Trial Outcomes & Findings for Proton Radiotherapy With Chemotherapy for Nasopharyngeal Carcinoma (NCT NCT00592501)

NCT ID: NCT00592501

Last Updated: 2021-10-26

Results Overview

Acute toxicities are side affects that occur during treatment and 90 days after completion.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 25 participants
• Primary outcome timeframe: 54 days of chemoradiation treatment and 90 days after completion, up to 144 days total
• Results posted on: 2021-10-26

Participant Flow

Study period: 2006 and 2011 Location: Outpatient clinic at the Massachusetts General Hospital

Participant milestones

Measure	Proton/Photon Radiotherapy, Cisplatin, Fluorouracil Proton/Photon Radiotherapy: Given once a day, five days a week, for seven weeks. Cisplatin: Given intravenously once every three weeks during radiation treatment, then once every four weeks for three cycles. Fluorouracil: Given as continuous infusion over 4 days starting on the day cisplatin is received after radiation therapy.
Overall Study STARTED	25
Overall Study COMPLETED	23
Overall Study NOT COMPLETED	2

Reasons for withdrawal

Measure	Proton/Photon Radiotherapy, Cisplatin, Fluorouracil Proton/Photon Radiotherapy: Given once a day, five days a week, for seven weeks. Cisplatin: Given intravenously once every three weeks during radiation treatment, then once every four weeks for three cycles. Fluorouracil: Given as continuous infusion over 4 days starting on the day cisplatin is received after radiation therapy.
Overall Study Withdrawal by Subject	1
Overall Study Participant found to have metastatic disease after enrollment thus deemed ineligible	1

Baseline Characteristics

Proton Radiotherapy With Chemotherapy for Nasopharyngeal Carcinoma

Baseline characteristics by cohort

Measure	Proton/Photon Radiotherapy, Cisplatin, Fluorouracil n=23 Participants Proton/Photon Radiotherapy: Given once a day, five days a week, for seven weeks. Cisplatin: Given intravenously once every three weeks during radiation treatment, then once every four weeks for three cycles. Fluorouracil: Given as continuous infusion over 4 days starting on the day cisplatin is received after radiation therapy.
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	21 Participants n=5 Participants
Age, Categorical >=65 years	2 Participants n=5 Participants
Age, Continuous	48 years n=5 Participants
Sex: Female, Male Female	5 Participants n=5 Participants
Sex: Female, Male Male	18 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	5 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants
Race (NIH/OMB) White	14 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	3 Participants n=5 Participants

PRIMARY outcome

Timeframe: 54 days of chemoradiation treatment and 90 days after completion, up to 144 days total

Acute toxicities are side affects that occur during treatment and 90 days after completion.

Outcome measures

Measure	Proton/Photon Radiotherapy, Cisplatin, Fluorouracil n=23 Participants Proton/Photon Radiotherapy: Given once a day, five days a week, for seven weeks. Cisplatin: Given intravenously once every three weeks during radiation treatment, then once every four weeks for three cycles. Fluorouracil: Given as continuous infusion over 4 days starting on the day cisplatin is received after radiation therapy.
Number of Participants With Acute Toxicity	23 Participants

PRIMARY outcome

Timeframe: 2 years

Outcome measures

Measure	Proton/Photon Radiotherapy, Cisplatin, Fluorouracil n=23 Participants Proton/Photon Radiotherapy: Given once a day, five days a week, for seven weeks. Cisplatin: Given intravenously once every three weeks during radiation treatment, then once every four weeks for three cycles. Fluorouracil: Given as continuous infusion over 4 days starting on the day cisplatin is received after radiation therapy.
Participant Compliance Rate to Assigned Treatment Intervention Received at least 2 cycles of concurrent chemotherapy	100 percentage of participants
Participant Compliance Rate to Assigned Treatment Intervention Received at least 2 cycles of adjuvant chemotherapy	75 percentage of participants
Participant Compliance Rate to Assigned Treatment Intervention Received 3 cycles of concurrent chemotherapy	83 percentage of participants

PRIMARY outcome

Timeframe: Baseline and 2 years (24 months)

Population: The mean values below are for all analyzed participants.

Sialometry is a measure of saliva flow. The normal daily production of saliva varies between 0.5 and 1.5 liters. Stimulated saliva is produced in response to a mechanical, gustatory, olfactory, or pharmacological stimulus, contributing to around 40-50% of daily salivary production. In adults, normal total stimulated salivary flow ranges 1-3 mL/minute, low ranges 0.7-1.0 mL/minute, while hyposalivation is characterized by a stimulated salivary flow <0.7mL/minute.

Outcome measures

Measure	Proton/Photon Radiotherapy, Cisplatin, Fluorouracil n=23 Participants Proton/Photon Radiotherapy: Given once a day, five days a week, for seven weeks. Cisplatin: Given intravenously once every three weeks during radiation treatment, then once every four weeks for three cycles. Fluorouracil: Given as continuous infusion over 4 days starting on the day cisplatin is received after radiation therapy.
Sialometry to Evaluate Xerostomia (Dry Mouth) Unstimatulated saliva at baseline	1.89 milliliters Standard Deviation 1.16
Sialometry to Evaluate Xerostomia (Dry Mouth) Unstimulated saliva at 24 months	0.95 milliliters Standard Deviation 0.57

PRIMARY outcome

Timeframe: Baseline and 12 months

The videofluoroscopic swallow study (VFSS) is the gold standard diagnostic tool to evaluate oropharyngeal dysphagia. The penetration-aspiration scale (PAS) is an 8-point scale used to grade the severity of penetration or aspiration observed in a videofluoroscopic swallow study. Aspiration is defined as the passing of the bolus below the true vocal folds, and penetration is when the bolus enters the airway but not below the true vocal folds. 1 is normal, no penetration or aspiration. 2-5 is penetration. 6-8 is aspiration.

