary	2 Participants n=5 Participants
Primary Tumor Site Other	2 Participants n=5 Participants

PRIMARY outcome

Timeframe: Adverse event assessments occurred weekly on treatment; The observation period for MTD evaluation incorporated the 7 weeks of treatment.

Population: The MTD was not reached on this trial but the recommended phase II dose was the highest dose of Abraxane evaluated.

The Abraxane MTD in combination with carboplatin and concurrent IMRT is determined by the number of participants who experience a dose limiting toxicity (DLT). See subsequent primary outcome measure for the DLT definition. The MTD is defined as the highest dose at which fewer than one-third of participants experience a DLT. If no DLTs are observed then the MTD is not reached but the highest dose may then be the recommended phase II dose.

Outcome measures

Outcome measures
Measure	All Phase I Participants n=28 Participants Participants received Abraxane according to the established dose escalation schedule then carboplatin AUC 1.5 IV weekly during the period of radiotherapy for a total of 7 weeks. For Dose Level 1 participants, one dose (400 mg/m2 IV) of Erbitux was given prior to start of radiation, then weekly at 250 mg/m2 IV. Intensity-modulated radiotherapy (IMRT) was delivered 5 days per week with the prescribed dose of 70 Gy to the gross tumor volume, given in 2 Gy daily fractions for a total of 35 fractions.	Phase I Dose Level -1: AC-RT Phase I Dose Level -1 participants received Abraxane 20mg/m2 IV then carboplatin AUC 1.5 weekly IV during the period of radiotherapy for a total of 7 weeks. Intensity-modulated radiotherapy (IMRT) was delivered 5 days per week with the prescribed dose of 70 Gy to the gross tumor volume, given in 2 Gy daily fractions for a total of 35 fractions.	Phase I Dose Level 2: AC-RT Phase I Dose Level 2 participants received Abraxane 30mg/m2 IV then carboplatin AUC 1.5 weekly IV during the period of radiotherapy for a total of 7 weeks. Intensity-modulated radiotherapy (IMRT) was delivered 5 days per week with the prescribed dose of 70 Gy to the gross tumor volume, given in 2 Gy daily fractions for a total of 35 fractions.	Phase I Dose Level 3: AC-RT Phase I Dose Level 3 participants received Abraxane 40mg/m2 IV then carboplatin AUC 1.5 IV weekly during the period of radiotherapy for a total of 7 weeks. Intensity-modulated radiotherapy (IMRT) was delivered 5 days per week with the prescribed dose of 70 Gy to the gross tumor volume, given in 2 Gy daily fractions for a total of 35 fractions.	Phase I Dose Level 4: AC-RT Phase I Dose Level 4 participants received Abraxane 50mg/m2 IV then carboplatin AUC 1.5 IV weekly during the period of radiotherapy for a total of 7 weeks. Intensity-modulated radiotherapy (IMRT) was delivered 5 days per week with the prescribed dose of 70 Gy to the gross tumor volume, given in 2 Gy daily fractions for a total of 35 fractions.
Abraxane Maximum Tolerated Dose (MTD) [Phase I]	50 mg weekly	—	—	—	—

PRIMARY outcome

Timeframe: Adverse event assessments occurred weekly on treatment; The observation period for DLT evaluation incorporated the 7 weeks of treatment.

Population: The analysis dataset is comprised of all treated patients in the dose escalation cohorts.While no DLTs were observed in the first 3 DL 1 patients, the cohort was expanded to 6 patients due to safety and tolerability concerns. Upon further review, it was resolved that the Abraxane dose should not be increased in the setting of concurrent Erbitux.

Dose limiting toxicities (DLT) were defined as treatment-related: 1) grade 3-4 non-hematological toxicity excluding untreated nausea, vomiting and diarrhea; dysphagia, esophagitis, mucositis/stomatitis, dermatitis/rash, 2) Grade 3 or greater febrile neutropenia occurring during chemoradiotherapy, 3) Grade 4 neutropenia lasting \>/= 7 days and 4) Grade 3 thrombocytopenia. Grade 4 toxicities resulting in a treatment breaks \> 7 days were considered DLTs.

Outcome measures

Outcome measures
Measure	All Phase I Participants n=6 Participants Participants received Abraxane according to the established dose escalation schedule then carboplatin AUC 1.5 IV weekly during the period of radiotherapy for a total of 7 weeks. For Dose Level 1 participants, one dose (400 mg/m2 IV) of Erbitux was given prior to start of radiation, then weekly at 250 mg/m2 IV. Intensity-modulated radiotherapy (IMRT) was delivered 5 days per week with the prescribed dose of 70 Gy to the gross tumor volume, given in 2 Gy daily fractions for a total of 35 fractions.	Phase I Dose Level -1: AC-RT n=3 Participants Phase I Dose Level -1 participants received Abraxane 20mg/m2 IV then carboplatin AUC 1.5 weekly IV during the period of radiotherapy for a total of 7 weeks. Intensity-modulated radiotherapy (IMRT) was delivered 5 days per week with the prescribed dose of 70 Gy to the gross tumor volume, given in 2 Gy daily fractions for a total of 35 fractions.	Phase I Dose Level 2: AC-RT n=3 Participants Phase I Dose Level 2 participants received Abraxane 30mg/m2 IV then carboplatin AUC 1.5 weekly IV during the period of radiotherapy for a total of 7 weeks. Intensity-modulated radiotherapy (IMRT) was delivered 5 days per week with the prescribed dose of 70 Gy to the gross tumor volume, given in 2 Gy daily fractions for a total of 35 fractions.	Phase I Dose Level 3: AC-RT n=3 Participants Phase I Dose Level 3 participants received Abraxane 40mg/m2 IV then carboplatin AUC 1.5 IV weekly during the period of radiotherapy for a total of 7 weeks. Intensity-modulated radiotherapy (IMRT) was delivered 5 days per week with the prescribed dose of 70 Gy to the gross tumor volume, given in 2 Gy daily fractions for a total of 35 fractions.	Phase I Dose Level 4: AC-RT n=3 Participants Phase I Dose Level 4 participants received Abraxane 50mg/m2 IV then carboplatin AUC 1.5 IV weekly during the period of radiotherapy for a total of 7 weeks. Intensity-modulated radiotherapy (IMRT) was delivered 5 days per week with the prescribed dose of 70 Gy to the gross tumor volume, given in 2 Gy daily fractions for a total of 35 fractions.
Dose Limiting Toxicity (DLT) [Phase I]	0 Participants with DLT	0 Participants with DLT	0 Participants with DLT	0 Participants with DLT	0 Participants with DLT

PRIMARY outcome

Timeframe: Disease assessments occurred 8-10 weeks following treatment end then every 4-6 weeks (yr 1), every 8-10 weeks (yr 2), quarterly (yr 3) and semiannually up to 2 yrs since last pt enrolled.

Population: The phase II portion planned to enroll 34 participants including the phase I expansion cohort but the study did not continue beyond phase I.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: The primary re-staging assessment for response occurred 8-10 weeks following completion of treatment. Treatment duration was a mean (range) of 7.8 weeks (6.6-10.1).

Population: The analysis dataset is comprised of all treated phase I patients. Reporting within dose cohorts is not preferred given the small sample sizes.

Overall response (OR) rate was defined as achieving partial response (PR) or complete response (CR) based on RECIST 1.0 criteria on treatment. Per RECIST 1.0 for target lesions, CR is complete disappearance of all target lesions and PR is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. To be assigned a status of CR or PR, changes in tumor measurements must be confirmed by repeat assessments performed no fewer than 4 weeks after the response criteria are first met. PR or better overall response assumes at a minimum incomplete response/stable disease (SD) for the evaluation of non-target lesions and absence of new lesions.

Outcome measures

Outcome measures
Measure	All Phase I Participants n=28 Participants Participants received Abraxane according to the established dose escalation schedule then carboplatin AUC 1.5 IV weekly during the period of radiotherapy for a total of 7 weeks. For Dose Level 1 participants, one dose (400 mg/m2 IV) of Erbitux was given prior to start of radiation, then weekly at 250 mg/m2 IV. Intensity-modulated radiotherapy (IMRT) was delivered 5 days per week with the prescribed dose of 70 Gy to the gross tumor volume, given in 2 Gy daily fractions for a total of 35 fractions.	Phase I Dose Level -1: AC-RT Phase I Dose Level -1 participants received Abraxane 20mg/m2 IV then carboplatin AUC 1.5 weekly IV during the period of radiotherapy for a total of 7 weeks. Intensity-modulated radiotherapy (IMRT) was delivered 5 days per week with the prescribed dose of 70 Gy to the gross tumor volume, given in 2 Gy daily fractions for a total of 35 fractions.	Phase I Dose Level 2: AC-RT Phase I Dose Level 2 participants received Abraxane 30mg/m2 IV then carboplatin AUC 1.5 weekly IV during the period of radiotherapy for a total of 7 weeks. Intensity-modulated radiotherapy (IMRT) was delivered 5 days per week with the prescribed dose of 70 Gy to the gross tumor volume, given in 2 Gy daily fractions for a total of 35 fractions.	Phase I Dose Level 3: AC-RT Phase I Dose Level 3 participants received Abraxane 40mg/m2 IV then carboplatin AUC 1.5 IV weekly during the period of radiotherapy for a total of 7 weeks. Intensity-modulated radiotherapy (IMRT) was delivered 5 days per week with the prescribed dose of 70 Gy to the gross tumor volume, given in 2 Gy daily fractions for a total of 35 fractions.	Phase I Dose Level 4: AC-RT Phase I Dose Level 4 participants received Abraxane 50mg/m2 IV then carboplatin AUC 1.5 IV weekly during the period of radiotherapy for a total of 7 weeks. Intensity-modulated radiotherapy (IMRT) was delivered 5 days per week with the prescribed dose of 70 Gy to the gross tumor volume, given in 2 Gy daily fractions for a total of 35 fractions.
Overall Response Rate [Phase I]	.964 proportion of participants Interval 0.816 to 0.999	—	—	—	—

SECONDARY outcome

Timeframe: All patients were followed for survival for a minimum of 2 years. Median survival follow-up was 44.7 months (range 10-70) in this study cohort.

Population: The analysis dataset is comprised of all treated phase I patients. Reporting within dose cohorts is not preferred given the small sample sizes.

2-year overall survival is the proportion of patients alive at 2-years from study entry.

Outcome measures

Outcome measures
Measure	All Phase I Participants n=28 Participants Participants received Abraxane according to the established dose escalation schedule then carboplatin AUC 1.5 IV weekly during the period of radiotherapy for a total of 7 weeks. For Dose Level 1 participants, one dose (400 mg/m2 IV) of Erbitux was given prior to start of radiation, then weekly at 250 mg/m2 IV. Intensity-modulated radiotherapy (IMRT) was delivered 5 days per week with the prescribed dose of 70 Gy to the gross tumor volume, given in 2 Gy daily fractions for a total of 35 fractions.	Phase I Dose Level -1: AC-RT Phase I Dose Level -1 participants received Abraxane 20mg/m2 IV then carboplatin AUC 1.5 weekly IV during the period of radiotherapy for a total of 7 weeks. Intensity-modulated radiotherapy (IMRT) was delivered 5 days per week with the prescribed dose of 70 Gy to the gross tumor volume, given in 2 Gy daily fractions for a total of 35 fractions.	Phase I Dose Level 2: AC-RT Phase I Dose Level 2 participants received Abraxane 30mg/m2 IV then carboplatin AUC 1.5 weekly IV during the period of radiotherapy for a total of 7 weeks. Intensity-modulated radiotherapy (IMRT) was delivered 5 days per week with the prescribed dose of 70 Gy to the gross tumor volume, given in 2 Gy daily fractions for a total of 35 fractions.	Phase I Dose Level 3: AC-RT Phase I Dose Level 3 participants received Abraxane 40mg/m2 IV then carboplatin AUC 1.5 IV weekly during the period of radiotherapy for a total of 7 weeks. Intensity-modulated radiotherapy (IMRT) was delivered 5 days per week with the prescribed dose of 70 Gy to the gross tumor volume, given in 2 Gy daily fractions for a total of 35 fractions.	Phase I Dose Level 4: AC-RT Phase I Dose Level 4 participants received Abraxane 50mg/m2 IV then carboplatin AUC 1.5 IV weekly during the period of radiotherapy for a total of 7 weeks. Intensity-modulated radiotherapy (IMRT) was delivered 5 days per week with the prescribed dose of 70 Gy to the gross tumor volume, given in 2 Gy daily fractions for a total of 35 fractions.
2-Year Overall Survival [Phase I]	.929 proportion of participants Interval 0.765 to 0.991	—	—	—	—

SECONDARY outcome

Timeframe: Assessed until time of PEG removal which was up to 18.4 months in this study cohort.

Population: The analysis dataset is comprised of all patients with date of PEG removal (evaluable). Reporting within dose cohorts is not preferred given the small sample sizes.

Estimated as the time from registration to the date of PEG removal.

Outcome measures

Outcome measures
Measure	All Phase I Participants n=27 Participants Participants received Abraxane according to the established dose escalation schedule then carboplatin AUC 1.5 IV weekly during the period of radiotherapy for a total of 7 weeks. For Dose Level 1 participants, one dose (400 mg/m2 IV) of Erbitux was given prior to start of radiation, then weekly at 250 mg/m2 IV. Intensity-modulated radiotherapy (IMRT) was delivered 5 days per week with the prescribed dose of 70 Gy to the gross tumor volume, given in 2 Gy daily fractions for a total of 35 fractions.	Phase I Dose Level -1: AC-RT Phase I Dose Level -1 participants received Abraxane 20mg/m2 IV then carboplatin AUC 1.5 weekly IV during the period of radiotherapy for a total of 7 weeks. Intensity-modulated radiotherapy (IMRT) was delivered 5 days per week with the prescribed dose of 70 Gy to the gross tumor volume, given in 2 Gy daily fractions for a total of 35 fractions.	Phase I Dose Level 2: AC-RT Phase I Dose Level 2 participants received Abraxane 30mg/m2 IV then carboplatin AUC 1.5 weekly IV during the period of radiotherapy for a total of 7 weeks. Intensity-modulated radiotherapy (IMRT) was delivered 5 days per week with the prescribed dose of 70 Gy to the gross tumor volume, given in 2 Gy daily fractions for a total of 35 fractions.	Phase I Dose Level 3: AC-RT Phase I Dose Level 3 participants received Abraxane 40mg/m2 IV then carboplatin AUC 1.5 IV weekly during the period of radiotherapy for a total of 7 weeks. Intensity-modulated radiotherapy (IMRT) was delivered 5 days per week with the prescribed dose of 70 Gy to the gross tumor volume, given in 2 Gy daily fractions for a total of 35 fractions.	Phase I Dose Level 4: AC-RT Phase I Dose Level 4 participants received Abraxane 50mg/m2 IV then carboplatin AUC 1.5 IV weekly during the period of radiotherapy for a total of 7 weeks. Intensity-modulated radiotherapy (IMRT) was delivered 5 days per week with the prescribed dose of 70 Gy to the gross tumor volume, given in 2 Gy daily fractions for a total of 35 fractions.
Duration PEG Therapy	5.4 months Interval 2.4 to 18.4	—	—	—	—

SECONDARY outcome

Timeframe: baseline and 4 months

Population: The analysis dataset is comprised of patients with evaluable data at the 2 assessment timepoints: baseline and 4 months.

The FACT-H\&N is a multidimensional, self-report QoL instrument specifically designed for use with head and neck cancer patients. It is comprised of 27 core items from the FACT-G (Version 4), an established survey which assesses the impact of cancer therapy in four domains: physical, social/family, emotional, and functional. \[Cella, D, et al. JCO 1993(11)\]. It is supplemented with a validated measure of 12 site specific items to assess for head and neck related symptoms. \[D'Antonio L, Zimmerman G, et al. Cancer 1996 (77)\] Each item is rated on a 0 to 4 Likert type scale, and then combined to produce subscale scores for each domain, as well as a global QoL score (range: 0-156). Higher scores represent better QoL. The change score is calculated as post-baseline less baseline; therefore, a negative value indicates a decrease in score and correspondingly a decrease in QoL.

Outcome measures

Outcome measures
Measure	All Phase I Participants n=15 Participants Participants received Abraxane according to the established dose escalation schedule then carboplatin AUC 1.5 IV weekly during the period of radiotherapy for a total of 7 weeks. For Dose Level 1 participants, one dose (400 mg/m2 IV) of Erbitux was given prior to start of radiation, then weekly at 250 mg/m2 IV. Intensity-modulated radiotherapy (IMRT) was delivered 5 days per week with the prescribed dose of 70 Gy to the gross tumor volume, given in 2 Gy daily fractions for a total of 35 fractions.	Phase I Dose Level -1: AC-RT Phase I Dose Level -1 participants received Abraxane 20mg/m2 IV then carboplatin AUC 1.5 weekly IV during the period of radiotherapy for a total of 7 weeks. Intensity-modulated radiotherapy (IMRT) was delivered 5 days per week with the prescribed dose of 70 Gy to the gross tumor volume, given in 2 Gy daily fractions for a total of 35 fractions.	Phase I Dose Level 2: AC-RT Phase I Dose Level 2 participants received Abraxane 30mg/m2 IV then carboplatin AUC 1.5 weekly IV during the period of radiotherapy for a total of 7 weeks. Intensity-modulated radiotherapy (IMRT) was delivered 5 days per week with the prescribed dose of 70 Gy to the gross tumor volume, given in 2 Gy daily fractions for a total of 35 fractions.	Phase I Dose Level 3: AC-RT Phase I Dose Level 3 participants received Abraxane 40mg/m2 IV then carboplatin AUC 1.5 IV weekly during the period of radiotherapy for a total of 7 weeks. Intensity-modulated radiotherapy (IMRT) was delivered 5 days per week with the prescribed dose of 70 Gy to the gross tumor volume, given in 2 Gy daily fractions for a total of 35 fractions.	Phase I Dose Level 4: AC-RT Phase I Dose Level 4 participants received Abraxane 50mg/m2 IV then carboplatin AUC 1.5 IV weekly during the period of radiotherapy for a total of 7 weeks. Intensity-modulated radiotherapy (IMRT) was delivered 5 days per week with the prescribed dose of 70 Gy to the gross tumor volume, given in 2 Gy daily fractions for a total of 35 fractions.
Change in FACT-H&N Score From Baseline to 4 Months	-21 units on a scale Interval -34.0 to 16.2	—	—	—	—

SECONDARY outcome

Timeframe: Baseline and 6 months

Population: The analysis dataset is comprised of patients with evaluable data at the 2 assessment timepoints: baseline and 6 months.

he FACT-H\&N is a multidimensional, self-report QoL instrument specifically designed for use with head and neck cancer patients. It is comprised of 27 core items from the FACT-G (Version 4), an established survey which assesses the impact of cancer therapy in four domains: physical, social/family, emotional, and functional. \[Cella, D, et al. JCO 1993(11)\]. It is supplemented with a validated measure of 12 site specific items to assess for head and neck related symptoms. \[D'Antonio L, Zimmerman G, et al. Cancer 1996 (77)\] Each item is rated on a 0 to 4 Likert type scale, and then combined to produce subscale scores for each domain, as well as a global QoL score (range: 0-156). Higher scores represent better QoL. The change score is calculated as post-baseline less baseline; therefore, a negative value indicates a decrease in score and correspondingly a decrease in QoL.