Outcome measures

Measure	Proton/Photon Radiotherapy, Cisplatin, Fluorouracil n=23 Participants Proton/Photon Radiotherapy: Given once a day, five days a week, for seven weeks. Cisplatin: Given intravenously once every three weeks during radiation treatment, then once every four weeks for three cycles. Fluorouracil: Given as continuous infusion over 4 days starting on the day cisplatin is received after radiation therapy.
Penetration-aspiration Scale to Evaluate Swallowing Function Penetration-aspiration scale at baseline	1.04 score on a scale Interval 1.0 to 2.0
Penetration-aspiration Scale to Evaluate Swallowing Function Penetration-aspiration scale at 12 months after radiation therapy	1.36 score on a scale Interval 1.0 to 5.0

PRIMARY outcome

Timeframe: Baseline and 2 years

Serial measures of the changes of the maximal inter-incisal distance in the vertical opening, right lateral, and left lateral jaw movements are used to evaluate trismus (lockjaw). An average measurement of the three directional areas will be reported.

Outcome measures

Measure	Proton/Photon Radiotherapy, Cisplatin, Fluorouracil n=23 Participants Proton/Photon Radiotherapy: Given once a day, five days a week, for seven weeks. Cisplatin: Given intravenously once every three weeks during radiation treatment, then once every four weeks for three cycles. Fluorouracil: Given as continuous infusion over 4 days starting on the day cisplatin is received after radiation therapy.
Serial Measurements of Maximal Inter-incisal Distance to Evaluate Trismus (Lockjaw) Maximal inter-incisal distance at baseline	51.4 millimeters Standard Deviation 5.5
Serial Measurements of Maximal Inter-incisal Distance to Evaluate Trismus (Lockjaw) Maximal inter-incisal distance at 2 years	43.8 millimeters Standard Deviation 6.8

PRIMARY outcome

Timeframe: 2 years

The Chemosensory Questionnaire (CSQ) has four questions each on smell and taste. A minimum score of 4 and a maximum of 20 for the smell scale and taste scale are possible with a higher score indicating better function.

Outcome measures

Measure	Proton/Photon Radiotherapy, Cisplatin, Fluorouracil n=23 Participants Proton/Photon Radiotherapy: Given once a day, five days a week, for seven weeks. Cisplatin: Given intravenously once every three weeks during radiation treatment, then once every four weeks for three cycles. Fluorouracil: Given as continuous infusion over 4 days starting on the day cisplatin is received after radiation therapy.
ChemoSensory Questionnaire (CSQ) to Evaluate Smell and Taste Function Taste score post-treatment	17 score on a scale Standard Error 1.05
ChemoSensory Questionnaire (CSQ) to Evaluate Smell and Taste Function Smell score post-treatment	18 score on a scale Standard Error 1.06

PRIMARY outcome

Timeframe: 2 years

The Head and Neck Health Status Assessment Inventory (HNHSAI) is a descriptive outcome assessment consisting of 14 yes/no questions to measure number of participants with speech problems.

Outcome measures

Measure	Proton/Photon Radiotherapy, Cisplatin, Fluorouracil n=23 Participants Proton/Photon Radiotherapy: Given once a day, five days a week, for seven weeks. Cisplatin: Given intravenously once every three weeks during radiation treatment, then once every four weeks for three cycles. Fluorouracil: Given as continuous infusion over 4 days starting on the day cisplatin is received after radiation therapy.
Number of Participants With Speech Problems Assessed by Head and Neck Health Status Assessment Inventory (HNHSAI)	0 participants

PRIMARY outcome

Timeframe: 2 years

General quality of life is measured with the European organization for research and treatment of cancer (EORTC) quality of life questionnaire (QLQ) EORTC QLQ-C30 (cancer 30). They are self-administered questionnaires. All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level. A high score for the global health status / QoL represents a high QoL.

Outcome measures

Measure	Proton/Photon Radiotherapy, Cisplatin, Fluorouracil n=23 Participants Proton/Photon Radiotherapy: Given once a day, five days a week, for seven weeks. Cisplatin: Given intravenously once every three weeks during radiation treatment, then once every four weeks for three cycles. Fluorouracil: Given as continuous infusion over 4 days starting on the day cisplatin is received after radiation therapy.
Health Related Quality-of-Life Outcomes Using Validated Quality-of-Life Instrument EORTC QLQ-C30	83 Global Health Status score on a scale Standard Deviation 20.9

PRIMARY outcome

Timeframe: 2 years

General quality of life is measured with the European organization for research and treatment of cancer (EORTC) quality of life questionnaires (QLQ) for head and neck (H&N) (EORTC-QLQ-H&N). The head & neck cancer module incorporates seven multi-item scales that assess pain, swallowing, senses (taste and smell), speech, social eating, social contact, and sexuality. There are also eleven single items. All of the scales and single-item measures range in score from 0 to 100. For all items and symptom scales, high scores represent a high level of symptomatology/problems.