Outcome measures

Outcome measures
Measure	All Phase I Participants n=19 Participants Participants received Abraxane according to the established dose escalation schedule then carboplatin AUC 1.5 IV weekly during the period of radiotherapy for a total of 7 weeks. For Dose Level 1 participants, one dose (400 mg/m2 IV) of Erbitux was given prior to start of radiation, then weekly at 250 mg/m2 IV. Intensity-modulated radiotherapy (IMRT) was delivered 5 days per week with the prescribed dose of 70 Gy to the gross tumor volume, given in 2 Gy daily fractions for a total of 35 fractions.	Phase I Dose Level -1: AC-RT Phase I Dose Level -1 participants received Abraxane 20mg/m2 IV then carboplatin AUC 1.5 weekly IV during the period of radiotherapy for a total of 7 weeks. Intensity-modulated radiotherapy (IMRT) was delivered 5 days per week with the prescribed dose of 70 Gy to the gross tumor volume, given in 2 Gy daily fractions for a total of 35 fractions.	Phase I Dose Level 2: AC-RT Phase I Dose Level 2 participants received Abraxane 30mg/m2 IV then carboplatin AUC 1.5 weekly IV during the period of radiotherapy for a total of 7 weeks. Intensity-modulated radiotherapy (IMRT) was delivered 5 days per week with the prescribed dose of 70 Gy to the gross tumor volume, given in 2 Gy daily fractions for a total of 35 fractions.	Phase I Dose Level 3: AC-RT Phase I Dose Level 3 participants received Abraxane 40mg/m2 IV then carboplatin AUC 1.5 IV weekly during the period of radiotherapy for a total of 7 weeks. Intensity-modulated radiotherapy (IMRT) was delivered 5 days per week with the prescribed dose of 70 Gy to the gross tumor volume, given in 2 Gy daily fractions for a total of 35 fractions.	Phase I Dose Level 4: AC-RT Phase I Dose Level 4 participants received Abraxane 50mg/m2 IV then carboplatin AUC 1.5 IV weekly during the period of radiotherapy for a total of 7 weeks. Intensity-modulated radiotherapy (IMRT) was delivered 5 days per week with the prescribed dose of 70 Gy to the gross tumor volume, given in 2 Gy daily fractions for a total of 35 fractions.
Change in FACT-H&N Score From Baseline to 6 Months	-9 units on a scale Interval -28.4 to 13.3	—	—	—	—

SECONDARY outcome

Timeframe: Baseline and 12 months

Population: The analysis dataset is comprised of patients with evaluable data at the 2 assessment timepoints: baseline and 12 months.

Outcome measures

Outcome measures
Measure	All Phase I Participants n=17 Participants Participants received Abraxane according to the established dose escalation schedule then carboplatin AUC 1.5 IV weekly during the period of radiotherapy for a total of 7 weeks. For Dose Level 1 participants, one dose (400 mg/m2 IV) of Erbitux was given prior to start of radiation, then weekly at 250 mg/m2 IV. Intensity-modulated radiotherapy (IMRT) was delivered 5 days per week with the prescribed dose of 70 Gy to the gross tumor volume, given in 2 Gy daily fractions for a total of 35 fractions.	Phase I Dose Level -1: AC-RT Phase I Dose Level -1 participants received Abraxane 20mg/m2 IV then carboplatin AUC 1.5 weekly IV during the period of radiotherapy for a total of 7 weeks. Intensity-modulated radiotherapy (IMRT) was delivered 5 days per week with the prescribed dose of 70 Gy to the gross tumor volume, given in 2 Gy daily fractions for a total of 35 fractions.	Phase I Dose Level 2: AC-RT Phase I Dose Level 2 participants received Abraxane 30mg/m2 IV then carboplatin AUC 1.5 weekly IV during the period of radiotherapy for a total of 7 weeks. Intensity-modulated radiotherapy (IMRT) was delivered 5 days per week with the prescribed dose of 70 Gy to the gross tumor volume, given in 2 Gy daily fractions for a total of 35 fractions.	Phase I Dose Level 3: AC-RT Phase I Dose Level 3 participants received Abraxane 40mg/m2 IV then carboplatin AUC 1.5 IV weekly during the period of radiotherapy for a total of 7 weeks. Intensity-modulated radiotherapy (IMRT) was delivered 5 days per week with the prescribed dose of 70 Gy to the gross tumor volume, given in 2 Gy daily fractions for a total of 35 fractions.	Phase I Dose Level 4: AC-RT Phase I Dose Level 4 participants received Abraxane 50mg/m2 IV then carboplatin AUC 1.5 IV weekly during the period of radiotherapy for a total of 7 weeks. Intensity-modulated radiotherapy (IMRT) was delivered 5 days per week with the prescribed dose of 70 Gy to the gross tumor volume, given in 2 Gy daily fractions for a total of 35 fractions.
Change in FACT-H&N Score From Baseline to 12 Months	-4.2 units on a scale Interval -33.0 to 18.0	—	—	—	—

SECONDARY outcome

Timeframe: Baseline and 24 months

Population: The analysis dataset is comprised of patients with evaluable data at the 2 assessment timepoints: baseline and 24 months.

Outcome measures

Outcome measures
Measure	All Phase I Participants n=12 Participants Participants received Abraxane according to the established dose escalation schedule then carboplatin AUC 1.5 IV weekly during the period of radiotherapy for a total of 7 weeks. For Dose Level 1 participants, one dose (400 mg/m2 IV) of Erbitux was given prior to start of radiation, then weekly at 250 mg/m2 IV. Intensity-modulated radiotherapy (IMRT) was delivered 5 days per week with the prescribed dose of 70 Gy to the gross tumor volume, given in 2 Gy daily fractions for a total of 35 fractions.	Phase I Dose Level -1: AC-RT Phase I Dose Level -1 participants received Abraxane 20mg/m2 IV then carboplatin AUC 1.5 weekly IV during the period of radiotherapy for a total of 7 weeks. Intensity-modulated radiotherapy (IMRT) was delivered 5 days per week with the prescribed dose of 70 Gy to the gross tumor volume, given in 2 Gy daily fractions for a total of 35 fractions.	Phase I Dose Level 2: AC-RT Phase I Dose Level 2 participants received Abraxane 30mg/m2 IV then carboplatin AUC 1.5 weekly IV during the period of radiotherapy for a total of 7 weeks. Intensity-modulated radiotherapy (IMRT) was delivered 5 days per week with the prescribed dose of 70 Gy to the gross tumor volume, given in 2 Gy daily fractions for a total of 35 fractions.	Phase I Dose Level 3: AC-RT Phase I Dose Level 3 participants received Abraxane 40mg/m2 IV then carboplatin AUC 1.5 IV weekly during the period of radiotherapy for a total of 7 weeks. Intensity-modulated radiotherapy (IMRT) was delivered 5 days per week with the prescribed dose of 70 Gy to the gross tumor volume, given in 2 Gy daily fractions for a total of 35 fractions.	Phase I Dose Level 4: AC-RT Phase I Dose Level 4 participants received Abraxane 50mg/m2 IV then carboplatin AUC 1.5 IV weekly during the period of radiotherapy for a total of 7 weeks. Intensity-modulated radiotherapy (IMRT) was delivered 5 days per week with the prescribed dose of 70 Gy to the gross tumor volume, given in 2 Gy daily fractions for a total of 35 fractions.
Change in FACT-H&N Score From Baseline to 24 Months	4.3 units on a scale Interval -25.0 to 24.0	—	—	—	—