Outcome measures

Measure	Proton/Photon Radiotherapy, Cisplatin, Fluorouracil n=23 Participants Proton/Photon Radiotherapy: Given once a day, five days a week, for seven weeks. Cisplatin: Given intravenously once every three weeks during radiation treatment, then once every four weeks for three cycles. Fluorouracil: Given as continuous infusion over 4 days starting on the day cisplatin is received after radiation therapy.
Health Related Quality-of-life Outcomes Using Validated Quality-of-life Instrument EORTC-QLQ-H&N	11.4 dry mouth score on a scale Standard Error 3

SECONDARY outcome

Timeframe: 3 years

Outcome measures

Measure	Proton/Photon Radiotherapy, Cisplatin, Fluorouracil n=23 Participants Proton/Photon Radiotherapy: Given once a day, five days a week, for seven weeks. Cisplatin: Given intravenously once every three weeks during radiation treatment, then once every four weeks for three cycles. Fluorouracil: Given as continuous infusion over 4 days starting on the day cisplatin is received after radiation therapy.
Rate and Pattern of Locoregional Tumor Recurrence Local recurrence in high-dose region	2 participants
Rate and Pattern of Locoregional Tumor Recurrence Distant recurrence	3 participants

Adverse Events

Proton/Photon Radiotherapy, Cisplatin, Fluorouracil

Serious events: 1 serious events

Other events: 23 other events

Deaths: 6 deaths

Serious adverse events

Measure

Proton/Photon Radiotherapy, Cisplatin, Fluorouracil n=23 participants at risk Proton/Photon Radiotherapy: Given once a day, five days a week, for seven weeks. Cisplatin: Given intravenously once every three weeks during radiation treatment, then once every four weeks for three cycles. Fluorouracil: Given as continuous infusion over 4 days starting on the day cisplatin is received after radiation therapy.

Blood and lymphatic system disorders Blood/bone marrow

4.3% 1/23 • Toxicity evaluation occurred during protocol therapy and 5+ years of follow-up. Adverse events were routinely collected through regular investigator assessment and regular laboratory testing.