Adverse Events

All Phase I Participants

Serious events: 26 serious events

Other events: 28 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	All Phase I Participants n=28 participants at risk Participants received Abraxane according to the established dose escalation schedule then carboplatin AUC 1.5 IV weekly during the period of radiotherapy for a total of 7 weeks. For Dose Level 1 participants, one dose (400 mg/m2 IV) of Erbitux was given prior to start of radiation, then weekly at 250 mg/m2 IV. Intensity-modulated radiotherapy (IMRT) was delivered 5 days per week with the prescribed dose of 70 Gy to the gross tumor volume, given in 2 Gy daily fractions for a total of 35 fractions.
Blood and lymphatic system disorders Febrile neutropenia	3.6% 1/28 • Participants were assessed weekly on treatment and at weeks 4 and 8 post treatment. Treatment duration was a mean (range) of 7.8 weeks (6.6-10.1). Maximum grade toxicity by type was first calculated including adverse events with treatment-attribution of possibly, probably or definitely related to either chemotherapy or radiation therapy. Serious and Other AEs were defined as grades 3-5 and grades 1-2, respectively, per CTCAEv3.
Gastrointestinal disorders Distention/bloating, abdominal	3.6% 1/28 • Participants were assessed weekly on treatment and at weeks 4 and 8 post treatment. Treatment duration was a mean (range) of 7.8 weeks (6.6-10.1). Maximum grade toxicity by type was first calculated including adverse events with treatment-attribution of possibly, probably or definitely related to either chemotherapy or radiation therapy. Serious and Other AEs were defined as grades 3-5 and grades 1-2, respectively, per CTCAEv3.
Gastrointestinal disorders Dry mouth	3.6% 1/28 • Participants were assessed weekly on treatment and at weeks 4 and 8 post treatment. Treatment duration was a mean (range) of 7.8 weeks (6.6-10.1). Maximum grade toxicity by type was first calculated including adverse events with treatment-attribution of possibly, probably or definitely related to either chemotherapy or radiation therapy. Serious and Other AEs were defined as grades 3-5 and grades 1-2, respectively, per CTCAEv3.
Gastrointestinal disorders Dysphagia	60.7% 17/28 • Participants were assessed weekly on treatment and at weeks 4 and 8 post treatment. Treatment duration was a mean (range) of 7.8 weeks (6.6-10.1). Maximum grade toxicity by type was first calculated including adverse events with treatment-attribution of possibly, probably or definitely related to either chemotherapy or radiation therapy. Serious and Other AEs were defined as grades 3-5 and grades 1-2, respectively, per CTCAEv3.
Gastrointestinal disorders Muco/stomatitis by exam, oral cavity	64.3% 18/28 • Participants were assessed weekly on treatment and at weeks 4 and 8 post treatment. Treatment duration was a mean (range) of 7.8 weeks (6.6-10.1). Maximum grade toxicity by type was first calculated including adverse events with treatment-attribution of possibly, probably or definitely related to either chemotherapy or radiation therapy. Serious and Other AEs were defined as grades 3-5 and grades 1-2, respectively, per CTCAEv3.
Gastrointestinal disorders Nausea	7.1% 2/28 • Participants were assessed weekly on treatment and at weeks 4 and 8 post treatment. Treatment duration was a mean (range) of 7.8 weeks (6.6-10.1). Maximum grade toxicity by type was first calculated including adverse events with treatment-attribution of possibly, probably or definitely related to either chemotherapy or radiation therapy. Serious and Other AEs were defined as grades 3-5 and grades 1-2, respectively, per CTCAEv3.
Gastrointestinal disorders Salivary	3.6% 1/28 • Participants were assessed weekly on treatment and at weeks 4 and 8 post treatment. Treatment duration was a mean (range) of 7.8 weeks (6.6-10.1). Maximum grade toxicity by type was first calculated including adverse events with treatment-attribution of possibly, probably or definitely related to either chemotherapy or radiation therapy. Serious and Other AEs were defined as grades 3-5 and grades 1-2, respectively, per CTCAEv3.
Gastrointestinal disorders Vomiting	3.6% 1/28 • Participants were assessed weekly on treatment and at weeks 4 and 8 post treatment. Treatment duration was a mean (range) of 7.8 weeks (6.6-10.1). Maximum grade toxicity by type was first calculated including adverse events with treatment-attribution of possibly, probably or definitely related to either chemotherapy or radiation therapy. Serious and Other AEs were defined as grades 3-5 and grades 1-2, respectively, per CTCAEv3.
Gastrointestinal disorders Abdomen, pain	3.6% 1/28 • Participants were assessed weekly on treatment and at weeks 4 and 8 post treatment. Treatment duration was a mean (range) of 7.8 weeks (6.6-10.1). Maximum grade toxicity by type was first calculated including adverse events with treatment-attribution of possibly, probably or definitely related to either chemotherapy or radiation therapy. Serious and Other AEs were defined as grades 3-5 and grades 1-2, respectively, per CTCAEv3.
Gastrointestinal disorders Oral cavity, pain	10.7% 3/28 • Participants were assessed weekly on treatment and at weeks 4 and 8 post treatment. Treatment duration was a mean (range) of 7.8 weeks (6.6-10.1). Maximum grade toxicity by type was first calculated including adverse events with treatment-attribution of possibly, probably or definitely related to either chemotherapy or radiation therapy. Serious and Other AEs were defined as grades 3-5 and grades 1-2, respectively, per CTCAEv3.
General disorders Fatigue	3.6% 1/28 • Participants were assessed weekly on treatment and at weeks 4 and 8 post treatment. Treatment duration was a mean (range) of 7.8 weeks (6.6-10.1). Maximum grade toxicity by type was first calculated including adverse events with treatment-attribution of possibly, probably or definitely related to either chemotherapy or radiation therapy. Serious and Other AEs were defined as grades 3-5 and grades 1-2, respectively, per CTCAEv3.
General disorders Edema head and neck	3.6% 1/28 • Participants were assessed weekly on treatment and at weeks 4 and 8 post treatment. Treatment duration was a mean (range) of 7.8 weeks (6.6-10.1). Maximum grade toxicity by type was first calculated including adverse events with treatment-attribution of possibly, probably or definitely related to either chemotherapy or radiation therapy. Serious and Other AEs were defined as grades 3-5 and grades 1-2, respectively, per CTCAEv3.
Injury, poisoning and procedural complications Chemoradiation dermatitis	28.6% 8/28 • Participants were assessed weekly on treatment and at weeks 4 and 8 post treatment. Treatment duration was a mean (range) of 7.8 weeks (6.6-10.1). Maximum grade toxicity by type was first calculated including adverse events with treatment-attribution of possibly, probably or definitely related to either chemotherapy or radiation therapy. Serious and Other AEs were defined as grades 3-5 and grades 1-2, respectively, per CTCAEv3.
Investigations Leukocytes	3.6% 1/28 • Participants were assessed weekly on treatment and at weeks 4 and 8 post treatment. Treatment duration was a mean (range) of 7.8 weeks (6.6-10.1). Maximum grade toxicity by type was first calculated including adverse events with treatment-attribution of possibly, probably or definitely related to either chemotherapy or radiation therapy. Serious and Other AEs were defined as grades 3-5 and grades 1-2, respectively, per CTCAEv3.
Investigations Weight loss	3.6% 1/28 • Participants were assessed weekly on treatment and at weeks 4 and 8 post treatment. Treatment duration was a mean (range) of 7.8 weeks (6.6-10.1). Maximum grade toxicity by type was first calculated including adverse events with treatment-attribution of possibly, probably or definitely related to either chemotherapy or radiation therapy. Serious and Other AEs were defined as grades 3-5 and grades 1-2, respectively, per CTCAEv3.
Nervous system disorders Dizziness	3.6% 1/28 • Participants were assessed weekly on treatment and at weeks 4 and 8 post treatment. Treatment duration was a mean (range) of 7.8 weeks (6.6-10.1). Maximum grade toxicity by type was first calculated including adverse events with treatment-attribution of possibly, probably or definitely related to either chemotherapy or radiation therapy. Serious and Other AEs were defined as grades 3-5 and grades 1-2, respectively, per CTCAEv3.
Nervous system disorders Syncope	3.6% 1/28 • Participants were assessed weekly on treatment and at weeks 4 and 8 post treatment. Treatment duration was a mean (range) of 7.8 weeks (6.6-10.1). Maximum grade toxicity by type was first calculated including adverse events with treatment-attribution of possibly, probably or definitely related to either chemotherapy or radiation therapy. Serious and Other AEs were defined as grades 3-5 and grades 1-2, respectively, per CTCAEv3.
Psychiatric disorders Confusion	3.6% 1/28 • Participants were assessed weekly on treatment and at weeks 4 and 8 post treatment. Treatment duration was a mean (range) of 7.8 weeks (6.6-10.1). Maximum grade toxicity by type was first calculated including adverse events with treatment-attribution of possibly, probably or definitely related to either chemotherapy or radiation therapy. Serious and Other AEs were defined as grades 3-5 and grades 1-2, respectively, per CTCAEv3.
Psychiatric disorders Anxiety	3.6% 1/28 • Participants were assessed weekly on treatment and at weeks 4 and 8 post treatment. Treatment duration was a mean (range) of 7.8 weeks (6.6-10.1). Maximum grade toxicity by type was first calculated including adverse events with treatment-attribution of possibly, probably or definitely related to either chemotherapy or radiation therapy. Serious and Other AEs were defined as grades 3-5 and grades 1-2, respectively, per CTCAEv3.
Psychiatric disorders Depression	3.6% 1/28 • Participants were assessed weekly on treatment and at weeks 4 and 8 post treatment. Treatment duration was a mean (range) of 7.8 weeks (6.6-10.1). Maximum grade toxicity by type was first calculated including adverse events with treatment-attribution of possibly, probably or definitely related to either chemotherapy or radiation therapy. Serious and Other AEs were defined as grades 3-5 and grades 1-2, respectively, per CTCAEv3.
Respiratory, thoracic and mediastinal disorders Voice changes/dysarthria	3.6% 1/28 • Participants were assessed weekly on treatment and at weeks 4 and 8 post treatment. Treatment duration was a mean (range) of 7.8 weeks (6.6-10.1). Maximum grade toxicity by type was first calculated including adverse events with treatment-attribution of possibly, probably or definitely related to either chemotherapy or radiation therapy. Serious and Other AEs were defined as grades 3-5 and grades 1-2, respectively, per CTCAEv3.
Skin and subcutaneous tissue disorders Rash: acne/acneiform	3.6% 1/28 • Participants were assessed weekly on treatment and at weeks 4 and 8 post treatment. Treatment duration was a mean (range) of 7.8 weeks (6.6-10.1). Maximum grade toxicity by type was first calculated including adverse events with treatment-attribution of possibly, probably or definitely related to either chemotherapy or radiation therapy. Serious and Other AEs were defined as grades 3-5 and grades 1-2, respectively, per CTCAEv3.
Skin and subcutaneous tissue disorders Skin-other	3.6% 1/28 • Participants were assessed weekly on treatment and at weeks 4 and 8 post treatment. Treatment duration was a mean (range) of 7.8 weeks (6.6-10.1). Maximum grade toxicity by type was first calculated including adverse events with treatment-attribution of possibly, probably or definitely related to either chemotherapy or radiation therapy. Serious and Other AEs were defined as grades 3-5 and grades 1-2, respectively, per CTCAEv3.
Vascular disorders Thrombosis/thrombus/embolism	3.6% 1/28 • Participants were assessed weekly on treatment and at weeks 4 and 8 post treatment. Treatment duration was a mean (range) of 7.8 weeks (6.6-10.1). Maximum grade toxicity by type was first calculated including adverse events with treatment-attribution of possibly, probably or definitely related to either chemotherapy or radiation therapy. Serious and Other AEs were defined as grades 3-5 and grades 1-2, respectively, per CTCAEv3.

Other adverse events

Other adverse events
Measure	All Phase I Participants n=28 participants at risk Participants received Abraxane according to the established dose escalation schedule then carboplatin AUC 1.5 IV weekly during the period of radiotherapy for a total of 7 weeks. For Dose Level 1 participants, one dose (400 mg/m2 IV) of Erbitux was given prior to start of radiation, then weekly at 250 mg/m2 IV. Intensity-modulated radiotherapy (IMRT) was delivered 5 days per week with the prescribed dose of 70 Gy to the gross tumor volume, given in 2 Gy daily fractions for a total of 35 fractions.
Blood and lymphatic system disorders Hemoglobin	17.9% 5/28 • Participants were assessed weekly on treatment and at weeks 4 and 8 post treatment. Treatment duration was a mean (range) of 7.8 weeks (6.6-10.1). Maximum grade toxicity by type was first calculated including adverse events with treatment-attribution of possibly, probably or definitely related to either chemotherapy or radiation therapy. Serious and Other AEs were defined as grades 3-5 and grades 1-2, respectively, per CTCAEv3.
Ear and labyrinth disorders External ear, pain	7.1% 2/28 • Participants were assessed weekly on treatment and at weeks 4 and 8 post treatment. Treatment duration was a mean (range) of 7.8 weeks (6.6-10.1). Maximum grade toxicity by type was first calculated including adverse events with treatment-attribution of possibly, probably or definitely related to either chemotherapy or radiation therapy. Serious and Other AEs were defined as grades 3-5 and grades 1-2, respectively, per CTCAEv3.
Ear and labyrinth disorders Hearing w/w-o audiogr in monitor prg	3.6% 1/28 • Participants were assessed weekly on treatment and at weeks 4 and 8 post treatment. Treatment duration was a mean (range) of 7.8 weeks (6.6-10.1). Maximum grade toxicity by type was first calculated including adverse events with treatment-attribution of possibly, probably or definitely related to either chemotherapy or radiation therapy. Serious and Other AEs were defined as grades 3-5 and grades 1-2, respectively, per CTCAEv3.
Ear and labyrinth disorders Middle ear, pain	14.3% 4/28 • Participants were assessed weekly on treatment and at weeks 4 and 8 post treatment. Treatment duration was a mean (range) of 7.8 weeks (6.6-10.1). Maximum grade toxicity by type was first calculated including adverse events with treatment-attribution of possibly, probably or definitely related to either chemotherapy or radiation therapy. Serious and Other AEs were defined as grades 3-5 and grades 1-2, respectively, per CTCAEv3.
Ear and labyrinth disorders Otitis, middle ear (non-infectious)	3.6% 1/28 • Participants were assessed weekly on treatment and at weeks 4 and 8 post treatment. Treatment duration was a mean (range) of 7.8 weeks (6.6-10.1). Maximum grade toxicity by type was first calculated including adverse events with treatment-attribution of possibly, probably or definitely related to either chemotherapy or radiation therapy. Serious and Other AEs were defined as grades 3-5 and grades 1-2, respectively, per CTCAEv3.
Eye disorders Keratitis	3.6% 1/28 • Participants were assessed weekly on treatment and at weeks 4 and 8 post treatment. Treatment duration was a mean (range) of 7.8 weeks (6.6-10.1). Maximum grade toxicity by type was first calculated including adverse events with treatment-attribution of possibly, probably or definitely related to either chemotherapy or radiation therapy. Serious and Other AEs were defined as grades 3-5 and grades 1-2, respectively, per CTCAEv3.
Eye disorders Tearing	3.6% 1/28 • Participants were assessed weekly on treatment and at weeks 4 and 8 post treatment. Treatment duration was a mean (range) of 7.8 weeks (6.6-10.1). Maximum grade toxicity by type was first calculated including adverse events with treatment-attribution of possibly, probably or definitely related to either chemotherapy or radiation therapy. Serious and Other AEs were defined as grades 3-5 and grades 1-2, respectively, per CTCAEv3.
Gastrointestinal disorders Abdomen, pain	21.4% 6/28 • Participants were assessed weekly on treatment and at weeks 4 and 8 post treatment. Treatment duration was a mean (range) of 7.8 weeks (6.6-10.1). Maximum grade toxicity by type was first calculated including adverse events with treatment-attribution of possibly, probably or definitely related to either chemotherapy or radiation therapy. Serious and Other AEs were defined as grades 3-5 and grades 1-2, respectively, per CTCAEv3.
Gastrointestinal disorders Constipation	82.1% 23/28 • Participants were assessed weekly on treatment and at weeks 4 and 8 post treatment. Treatment duration was a mean (range) of 7.8 weeks (6.6-10.1). Maximum grade toxicity by type was first calculated including adverse events with treatment-attribution of possibly, probably or definitely related to either chemotherapy or radiation therapy. Serious and Other AEs were defined as grades 3-5 and grades 1-2, respectively, per CTCAEv3.
Gastrointestinal disorders Diarrhea w/o prior colostomy	67.9% 19/28 • Participants were assessed weekly on treatment and at weeks 4 and 8 post treatment. Treatment duration was a mean (range) of 7.8 weeks (6.6-10.1). Maximum grade toxicity by type was first calculated including adverse events with treatment-attribution of possibly, probably or definitely related to either chemotherapy or radiation therapy. Serious and Other AEs were defined as grades 3-5 and grades 1-2, respectively, per CTCAEv3.
Gastrointestinal disorders Dry mouth	92.9% 26/28 • Participants were assessed weekly on treatment and at weeks 4 and 8 post treatment. Treatment duration was a mean (range) of 7.8 weeks (6.6-10.1). Maximum grade toxicity by type was first calculated including adverse events with treatment-attribution of possibly, probably or definitely related to either chemotherapy or radiation therapy. Serious and Other AEs were defined as grades 3-5 and grades 1-2, respectively, per CTCAEv3.
Gastrointestinal disorders Dyspepsia	28.6% 8/28 • Participants were assessed weekly on treatment and at weeks 4 and 8 post treatment. Treatment duration was a mean (range) of 7.8 weeks (6.6-10.1). Maximum grade toxicity by type was first calculated including adverse events with treatment-attribution of possibly, probably or definitely related to either chemotherapy or radiation therapy. Serious and Other AEs were defined as grades 3-5 and grades 1-2, respectively, per CTCAEv3.
Gastrointestinal disorders Dysphagia	32.1% 9/28 • Participants were assessed weekly on treatment and at weeks 4 and 8 post treatment. Treatment duration was a mean (range) of 7.8 weeks (6.6-10.1). Maximum grade toxicity by type was first calculated including adverse events with treatment-attribution of possibly, probably or definitely related to either chemotherapy or radiation therapy. Serious and Other AEs were defined as grades 3-5 and grades 1-2, respectively, per CTCAEv3.
Gastrointestinal disorders Esophagitis	3.6% 1/28 • Participants were assessed weekly on treatment and at weeks 4 and 8 post treatment. Treatment duration was a mean (range) of 7.8 weeks (6.6-10.1). Maximum grade toxicity by type was first calculated including adverse events with treatment-attribution of possibly, probably or definitely related to either chemotherapy or radiation therapy. Serious and Other AEs were defined as grades 3-5 and grades 1-2, respectively, per CTCAEv3.
Gastrointestinal disorders Fistula, Pancreas	3.6% 1/28 • Participants were assessed weekly on treatment and at weeks 4 and 8 post treatment. Treatment duration was a mean (range) of 7.8 weeks (6.6-10.1). Maximum grade toxicity by type was first calculated including adverse events with treatment-attribution of possibly, probably or definitely related to either chemotherapy or radiation therapy. Serious and Other AEs were defined as grades 3-5 and grades 1-2, respectively, per CTCAEv3.
Gastrointestinal disorders Flatulence	3.6% 1/28 • Participants were assessed weekly on treatment and at weeks 4 and 8 post treatment. Treatment duration was a mean (range) of 7.8 weeks (6.6-10.1). Maximum grade toxicity by type was first calculated including adverse events with treatment-attribution of possibly, probably or definitely related to either chemotherapy or radiation therapy. Serious and Other AEs were defined as grades 3-5 and grades 1-2, respectively, per CTCAEv3.
Gastrointestinal disorders GI-other	10.7% 3/28 • Participants were assessed weekly on treatment and at weeks 4 and 8 post treatment. Treatment duration was a mean (range) of 7.8 weeks (6.6-10.1). Maximum grade toxicity by type was first calculated including adverse events with treatment-attribution of possibly, probably or definitely related to either chemotherapy or radiation therapy. Serious and Other AEs were defined as grades 3-5 and grades 1-2, respectively, per CTCAEv3.
Gastrointestinal disorders Hemorrhoids	3.6% 1/28 • Participants were assessed weekly on treatment and at weeks 4 and 8 post treatment. Treatment duration was a mean (range) of 7.8 weeks (6.6-10.1). Maximum grade toxicity by type was first calculated including adverse events with treatment-attribution of possibly, probably or definitely related to either chemotherapy or radiation therapy. Serious and Other AEs were defined as grades 3-5 and grades 1-2, respectively, per CTCAEv3.
Gastrointestinal disorders Muco/stomatitis by exam, oral cavity	32.1% 9/28 • Participants were assessed weekly on treatment and at weeks 4 and 8 post treatment. Treatment duration was a mean (range) of 7.8 weeks (6.6-10.1). Maximum grade toxicity by type was first calculated including adverse events with treatment-attribution of possibly, probably or definitely related to either chemotherapy or radiation therapy. Serious and Other AEs were defined as grades 3-5 and grades 1-2, respectively, per CTCAEv3.
Gastrointestinal disorders Muco/stomatitis by exam, stomach	3.6% 1/28 • Participants were assessed weekly on treatment and at weeks 4 and 8 post treatment. Treatment duration was a mean (range) of 7.8 weeks (6.6-10.1). Maximum grade toxicity by type was first calculated including adverse events with treatment-attribution of possibly, probably or definitely related to either chemotherapy or radiation therapy. Serious and Other AEs were defined as grades 3-5 and grades 1-2, respectively, per CTCAEv3.
Gastrointestinal disorders Nausea	89.3% 25/28 • Participants were assessed weekly on treatment and at weeks 4 and 8 post treatment. Treatment duration was a mean (range) of 7.8 weeks (6.6-10.1). Maximum grade toxicity by type was first calculated including adverse events with treatment-attribution of possibly, probably or definitely related to either chemotherapy or radiation therapy. Serious and Other AEs were defined as grades 3-5 and grades 1-2, respectively, per CTCAEv3.