Other adverse events

Measure	Proton/Photon Radiotherapy, Cisplatin, Fluorouracil n=23 participants at risk Proton/Photon Radiotherapy: Given once a day, five days a week, for seven weeks. Cisplatin: Given intravenously once every three weeks during radiation treatment, then once every four weeks for three cycles. Fluorouracil: Given as continuous infusion over 4 days starting on the day cisplatin is received after radiation therapy.
Infections and infestations Febrile neutropenia	4.3% 1/23 • Number of events 1 • Toxicity evaluation occurred during protocol therapy and 5+ years of follow-up. Adverse events were routinely collected through regular investigator assessment and regular laboratory testing.
General disorders Fever	21.7% 5/23 • Number of events 5 • Toxicity evaluation occurred during protocol therapy and 5+ years of follow-up. Adverse events were routinely collected through regular investigator assessment and regular laboratory testing.
Nervous system disorders Neuropathy: sensory	30.4% 7/23 • Number of events 8 • Toxicity evaluation occurred during protocol therapy and 5+ years of follow-up. Adverse events were routinely collected through regular investigator assessment and regular laboratory testing.
Gastrointestinal disorders Gastrointestinal - Other	4.3% 1/23 • Number of events 1 • Toxicity evaluation occurred during protocol therapy and 5+ years of follow-up. Adverse events were routinely collected through regular investigator assessment and regular laboratory testing.
Metabolism and nutrition disorders Glucose, serum-high (hyperglycemia)	26.1% 6/23 • Number of events 11 • Toxicity evaluation occurred during protocol therapy and 5+ years of follow-up. Adverse events were routinely collected through regular investigator assessment and regular laboratory testing.
Ear and labyrinth disorders Hearing: patients with/without baseline audiogram and enrolled in a monitoring program	65.2% 15/23 • Number of events 21 • Toxicity evaluation occurred during protocol therapy and 5+ years of follow-up. Adverse events were routinely collected through regular investigator assessment and regular laboratory testing.
Blood and lymphatic system disorders Hemorrhage/Bleeding - Other	4.3% 1/23 • Number of events 1 • Toxicity evaluation occurred during protocol therapy and 5+ years of follow-up. Adverse events were routinely collected through regular investigator assessment and regular laboratory testing.
Respiratory, thoracic and mediastinal disorders Hiccoughs (hiccups, singultus)	26.1% 6/23 • Number of events 6 • Toxicity evaluation occurred during protocol therapy and 5+ years of follow-up. Adverse events were routinely collected through regular investigator assessment and regular laboratory testing.
Skin and subcutaneous tissue disorders Hyperpigmentation	56.5% 13/23 • Number of events 13 • Toxicity evaluation occurred during protocol therapy and 5+ years of follow-up. Adverse events were routinely collected through regular investigator assessment and regular laboratory testing.
Cardiac disorders Hypertension	4.3% 1/23 • Number of events 1 • Toxicity evaluation occurred during protocol therapy and 5+ years of follow-up. Adverse events were routinely collected through regular investigator assessment and regular laboratory testing.
Endocrine disorders Thyroid function, high (hyperthyroidism, thyrotoxicosis)	4.3% 1/23 • Number of events 1 • Toxicity evaluation occurred during protocol therapy and 5+ years of follow-up. Adverse events were routinely collected through regular investigator assessment and regular laboratory testing.
Metabolism and nutrition disorders Potassium, serum-low (hypokalemia)	17.4% 4/23 • Number of events 4 • Toxicity evaluation occurred during protocol therapy and 5+ years of follow-up. Adverse events were routinely collected through regular investigator assessment and regular laboratory testing.
Metabolism and nutrition disorders Magnesium, serum-low (hypomagnesemia)	17.4% 4/23 • Number of events 5 • Toxicity evaluation occurred during protocol therapy and 5+ years of follow-up. Adverse events were routinely collected through regular investigator assessment and regular laboratory testing.
Metabolism and nutrition disorders Sodium, serum-low (hyponatremia)	21.7% 5/23 • Number of events 8 • Toxicity evaluation occurred during protocol therapy and 5+ years of follow-up. Adverse events were routinely collected through regular investigator assessment and regular laboratory testing.
Skin and subcutaneous tissue disorders Hypopigmentation	4.3% 1/23 • Number of events 1 • Toxicity evaluation occurred during protocol therapy and 5+ years of follow-up. Adverse events were routinely collected through regular investigator assessment and regular laboratory testing.
Cardiac disorders Hypotension	13.0% 3/23 • Number of events 3 • Toxicity evaluation occurred during protocol therapy and 5+ years of follow-up. Adverse events were routinely collected through regular investigator assessment and regular laboratory testing.
Endocrine disorders Thyroid function, low (hypothyroidism)	8.7% 2/23 • Number of events 2 • Toxicity evaluation occurred during protocol therapy and 5+ years of follow-up. Adverse events were routinely collected through regular investigator assessment and regular laboratory testing.
Respiratory, thoracic and mediastinal disorders Hypoxia	8.7% 2/23 • Number of events 2 • Toxicity evaluation occurred during protocol therapy and 5+ years of follow-up. Adverse events were routinely collected through regular investigator assessment and regular laboratory testing.
Gastrointestinal disorders Ileus, GI	4.3% 1/23 • Number of events 1 • Toxicity evaluation occurred during protocol therapy and 5+ years of follow-up. Adverse events were routinely collected through regular investigator assessment and regular laboratory testing.
Metabolism and nutrition disorders Metabolic/Laboratory - Other	4.3% 1/23 • Number of events 1 • Toxicity evaluation occurred during protocol therapy and 5+ years of follow-up. Adverse events were routinely collected through regular investigator assessment and regular laboratory testing.
Infections and infestations Colitis, infectious (e.g., Clostridium difficile)	4.3% 1/23 • Number of events 1 • Toxicity evaluation occurred during protocol therapy and 5+ years of follow-up. Adverse events were routinely collected through regular investigator assessment and regular laboratory testing.
Skin and subcutaneous tissue disorders Rash: hand-foot skin reaction	8.7% 2/23 • Number of events 2 • Toxicity evaluation occurred during protocol therapy and 5+ years of follow-up. Adverse events were routinely collected through regular investigator assessment and regular laboratory testing.
General disorders Pain - head/headache	39.1% 9/23 • Number of events 13 • Toxicity evaluation occurred during protocol therapy and 5+ years of follow-up. Adverse events were routinely collected through regular investigator assessment and regular laboratory testing.
General disorders Constitutional Symptoms - Other	4.3% 1/23 • Number of events 1 • Toxicity evaluation occurred during protocol therapy and 5+ years of follow-up. Adverse events were routinely collected through regular investigator assessment and regular laboratory testing.
Gastrointestinal disorders Abdominal pain	13.0% 3/23 • Number of events 4 • Toxicity evaluation occurred during protocol therapy and 5+ years of follow-up. Adverse events were routinely collected through regular investigator assessment and regular laboratory testing.
Blood and lymphatic system disorders Blood/Bone Marrow - Other	4.3% 1/23 • Number of events 1 • Toxicity evaluation occurred during protocol therapy and 5+ years of follow-up. Adverse events were routinely collected through regular investigator assessment and regular laboratory testing.
Renal and urinary disorders Renal failure	8.7% 2/23 • Number of events 2 • Toxicity evaluation occurred during protocol therapy and 5+ years of follow-up. Adverse events were routinely collected through regular investigator assessment and regular laboratory testing.
Metabolism and nutrition disorders Alkaline phosphatase	8.7% 2/23 • Number of events 2 • Toxicity evaluation occurred during protocol therapy and 5+ years of follow-up. Adverse events were routinely collected through regular investigator assessment and regular laboratory testing.
Skin and subcutaneous tissue disorders Alopecia	43.5% 10/23 • Number of events 10 • Toxicity evaluation occurred during protocol therapy and 5+ years of follow-up. Adverse events were routinely collected through regular investigator assessment and regular laboratory testing.
Metabolism and nutrition disorders ALT, SGPT	17.4% 4/23 • Number of events 7 • Toxicity evaluation occurred during protocol therapy and 5+ years of follow-up. Adverse events were routinely collected through regular investigator assessment and regular laboratory testing.
Blood and lymphatic system disorders Neutrophils	26.1% 6/23 • Number of events 8 • Toxicity evaluation occurred during protocol therapy and 5+ years of follow-up. Adverse events were routinely collected through regular investigator assessment and regular laboratory testing.
Blood and lymphatic system disorders Hemoglobin	56.5% 13/23 • Number of events 27 • Toxicity evaluation occurred during protocol therapy and 5+ years of follow-up. Adverse events were routinely collected through regular investigator assessment and regular laboratory testing.
Gastrointestinal disorders Anorexia	91.3% 21/23 • Number of events 37 • Toxicity evaluation occurred during protocol therapy and 5+ years of follow-up. Adverse events were routinely collected through regular investigator assessment and regular laboratory testing.
Psychiatric disorders Anxiety	47.8% 11/23 • Number of events 22 • Toxicity evaluation occurred during protocol therapy and 5+ years of follow-up. Adverse events were routinely collected through regular investigator assessment and regular laboratory testing.
Musculoskeletal and connective tissue disorders Arthritis (non-septic)	4.3% 1/23 • Number of events 1 • Toxicity evaluation occurred during protocol therapy and 5+ years of follow-up. Adverse events were routinely collected through regular investigator assessment and regular laboratory testing.
Respiratory, thoracic and mediastinal disorders Aspiration	8.7% 2/23 • Number of events 2 • Toxicity evaluation occurred during protocol therapy and 5+ years of follow-up. Adverse events were routinely collected through regular investigator assessment and regular laboratory testing.
Infections and infestations Infection - lung (pneumonia)	17.4% 4/23 • Number of events 4 • Toxicity evaluation occurred during protocol therapy and 5+ years of follow-up. Adverse events were routinely collected through regular investigator assessment and regular laboratory testing.
Metabolism and nutrition disorders AST, SGOT	8.7% 2/23 • Number of events 2 • Toxicity evaluation occurred during protocol therapy and 5+ years of follow-up. Adverse events were routinely collected through regular investigator assessment and regular laboratory testing.
Metabolism and nutrition disorders Bicarbonate, serum-low	4.3% 1/23 • Number of events 1 • Toxicity evaluation occurred during protocol therapy and 5+ years of follow-up. Adverse events were routinely collected through regular investigator assessment and regular laboratory testing.
Eye disorders Vision-blurred vision	17.4% 4/23 • Number of events 4 • Toxicity evaluation occurred during protocol therapy and 5+ years of follow-up. Adverse events were routinely collected through regular investigator assessment and regular laboratory testing.
Skin and subcutaneous tissue disorders Bruising	8.7% 2/23 • Number of events 2 • Toxicity evaluation occurred during protocol therapy and 5+ years of follow-up. Adverse events were routinely collected through regular investigator assessment and regular laboratory testing.
Metabolism and nutrition disorders Calcium, serum-high (hypercalcemia)	4.3% 1/23 • Number of events 1 • Toxicity evaluation occurred during protocol therapy and 5+ years of follow-up. Adverse events were routinely collected through regular investigator assessment and regular laboratory testing.
Infections and infestations Infection - other	34.8% 8/23 • Number of events 13 • Toxicity evaluation occurred during protocol therapy and 5+ years of follow-up. Adverse events were routinely collected through regular investigator assessment and regular laboratory testing.
Cardiac disorders Cardiac troponin T (cTnT)	4.3% 1/23 • Number of events 1 • Toxicity evaluation occurred during protocol therapy and 5+ years of follow-up. Adverse events were routinely collected through regular investigator assessment and regular laboratory testing.
Infections and infestations Infections - skin (cellulitis)	4.3% 1/23 • Number of events 1 • Toxicity evaluation occurred during protocol therapy and 5+ years of follow-up. Adverse events were routinely collected through regular investigator assessment and regular laboratory testing.