Gastrointestinal disorders Oral cavity, pain	75.0% 21/28 • Participants were assessed weekly on treatment and at weeks 4 and 8 post treatment. Treatment duration was a mean (range) of 7.8 weeks (6.6-10.1). Maximum grade toxicity by type was first calculated including adverse events with treatment-attribution of possibly, probably or definitely related to either chemotherapy or radiation therapy. Serious and Other AEs were defined as grades 3-5 and grades 1-2, respectively, per CTCAEv3.
Gastrointestinal disorders Salivary	75.0% 21/28 • Participants were assessed weekly on treatment and at weeks 4 and 8 post treatment. Treatment duration was a mean (range) of 7.8 weeks (6.6-10.1). Maximum grade toxicity by type was first calculated including adverse events with treatment-attribution of possibly, probably or definitely related to either chemotherapy or radiation therapy. Serious and Other AEs were defined as grades 3-5 and grades 1-2, respectively, per CTCAEv3.
Gastrointestinal disorders Ulcer, duodenum	3.6% 1/28 • Participants were assessed weekly on treatment and at weeks 4 and 8 post treatment. Treatment duration was a mean (range) of 7.8 weeks (6.6-10.1). Maximum grade toxicity by type was first calculated including adverse events with treatment-attribution of possibly, probably or definitely related to either chemotherapy or radiation therapy. Serious and Other AEs were defined as grades 3-5 and grades 1-2, respectively, per CTCAEv3.
Gastrointestinal disorders Ulcer, small bowel NOS	3.6% 1/28 • Participants were assessed weekly on treatment and at weeks 4 and 8 post treatment. Treatment duration was a mean (range) of 7.8 weeks (6.6-10.1). Maximum grade toxicity by type was first calculated including adverse events with treatment-attribution of possibly, probably or definitely related to either chemotherapy or radiation therapy. Serious and Other AEs were defined as grades 3-5 and grades 1-2, respectively, per CTCAEv3.
Gastrointestinal disorders Vomiting	57.1% 16/28 • Participants were assessed weekly on treatment and at weeks 4 and 8 post treatment. Treatment duration was a mean (range) of 7.8 weeks (6.6-10.1). Maximum grade toxicity by type was first calculated including adverse events with treatment-attribution of possibly, probably or definitely related to either chemotherapy or radiation therapy. Serious and Other AEs were defined as grades 3-5 and grades 1-2, respectively, per CTCAEv3.
General disorders Edema head and neck	50.0% 14/28 • Participants were assessed weekly on treatment and at weeks 4 and 8 post treatment. Treatment duration was a mean (range) of 7.8 weeks (6.6-10.1). Maximum grade toxicity by type was first calculated including adverse events with treatment-attribution of possibly, probably or definitely related to either chemotherapy or radiation therapy. Serious and Other AEs were defined as grades 3-5 and grades 1-2, respectively, per CTCAEv3.
General disorders Edema limb	3.6% 1/28 • Participants were assessed weekly on treatment and at weeks 4 and 8 post treatment. Treatment duration was a mean (range) of 7.8 weeks (6.6-10.1). Maximum grade toxicity by type was first calculated including adverse events with treatment-attribution of possibly, probably or definitely related to either chemotherapy or radiation therapy. Serious and Other AEs were defined as grades 3-5 and grades 1-2, respectively, per CTCAEv3.
General disorders Edema trunk/genital	3.6% 1/28 • Participants were assessed weekly on treatment and at weeks 4 and 8 post treatment. Treatment duration was a mean (range) of 7.8 weeks (6.6-10.1). Maximum grade toxicity by type was first calculated including adverse events with treatment-attribution of possibly, probably or definitely related to either chemotherapy or radiation therapy. Serious and Other AEs were defined as grades 3-5 and grades 1-2, respectively, per CTCAEv3.
General disorders Fatigue	71.4% 20/28 • Participants were assessed weekly on treatment and at weeks 4 and 8 post treatment. Treatment duration was a mean (range) of 7.8 weeks (6.6-10.1). Maximum grade toxicity by type was first calculated including adverse events with treatment-attribution of possibly, probably or definitely related to either chemotherapy or radiation therapy. Serious and Other AEs were defined as grades 3-5 and grades 1-2, respectively, per CTCAEv3.
General disorders Fever w/o neutropenia	17.9% 5/28 • Participants were assessed weekly on treatment and at weeks 4 and 8 post treatment. Treatment duration was a mean (range) of 7.8 weeks (6.6-10.1). Maximum grade toxicity by type was first calculated including adverse events with treatment-attribution of possibly, probably or definitely related to either chemotherapy or radiation therapy. Serious and Other AEs were defined as grades 3-5 and grades 1-2, respectively, per CTCAEv3.
General disorders Injection site reaction	3.6% 1/28 • Participants were assessed weekly on treatment and at weeks 4 and 8 post treatment. Treatment duration was a mean (range) of 7.8 weeks (6.6-10.1). Maximum grade toxicity by type was first calculated including adverse events with treatment-attribution of possibly, probably or definitely related to either chemotherapy or radiation therapy. Serious and Other AEs were defined as grades 3-5 and grades 1-2, respectively, per CTCAEv3.
General disorders Pain-other	14.3% 4/28 • Participants were assessed weekly on treatment and at weeks 4 and 8 post treatment. Treatment duration was a mean (range) of 7.8 weeks (6.6-10.1). Maximum grade toxicity by type was first calculated including adverse events with treatment-attribution of possibly, probably or definitely related to either chemotherapy or radiation therapy. Serious and Other AEs were defined as grades 3-5 and grades 1-2, respectively, per CTCAEv3.
General disorders Rigors/chills	3.6% 1/28 • Participants were assessed weekly on treatment and at weeks 4 and 8 post treatment. Treatment duration was a mean (range) of 7.8 weeks (6.6-10.1). Maximum grade toxicity by type was first calculated including adverse events with treatment-attribution of possibly, probably or definitely related to either chemotherapy or radiation therapy. Serious and Other AEs were defined as grades 3-5 and grades 1-2, respectively, per CTCAEv3.
Hepatobiliary disorders Fistula, Biliary Treet	3.6% 1/28 • Participants were assessed weekly on treatment and at weeks 4 and 8 post treatment. Treatment duration was a mean (range) of 7.8 weeks (6.6-10.1). Maximum grade toxicity by type was first calculated including adverse events with treatment-attribution of possibly, probably or definitely related to either chemotherapy or radiation therapy. Serious and Other AEs were defined as grades 3-5 and grades 1-2, respectively, per CTCAEv3.
Immune system disorders Allergy-other	3.6% 1/28 • Participants were assessed weekly on treatment and at weeks 4 and 8 post treatment. Treatment duration was a mean (range) of 7.8 weeks (6.6-10.1). Maximum grade toxicity by type was first calculated including adverse events with treatment-attribution of possibly, probably or definitely related to either chemotherapy or radiation therapy. Serious and Other AEs were defined as grades 3-5 and grades 1-2, respectively, per CTCAEv3.
Infections and infestations Infection Gr0-2 neut, lung	3.6% 1/28 • Participants were assessed weekly on treatment and at weeks 4 and 8 post treatment. Treatment duration was a mean (range) of 7.8 weeks (6.6-10.1). Maximum grade toxicity by type was first calculated including adverse events with treatment-attribution of possibly, probably or definitely related to either chemotherapy or radiation therapy. Serious and Other AEs were defined as grades 3-5 and grades 1-2, respectively, per CTCAEv3.
Infections and infestations Infection Gr0-2 neut, oral cavity	10.7% 3/28 • Participants were assessed weekly on treatment and at weeks 4 and 8 post treatment. Treatment duration was a mean (range) of 7.8 weeks (6.6-10.1). Maximum grade toxicity by type was first calculated including adverse events with treatment-attribution of possibly, probably or definitely related to either chemotherapy or radiation therapy. Serious and Other AEs were defined as grades 3-5 and grades 1-2, respectively, per CTCAEv3.
Infections and infestations Infection Gr0-2 neut, skin	7.1% 2/28 • Participants were assessed weekly on treatment and at weeks 4 and 8 post treatment. Treatment duration was a mean (range) of 7.8 weeks (6.6-10.1). Maximum grade toxicity by type was first calculated including adverse events with treatment-attribution of possibly, probably or definitely related to either chemotherapy or radiation therapy. Serious and Other AEs were defined as grades 3-5 and grades 1-2, respectively, per CTCAEv3.
Infections and infestations Infection-other	57.1% 16/28 • Participants were assessed weekly on treatment and at weeks 4 and 8 post treatment. Treatment duration was a mean (range) of 7.8 weeks (6.6-10.1). Maximum grade toxicity by type was first calculated including adverse events with treatment-attribution of possibly, probably or definitely related to either chemotherapy or radiation therapy. Serious and Other AEs were defined as grades 3-5 and grades 1-2, respectively, per CTCAEv3.
Injury, poisoning and procedural complications Bruising	3.6% 1/28 • Participants were assessed weekly on treatment and at weeks 4 and 8 post treatment. Treatment duration was a mean (range) of 7.8 weeks (6.6-10.1). Maximum grade toxicity by type was first calculated including adverse events with treatment-attribution of possibly, probably or definitely related to either chemotherapy or radiation therapy. Serious and Other AEs were defined as grades 3-5 and grades 1-2, respectively, per CTCAEv3.
Injury, poisoning and procedural complications Chemoradiation dermatitis	64.3% 18/28 • Participants were assessed weekly on treatment and at weeks 4 and 8 post treatment. Treatment duration was a mean (range) of 7.8 weeks (6.6-10.1). Maximum grade toxicity by type was first calculated including adverse events with treatment-attribution of possibly, probably or definitely related to either chemotherapy or radiation therapy. Serious and Other AEs were defined as grades 3-5 and grades 1-2, respectively, per CTCAEv3.
Injury, poisoning and procedural complications Radiation dermatitis	3.6% 1/28 • Participants were assessed weekly on treatment and at weeks 4 and 8 post treatment. Treatment duration was a mean (range) of 7.8 weeks (6.6-10.1). Maximum grade toxicity by type was first calculated including adverse events with treatment-attribution of possibly, probably or definitely related to either chemotherapy or radiation therapy. Serious and Other AEs were defined as grades 3-5 and grades 1-2, respectively, per CTCAEv3.