General disorders Rigors/chills	17.4% 4/23 • Number of events 4 • Toxicity evaluation occurred during protocol therapy and 5+ years of follow-up. Adverse events were routinely collected through regular investigator assessment and regular laboratory testing.
Nervous system disorders CNS necrosis/cystic progression	8.7% 2/23 • Number of events 2 • Toxicity evaluation occurred during protocol therapy and 5+ years of follow-up. Adverse events were routinely collected through regular investigator assessment and regular laboratory testing.
Nervous system disorders Confusion	13.0% 3/23 • Number of events 4 • Toxicity evaluation occurred during protocol therapy and 5+ years of follow-up. Adverse events were routinely collected through regular investigator assessment and regular laboratory testing.
Gastrointestinal disorders Constipation	52.2% 12/23 • Number of events 19 • Toxicity evaluation occurred during protocol therapy and 5+ years of follow-up. Adverse events were routinely collected through regular investigator assessment and regular laboratory testing.
Gastrointestinal disorders Salivary gland changes/saliva	73.9% 17/23 • Number of events 25 • Toxicity evaluation occurred during protocol therapy and 5+ years of follow-up. Adverse events were routinely collected through regular investigator assessment and regular laboratory testing.
Respiratory, thoracic and mediastinal disorders Cough	26.1% 6/23 • Number of events 6 • Toxicity evaluation occurred during protocol therapy and 5+ years of follow-up. Adverse events were routinely collected through regular investigator assessment and regular laboratory testing.
Gastrointestinal disorders Dehydration	65.2% 15/23 • Number of events 25 • Toxicity evaluation occurred during protocol therapy and 5+ years of follow-up. Adverse events were routinely collected through regular investigator assessment and regular laboratory testing.
Nervous system disorders Mood alteration - Depression	34.8% 8/23 • Number of events 10 • Toxicity evaluation occurred during protocol therapy and 5+ years of follow-up. Adverse events were routinely collected through regular investigator assessment and regular laboratory testing.
Skin and subcutaneous tissue disorders Rash/desquamation	13.0% 3/23 • Number of events 4 • Toxicity evaluation occurred during protocol therapy and 5+ years of follow-up. Adverse events were routinely collected through regular investigator assessment and regular laboratory testing.
Gastrointestinal disorders Diarrhea	34.8% 8/23 • Number of events 10 • Toxicity evaluation occurred during protocol therapy and 5+ years of follow-up. Adverse events were routinely collected through regular investigator assessment and regular laboratory testing.
Nervous system disorders Dizziness	52.2% 12/23 • Number of events 21 • Toxicity evaluation occurred during protocol therapy and 5+ years of follow-up. Adverse events were routinely collected through regular investigator assessment and regular laboratory testing.
Eye disorders Ophthalmoplegia/ diplopia (double vision)	4.3% 1/23 • Number of events 1 • Toxicity evaluation occurred during protocol therapy and 5+ years of follow-up. Adverse events were routinely collected through regular investigator assessment and regular laboratory testing.
Gastrointestinal disorders Dry mouth/salivary gland (xerostomia)	47.8% 11/23 • Number of events 22 • Toxicity evaluation occurred during protocol therapy and 5+ years of follow-up. Adverse events were routinely collected through regular investigator assessment and regular laboratory testing.
Vascular disorders Thrombosis/thrombus/embolism	4.3% 1/23 • Number of events 1 • Toxicity evaluation occurred during protocol therapy and 5+ years of follow-up. Adverse events were routinely collected through regular investigator assessment and regular laboratory testing.
Respiratory, thoracic and mediastinal disorders Voice changes/dysarthria	13.0% 3/23 • Number of events 4 • Toxicity evaluation occurred during protocol therapy and 5+ years of follow-up. Adverse events were routinely collected through regular investigator assessment and regular laboratory testing.
Gastrointestinal disorders Taste alteration (dysgeusia)	87.0% 20/23 • Number of events 33 • Toxicity evaluation occurred during protocol therapy and 5+ years of follow-up. Adverse events were routinely collected through regular investigator assessment and regular laboratory testing.
Nervous system disorders Neurology - other	4.3% 1/23 • Number of events 1 • Toxicity evaluation occurred during protocol therapy and 5+ years of follow-up. Adverse events were routinely collected through regular investigator assessment and regular laboratory testing.
Gastrointestinal disorders Heartburn/dyspepsia	30.4% 7/23 • Number of events 7 • Toxicity evaluation occurred during protocol therapy and 5+ years of follow-up. Adverse events were routinely collected through regular investigator assessment and regular laboratory testing.
Gastrointestinal disorders Dysphagia (difficulty swallowing)	95.7% 22/23 • Number of events 61 • Toxicity evaluation occurred during protocol therapy and 5+ years of follow-up. Adverse events were routinely collected through regular investigator assessment and regular laboratory testing.
Respiratory, thoracic and mediastinal disorders Dyspnea (shortness of breath)	8.7% 2/23 • Number of events 2 • Toxicity evaluation occurred during protocol therapy and 5+ years of follow-up. Adverse events were routinely collected through regular investigator assessment and regular laboratory testing.
General disorders Lymphatics - other	13.0% 3/23 • Number of events 3 • Toxicity evaluation occurred during protocol therapy and 5+ years of follow-up. Adverse events were routinely collected through regular investigator assessment and regular laboratory testing.
General disorders Edema: head and neck	21.7% 5/23 • Number of events 5 • Toxicity evaluation occurred during protocol therapy and 5+ years of follow-up. Adverse events were routinely collected through regular investigator assessment and regular laboratory testing.
General disorders Edema: limb	8.7% 2/23 • Number of events 3 • Toxicity evaluation occurred during protocol therapy and 5+ years of follow-up. Adverse events were routinely collected through regular investigator assessment and regular laboratory testing.
Respiratory, thoracic and mediastinal disorders Hemorrhage, pulmonary/upper respiratory - nose	8.7% 2/23 • Number of events 2 • Toxicity evaluation occurred during protocol therapy and 5+ years of follow-up. Adverse events were routinely collected through regular investigator assessment and regular laboratory testing.
Skin and subcutaneous tissue disorders Dermatology/Skin - Other	56.5% 13/23 • Number of events 28 • Toxicity evaluation occurred during protocol therapy and 5+ years of follow-up. Adverse events were routinely collected through regular investigator assessment and regular laboratory testing.
Nervous system disorders Extrapyramidal/ involuntary movement/restlessness	4.3% 1/23 • Number of events 1 • Toxicity evaluation occurred during protocol therapy and 5+ years of follow-up. Adverse events were routinely collected through regular investigator assessment and regular laboratory testing.
General disorders Fatigue (asthenia, lethargy, malaise)	95.7% 22/23 • Number of events 63 • Toxicity evaluation occurred during protocol therapy and 5+ years of follow-up. Adverse events were routinely collected through regular investigator assessment and regular laboratory testing.
Gastrointestinal disorders Mucositis/stomatitis - oral cavity	73.9% 17/23 • Number of events 38 • Toxicity evaluation occurred during protocol therapy and 5+ years of follow-up. Adverse events were routinely collected through regular investigator assessment and regular laboratory testing.
Skin and subcutaneous tissue disorders Injection site reaction/extravasation changes	8.7% 2/23 • Number of events 2 • Toxicity evaluation occurred during protocol therapy and 5+ years of follow-up. Adverse events were routinely collected through regular investigator assessment and regular laboratory testing.
General disorders Insomnia	26.1% 6/23 • Number of events 10 • Toxicity evaluation occurred during protocol therapy and 5+ years of follow-up. Adverse events were routinely collected through regular investigator assessment and regular laboratory testing.
Ear and labyrinth disorders Auditory/Ear - Other	4.3% 1/23 • Number of events 1 • Toxicity evaluation occurred during protocol therapy and 5+ years of follow-up. Adverse events were routinely collected through regular investigator assessment and regular laboratory testing.
Ear and labyrinth disorders Tinnitus	60.9% 14/23 • Number of events 29 • Toxicity evaluation occurred during protocol therapy and 5+ years of follow-up. Adverse events were routinely collected through regular investigator assessment and regular laboratory testing.
General disorders Pain - extremity-limb	8.7% 2/23 • Number of events 4 • Toxicity evaluation occurred during protocol therapy and 5+ years of follow-up. Adverse events were routinely collected through regular investigator assessment and regular laboratory testing.
Blood and lymphatic system disorders Leukocytes (total WBC)	39.1% 9/23 • Number of events 13 • Toxicity evaluation occurred during protocol therapy and 5+ years of follow-up. Adverse events were routinely collected through regular investigator assessment and regular laboratory testing.
Blood and lymphatic system disorders Lymphopenia	60.9% 14/23 • Number of events 20 • Toxicity evaluation occurred during protocol therapy and 5+ years of follow-up. Adverse events were routinely collected through regular investigator assessment and regular laboratory testing.
Metabolism and nutrition disorders Magnesium, serum-high (hypermagnesemia)	4.3% 1/23 • Number of events 2 • Toxicity evaluation occurred during protocol therapy and 5+ years of follow-up. Adverse events were routinely collected through regular investigator assessment and regular laboratory testing.
Nervous system disorders Memory impairment	4.3% 1/23 • Number of events 1 • Toxicity evaluation occurred during protocol therapy and 5+ years of follow-up. Adverse events were routinely collected through regular investigator assessment and regular laboratory testing.
Gastrointestinal disorders Mucositis/stomatitis - pharynx	65.2% 15/23 • Number of events 34 • Toxicity evaluation occurred during protocol therapy and 5+ years of follow-up. Adverse events were routinely collected through regular investigator assessment and regular laboratory testing.
Respiratory, thoracic and mediastinal disorders Pulmonary/Upper Respiratory - Other	4.3% 1/23 • Number of events 1 • Toxicity evaluation occurred during protocol therapy and 5+ years of follow-up. Adverse events were routinely collected through regular investigator assessment and regular laboratory testing.
Gastrointestinal disorders Nausea	91.3% 21/23 • Number of events 55 • Toxicity evaluation occurred during protocol therapy and 5+ years of follow-up. Adverse events were routinely collected through regular investigator assessment and regular laboratory testing.
Musculoskeletal and connective tissue disorders Musculoskeletal/Soft Tissue - Other	4.3% 1/23 • Number of events 1 • Toxicity evaluation occurred during protocol therapy and 5+ years of follow-up. Adverse events were routinely collected through regular investigator assessment and regular laboratory testing.
Nervous system disorders Neurology - Other	21.7% 5/23 • Number of events 5 • Toxicity evaluation occurred during protocol therapy and 5+ years of follow-up. Adverse events were routinely collected through regular investigator assessment and regular laboratory testing.
Nervous system disorders Apnea	4.3% 1/23 • Number of events 1 • Toxicity evaluation occurred during protocol therapy and 5+ years of follow-up. Adverse events were routinely collected through regular investigator assessment and regular laboratory testing.
General disorders Pain: oral-gums	30.4% 7/23 • Number of events 15 • Toxicity evaluation occurred during protocol therapy and 5+ years of follow-up. Adverse events were routinely collected through regular investigator assessment and regular laboratory testing.
Infections and infestations Infection - Middle ear (otitis media)	13.0% 3/23 • Number of events 3 • Toxicity evaluation occurred during protocol therapy and 5+ years of follow-up. Adverse events were routinely collected through regular investigator assessment and regular laboratory testing.
General disorders Pain NOS	17.4% 4/23 • Number of events 7 • Toxicity evaluation occurred during protocol therapy and 5+ years of follow-up. Adverse events were routinely collected through regular investigator assessment and regular laboratory testing.