Investigations Leukocytes	7.1% 2/28 • Participants were assessed weekly on treatment and at weeks 4 and 8 post treatment. Treatment duration was a mean (range) of 7.8 weeks (6.6-10.1). Maximum grade toxicity by type was first calculated including adverse events with treatment-attribution of possibly, probably or definitely related to either chemotherapy or radiation therapy. Serious and Other AEs were defined as grades 3-5 and grades 1-2, respectively, per CTCAEv3.
Investigations Neutrophils	14.3% 4/28 • Participants were assessed weekly on treatment and at weeks 4 and 8 post treatment. Treatment duration was a mean (range) of 7.8 weeks (6.6-10.1). Maximum grade toxicity by type was first calculated including adverse events with treatment-attribution of possibly, probably or definitely related to either chemotherapy or radiation therapy. Serious and Other AEs were defined as grades 3-5 and grades 1-2, respectively, per CTCAEv3.
Investigations Platelets	10.7% 3/28 • Participants were assessed weekly on treatment and at weeks 4 and 8 post treatment. Treatment duration was a mean (range) of 7.8 weeks (6.6-10.1). Maximum grade toxicity by type was first calculated including adverse events with treatment-attribution of possibly, probably or definitely related to either chemotherapy or radiation therapy. Serious and Other AEs were defined as grades 3-5 and grades 1-2, respectively, per CTCAEv3.
Investigations Weight loss	25.0% 7/28 • Participants were assessed weekly on treatment and at weeks 4 and 8 post treatment. Treatment duration was a mean (range) of 7.8 weeks (6.6-10.1). Maximum grade toxicity by type was first calculated including adverse events with treatment-attribution of possibly, probably or definitely related to either chemotherapy or radiation therapy. Serious and Other AEs were defined as grades 3-5 and grades 1-2, respectively, per CTCAEv3.
Metabolism and nutrition disorders Anorexia	14.3% 4/28 • Participants were assessed weekly on treatment and at weeks 4 and 8 post treatment. Treatment duration was a mean (range) of 7.8 weeks (6.6-10.1). Maximum grade toxicity by type was first calculated including adverse events with treatment-attribution of possibly, probably or definitely related to either chemotherapy or radiation therapy. Serious and Other AEs were defined as grades 3-5 and grades 1-2, respectively, per CTCAEv3.
Metabolism and nutrition disorders Dehydration	64.3% 18/28 • Participants were assessed weekly on treatment and at weeks 4 and 8 post treatment. Treatment duration was a mean (range) of 7.8 weeks (6.6-10.1). Maximum grade toxicity by type was first calculated including adverse events with treatment-attribution of possibly, probably or definitely related to either chemotherapy or radiation therapy. Serious and Other AEs were defined as grades 3-5 and grades 1-2, respectively, per CTCAEv3.
Metabolism and nutrition disorders Hyperglycemia	3.6% 1/28 • Participants were assessed weekly on treatment and at weeks 4 and 8 post treatment. Treatment duration was a mean (range) of 7.8 weeks (6.6-10.1). Maximum grade toxicity by type was first calculated including adverse events with treatment-attribution of possibly, probably or definitely related to either chemotherapy or radiation therapy. Serious and Other AEs were defined as grades 3-5 and grades 1-2, respectively, per CTCAEv3.
Metabolism and nutrition disorders Hyperkalemia	7.1% 2/28 • Participants were assessed weekly on treatment and at weeks 4 and 8 post treatment. Treatment duration was a mean (range) of 7.8 weeks (6.6-10.1). Maximum grade toxicity by type was first calculated including adverse events with treatment-attribution of possibly, probably or definitely related to either chemotherapy or radiation therapy. Serious and Other AEs were defined as grades 3-5 and grades 1-2, respectively, per CTCAEv3.
Metabolism and nutrition disorders Hypokalemia	3.6% 1/28 • Participants were assessed weekly on treatment and at weeks 4 and 8 post treatment. Treatment duration was a mean (range) of 7.8 weeks (6.6-10.1). Maximum grade toxicity by type was first calculated including adverse events with treatment-attribution of possibly, probably or definitely related to either chemotherapy or radiation therapy. Serious and Other AEs were defined as grades 3-5 and grades 1-2, respectively, per CTCAEv3.
Metabolism and nutrition disorders Hypomagnesemia	3.6% 1/28 • Participants were assessed weekly on treatment and at weeks 4 and 8 post treatment. Treatment duration was a mean (range) of 7.8 weeks (6.6-10.1). Maximum grade toxicity by type was first calculated including adverse events with treatment-attribution of possibly, probably or definitely related to either chemotherapy or radiation therapy. Serious and Other AEs were defined as grades 3-5 and grades 1-2, respectively, per CTCAEv3.
Metabolism and nutrition disorders Hyponatremia	3.6% 1/28 • Participants were assessed weekly on treatment and at weeks 4 and 8 post treatment. Treatment duration was a mean (range) of 7.8 weeks (6.6-10.1). Maximum grade toxicity by type was first calculated including adverse events with treatment-attribution of possibly, probably or definitely related to either chemotherapy or radiation therapy. Serious and Other AEs were defined as grades 3-5 and grades 1-2, respectively, per CTCAEv3.
Musculoskeletal and connective tissue disorders Back, pain	7.1% 2/28 • Participants were assessed weekly on treatment and at weeks 4 and 8 post treatment. Treatment duration was a mean (range) of 7.8 weeks (6.6-10.1). Maximum grade toxicity by type was first calculated including adverse events with treatment-attribution of possibly, probably or definitely related to either chemotherapy or radiation therapy. Serious and Other AEs were defined as grades 3-5 and grades 1-2, respectively, per CTCAEv3.
Musculoskeletal and connective tissue disorders Extremity-limb, pain	3.6% 1/28 • Participants were assessed weekly on treatment and at weeks 4 and 8 post treatment. Treatment duration was a mean (range) of 7.8 weeks (6.6-10.1). Maximum grade toxicity by type was first calculated including adverse events with treatment-attribution of possibly, probably or definitely related to either chemotherapy or radiation therapy. Serious and Other AEs were defined as grades 3-5 and grades 1-2, respectively, per CTCAEv3.
Musculoskeletal and connective tissue disorders Lymphedema-related fibrosis	3.6% 1/28 • Participants were assessed weekly on treatment and at weeks 4 and 8 post treatment. Treatment duration was a mean (range) of 7.8 weeks (6.6-10.1). Maximum grade toxicity by type was first calculated including adverse events with treatment-attribution of possibly, probably or definitely related to either chemotherapy or radiation therapy. Serious and Other AEs were defined as grades 3-5 and grades 1-2, respectively, per CTCAEv3.
Musculoskeletal and connective tissue disorders Neck, pain	3.6% 1/28 • Participants were assessed weekly on treatment and at weeks 4 and 8 post treatment. Treatment duration was a mean (range) of 7.8 weeks (6.6-10.1). Maximum grade toxicity by type was first calculated including adverse events with treatment-attribution of possibly, probably or definitely related to either chemotherapy or radiation therapy. Serious and Other AEs were defined as grades 3-5 and grades 1-2, respectively, per CTCAEv3.
Nervous system disorders Dizziness	3.6% 1/28 • Participants were assessed weekly on treatment and at weeks 4 and 8 post treatment. Treatment duration was a mean (range) of 7.8 weeks (6.6-10.1). Maximum grade toxicity by type was first calculated including adverse events with treatment-attribution of possibly, probably or definitely related to either chemotherapy or radiation therapy. Serious and Other AEs were defined as grades 3-5 and grades 1-2, respectively, per CTCAEv3.
Nervous system disorders Head/headache	7.1% 2/28 • Participants were assessed weekly on treatment and at weeks 4 and 8 post treatment. Treatment duration was a mean (range) of 7.8 weeks (6.6-10.1). Maximum grade toxicity by type was first calculated including adverse events with treatment-attribution of possibly, probably or definitely related to either chemotherapy or radiation therapy. Serious and Other AEs were defined as grades 3-5 and grades 1-2, respectively, per CTCAEv3.
Nervous system disorders Neuropathy CN IX pharynx ear tongue	3.6% 1/28 • Participants were assessed weekly on treatment and at weeks 4 and 8 post treatment. Treatment duration was a mean (range) of 7.8 weeks (6.6-10.1). Maximum grade toxicity by type was first calculated including adverse events with treatment-attribution of possibly, probably or definitely related to either chemotherapy or radiation therapy. Serious and Other AEs were defined as grades 3-5 and grades 1-2, respectively, per CTCAEv3.
Nervous system disorders Taste disturbance	89.3% 25/28 • Participants were assessed weekly on treatment and at weeks 4 and 8 post treatment. Treatment duration was a mean (range) of 7.8 weeks (6.6-10.1). Maximum grade toxicity by type was first calculated including adverse events with treatment-attribution of possibly, probably or definitely related to either chemotherapy or radiation therapy. Serious and Other AEs were defined as grades 3-5 and grades 1-2, respectively, per CTCAEv3.
Psychiatric disorders Agitation	3.6% 1/28 • Participants were assessed weekly on treatment and at weeks 4 and 8 post treatment. Treatment duration was a mean (range) of 7.8 weeks (6.6-10.1). Maximum grade toxicity by type was first calculated including adverse events with treatment-attribution of possibly, probably or definitely related to either chemotherapy or radiation therapy. Serious and Other AEs were defined as grades 3-5 and grades 1-2, respectively, per CTCAEv3.
Psychiatric disorders Anxiety	17.9% 5/28 • Participants were assessed weekly on treatment and at weeks 4 and 8 post treatment. Treatment duration was a mean (range) of 7.8 weeks (6.6-10.1). Maximum grade toxicity by type was first calculated including adverse events with treatment-attribution of possibly, probably or definitely related to either chemotherapy or radiation therapy. Serious and Other AEs were defined as grades 3-5 and grades 1-2, respectively, per CTCAEv3.
Psychiatric disorders Confusion	14.3% 4/28 • Participants were assessed weekly on treatment and at weeks 4 and 8 post treatment. Treatment duration was a mean (range) of 7.8 weeks (6.6-10.1). Maximum grade toxicity by type was first calculated including adverse events with treatment-attribution of possibly, probably or definitely related to either chemotherapy or radiation therapy. Serious and Other AEs were defined as grades 3-5 and grades 1-2, respectively, per CTCAEv3.
Psychiatric disorders Depression	17.9% 5/28 • Participants were assessed weekly on treatment and at weeks 4 and 8 post treatment. Treatment duration was a mean (range) of 7.8 weeks (6.6-10.1). Maximum grade toxicity by type was first calculated including adverse events with treatment-attribution of possibly, probably or definitely related to either chemotherapy or radiation therapy. Serious and Other AEs were defined as grades 3-5 and grades 1-2, respectively, per CTCAEv3.
Psychiatric disorders Insomnia	10.7% 3/28 • Participants were assessed weekly on treatment and at weeks 4 and 8 post treatment. Treatment duration was a mean (range) of 7.8 weeks (6.6-10.1). Maximum grade toxicity by type was first calculated including adverse events with treatment-attribution of possibly, probably or definitely related to either chemotherapy or radiation therapy. Serious and Other AEs were defined as grades 3-5 and grades 1-2, respectively, per CTCAEv3.
Renal and urinary disorders Urinary frequency/urgency	3.6% 1/28 • Participants were assessed weekly on treatment and at weeks 4 and 8 post treatment. Treatment duration was a mean (range) of 7.8 weeks (6.6-10.1). Maximum grade toxicity by type was first calculated including adverse events with treatment-attribution of possibly, probably or definitely related to either chemotherapy or radiation therapy. Serious and Other AEs were defined as grades 3-5 and grades 1-2, respectively, per CTCAEv3.
Respiratory, thoracic and mediastinal disorders Aspiration	3.6% 1/28 • Participants were assessed weekly on treatment and at weeks 4 and 8 post treatment. Treatment duration was a mean (range) of 7.8 weeks (6.6-10.1). Maximum grade toxicity by type was first calculated including adverse events with treatment-attribution of possibly, probably or definitely related to either chemotherapy or radiation therapy. Serious and Other AEs were defined as grades 3-5 and grades 1-2, respectively, per CTCAEv3.
Respiratory, thoracic and mediastinal disorders Cough	10.7% 3/28 • Participants were assessed weekly on treatment and at weeks 4 and 8 post treatment. Treatment duration was a mean (range) of 7.8 weeks (6.6-10.1). Maximum grade toxicity by type was first calculated including adverse events with treatment-attribution of possibly, probably or definitely related to either chemotherapy or radiation therapy. Serious and Other AEs were defined as grades 3-5 and grades 1-2, respectively, per CTCAEv3.
Respiratory, thoracic and mediastinal disorders Edema, larynx	3.6% 1/28 • Participants were assessed weekly on treatment and at weeks 4 and 8 post treatment. Treatment duration was a mean (range) of 7.8 weeks (6.6-10.1). Maximum grade toxicity by type was first calculated including adverse events with treatment-attribution of possibly, probably or definitely related to either chemotherapy or radiation therapy. Serious and Other AEs were defined as grades 3-5 and grades 1-2, respectively, per CTCAEv3.
Respiratory, thoracic and mediastinal disorders Pleura, pain	3.6% 1/28 • Participants were assessed weekly on treatment and at weeks 4 and 8 post treatment. Treatment duration was a mean (range) of 7.8 weeks (6.6-10.1). Maximum grade toxicity by type was first calculated including adverse events with treatment-attribution of possibly, probably or definitely related to either chemotherapy or radiation therapy. Serious and Other AEs were defined as grades 3-5 and grades 1-2, respectively, per CTCAEv3.
Respiratory, thoracic and mediastinal disorders Stenosis (incl anastomotic) pharynx	3.6% 1/28 • Participants were assessed weekly on treatment and at weeks 4 and 8 post treatment. Treatment duration was a mean (range) of 7.8 weeks (6.6-10.1). Maximum grade toxicity by type was first calculated including adverse events with treatment-attribution of possibly, probably or definitely related to either chemotherapy or radiation therapy. Serious and Other AEs were defined as grades 3-5 and grades 1-2, respectively, per CTCAEv3.
Respiratory, thoracic and mediastinal disorders Throat/pharynx/larynx, pain	25.0% 7/28 • Participants were assessed weekly on treatment and at weeks 4 and 8 post treatment. Treatment duration was a mean (range) of 7.8 weeks (6.6-10.1). Maximum grade toxicity by type was first calculated including adverse events with treatment-attribution of possibly, probably or definitely related to either chemotherapy or radiation therapy. Serious and Other AEs were defined as grades 3-5 and grades 1-2, respectively, per CTCAEv3.
Respiratory, thoracic and mediastinal disorders Voice changes/dysarthria	21.4% 6/28 • Participants were assessed weekly on treatment and at weeks 4 and 8 post treatment. Treatment duration was a mean (range) of 7.8 weeks (6.6-10.1). Maximum grade toxicity by type was first calculated including adverse events with treatment-attribution of possibly, probably or definitely related to either chemotherapy or radiation therapy. Serious and Other AEs were defined as grades 3-5 and grades 1-2, respectively, per CTCAEv3.
Skin and subcutaneous tissue disorders Alopecia	10.7% 3/28 • Participants were assessed weekly on treatment and at weeks 4 and 8 post treatment. Treatment duration was a mean (range) of 7.8 weeks (6.6-10.1). Maximum grade toxicity by type was first calculated including adverse events with treatment-attribution of possibly, probably or definitely related to either chemotherapy or radiation therapy. Serious and Other AEs were defined as grades 3-5 and grades 1-2, respectively, per CTCAEv3.
Skin and subcutaneous tissue disorders Dry skin	10.7% 3/28 • Participants were assessed weekly on treatment and at weeks 4 and 8 post treatment. Treatment duration was a mean (range) of 7.8 weeks (6.6-10.1). Maximum grade toxicity by type was first calculated including adverse events with treatment-attribution of possibly, probably or definitely related to either chemotherapy or radiation therapy. Serious and Other AEs were defined as grades 3-5 and grades 1-2, respectively, per CTCAEv3.
Skin and subcutaneous tissue disorders Erythema multiforme	17.9% 5/28 • Participants were assessed weekly on treatment and at weeks 4 and 8 post treatment. Treatment duration was a mean (range) of 7.8 weeks (6.6-10.1). Maximum grade toxicity by type was first calculated including adverse events with treatment-attribution of possibly, probably or definitely related to either chemotherapy or radiation therapy. Serious and Other AEs were defined as grades 3-5 and grades 1-2, respectively, per CTCAEv3.
Skin and subcutaneous tissue disorders Nail changes	14.3% 4/28 • Participants were assessed weekly on treatment and at weeks 4 and 8 post treatment. Treatment duration was a mean (range) of 7.8 weeks (6.6-10.1). Maximum grade toxicity by type was first calculated including adverse events with treatment-attribution of possibly, probably or definitely related to either chemotherapy or radiation therapy. Serious and Other AEs were defined as grades 3-5 and grades 1-2, respectively, per CTCAEv3.
Skin and subcutaneous tissue disorders Pruritus/itching	3.6% 1/28 • Participants were assessed weekly on treatment and at weeks 4 and 8 post treatment. Treatment duration was a mean (range) of 7.8 weeks (6.6-10.1). Maximum grade toxicity by type was first calculated including adverse events with treatment-attribution of possibly, probably or definitely related to either chemotherapy or radiation therapy. Serious and Other AEs were defined as grades 3-5 and grades 1-2, respectively, per CTCAEv3.
Skin and subcutaneous tissue disorders Rash/desquamation	14.3% 4/28 • Participants were assessed weekly on treatment and at weeks 4 and 8 post treatment. Treatment duration was a mean (range) of 7.8 weeks (6.6-10.1). Maximum grade toxicity by type was first calculated including adverse events with treatment-attribution of possibly, probably or definitely related to either chemotherapy or radiation therapy. Serious and Other AEs were defined as grades 3-5 and grades 1-2, respectively, per CTCAEv3.
Skin and subcutaneous tissue disorders Rash: acne/acneiform	17.9% 5/28 • Participants were assessed weekly on treatment and at weeks 4 and 8 post treatment. Treatment duration was a mean (range) of 7.8 weeks (6.6-10.1). Maximum grade toxicity by type was first calculated including adverse events with treatment-attribution of possibly, probably or definitely related to either chemotherapy or radiation therapy. Serious and Other AEs were defined as grades 3-5 and grades 1-2, respectively, per CTCAEv3.
Skin and subcutaneous tissue disorders Skin breakdown/decubitus ulcer	3.6% 1/28 • Participants were assessed weekly on treatment and at weeks 4 and 8 post treatment. Treatment duration was a mean (range) of 7.8 weeks (6.6-10.1). Maximum grade toxicity by type was first calculated including adverse events with treatment-attribution of possibly, probably or definitely related to either chemotherapy or radiation therapy. Serious and Other AEs were defined as grades 3-5 and grades 1-2, respectively, per CTCAEv3.
Skin and subcutaneous tissue disorders Skin-other	7.1% 2/28 • Participants were assessed weekly on treatment and at weeks 4 and 8 post treatment. Treatment duration was a mean (range) of 7.8 weeks (6.6-10.1). Maximum grade toxicity by type was first calculated including adverse events with treatment-attribution of possibly, probably or definitely related to either chemotherapy or radiation therapy. Serious and Other AEs were defined as grades 3-5 and grades 1-2, respectively, per CTCAEv3.
Skin and subcutaneous tissue disorders Ulceration	3.6% 1/28 • Participants were assessed weekly on treatment and at weeks 4 and 8 post treatment. Treatment duration was a mean (range) of 7.8 weeks (6.6-10.1). Maximum grade toxicity by type was first calculated including adverse events with treatment-attribution of possibly, probably or definitely related to either chemotherapy or radiation therapy. Serious and Other AEs were defined as grades 3-5 and grades 1-2, respectively, per CTCAEv3.
Vascular disorders Hypertension	3.6% 1/28 • Participants were assessed weekly on treatment and at weeks 4 and 8 post treatment. Treatment duration was a mean (range) of 7.8 weeks (6.6-10.1). Maximum grade toxicity by type was first calculated including adverse events with treatment-attribution of possibly, probably or definitely related to either chemotherapy or radiation therapy. Serious and Other AEs were defined as grades 3-5 and grades 1-2, respectively, per CTCAEv3.
Vascular disorders Hypotension	3.6% 1/28 • Participants were assessed weekly on treatment and at weeks 4 and 8 post treatment. Treatment duration was a mean (range) of 7.8 weeks (6.6-10.1). Maximum grade toxicity by type was first calculated including adverse events with treatment-attribution of possibly, probably or definitely related to either chemotherapy or radiation therapy. Serious and Other AEs were defined as grades 3-5 and grades 1-2, respectively, per CTCAEv3.

Additional Information

Roy B. Tishler, MD

Dana-Farber Cancer Institute

Phone: 617.632.5734

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place