General disorders Pain - other	13.0% 3/23 • Number of events 3 • Toxicity evaluation occurred during protocol therapy and 5+ years of follow-up. Adverse events were routinely collected through regular investigator assessment and regular laboratory testing.
General disorders pain - anus	4.3% 1/23 • Number of events 1 • Toxicity evaluation occurred during protocol therapy and 5+ years of follow-up. Adverse events were routinely collected through regular investigator assessment and regular laboratory testing.
General disorders pain - back	13.0% 3/23 • Number of events 3 • Toxicity evaluation occurred during protocol therapy and 5+ years of follow-up. Adverse events were routinely collected through regular investigator assessment and regular laboratory testing.
General disorders pain - other	4.3% 1/23 • Number of events 1 • Toxicity evaluation occurred during protocol therapy and 5+ years of follow-up. Adverse events were routinely collected through regular investigator assessment and regular laboratory testing.
General disorders pain - face	4.3% 1/23 • Number of events 1 • Toxicity evaluation occurred during protocol therapy and 5+ years of follow-up. Adverse events were routinely collected through regular investigator assessment and regular laboratory testing.
General disorders pain - eye	4.3% 1/23 • Number of events 1 • Toxicity evaluation occurred during protocol therapy and 5+ years of follow-up. Adverse events were routinely collected through regular investigator assessment and regular laboratory testing.
General disorders pain - middle ear	4.3% 1/23 • Number of events 1 • Toxicity evaluation occurred during protocol therapy and 5+ years of follow-up. Adverse events were routinely collected through regular investigator assessment and regular laboratory testing.
General disorders pain - neck	4.3% 1/23 • Number of events 1 • Toxicity evaluation occurred during protocol therapy and 5+ years of follow-up. Adverse events were routinely collected through regular investigator assessment and regular laboratory testing.
General disorders pain - chest wall	4.3% 1/23 • Number of events 1 • Toxicity evaluation occurred during protocol therapy and 5+ years of follow-up. Adverse events were routinely collected through regular investigator assessment and regular laboratory testing.
General disorders pain - oral cavity	21.7% 5/23 • Number of events 9 • Toxicity evaluation occurred during protocol therapy and 5+ years of follow-up. Adverse events were routinely collected through regular investigator assessment and regular laboratory testing.
General disorders pain - throat/pharynx/larynx	65.2% 15/23 • Number of events 22 • Toxicity evaluation occurred during protocol therapy and 5+ years of follow-up. Adverse events were routinely collected through regular investigator assessment and regular laboratory testing.
Nervous system disorders neurology - other	8.7% 2/23 • Number of events 2 • Toxicity evaluation occurred during protocol therapy and 5+ years of follow-up. Adverse events were routinely collected through regular investigator assessment and regular laboratory testing.
Blood and lymphatic system disorders platelets	30.4% 7/23 • Number of events 9 • Toxicity evaluation occurred during protocol therapy and 5+ years of follow-up. Adverse events were routinely collected through regular investigator assessment and regular laboratory testing.
Infections and infestations infection - bronchus	4.3% 1/23 • Number of events 1 • Toxicity evaluation occurred during protocol therapy and 5+ years of follow-up. Adverse events were routinely collected through regular investigator assessment and regular laboratory testing.
General disorders pain - joint	13.0% 3/23 • Number of events 3 • Toxicity evaluation occurred during protocol therapy and 5+ years of follow-up. Adverse events were routinely collected through regular investigator assessment and regular laboratory testing.
Metabolism and nutrition disorders Potassium, serum-high (hyperkalemia)	8.7% 2/23 • Number of events 2 • Toxicity evaluation occurred during protocol therapy and 5+ years of follow-up. Adverse events were routinely collected through regular investigator assessment and regular laboratory testing.
Skin and subcutaneous tissue disorders Pruritus/itching	8.7% 2/23 • Number of events 2 • Toxicity evaluation occurred during protocol therapy and 5+ years of follow-up. Adverse events were routinely collected through regular investigator assessment and regular laboratory testing.
General disorders weight loss	95.7% 22/23 • Number of events 49 • Toxicity evaluation occurred during protocol therapy and 5+ years of follow-up. Adverse events were routinely collected through regular investigator assessment and regular laboratory testing.
Cardiac disorders Vasovagal episode	4.3% 1/23 • Number of events 1 • Toxicity evaluation occurred during protocol therapy and 5+ years of follow-up. Adverse events were routinely collected through regular investigator assessment and regular laboratory testing.
Musculoskeletal and connective tissue disorders Trismus (difficulty, restriction or pain when opening mouth)	39.1% 9/23 • Number of events 12 • Toxicity evaluation occurred during protocol therapy and 5+ years of follow-up. Adverse events were routinely collected through regular investigator assessment and regular laboratory testing.
Infections and infestations infection - upper airway NOS	4.3% 1/23 • Number of events 1 • Toxicity evaluation occurred during protocol therapy and 5+ years of follow-up. Adverse events were routinely collected through regular investigator assessment and regular laboratory testing.
Gastrointestinal disorders Vomiting	82.6% 19/23 • Number of events 33 • Toxicity evaluation occurred during protocol therapy and 5+ years of follow-up. Adverse events were routinely collected through regular investigator assessment and regular laboratory testing.
Nervous system disorders Syncope (fainting)	8.7% 2/23 • Number of events 2 • Toxicity evaluation occurred during protocol therapy and 5+ years of follow-up. Adverse events were routinely collected through regular investigator assessment and regular laboratory testing.
Metabolism and nutrition disorders Sodium, serum-high (hypernatremia)	4.3% 1/23 • Number of events 1 • Toxicity evaluation occurred during protocol therapy and 5+ years of follow-up. Adverse events were routinely collected through regular investigator assessment and regular laboratory testing.
Nervous system disorders Somnolence/depressed level of consciousness	17.4% 4/23 • Number of events 5 • Toxicity evaluation occurred during protocol therapy and 5+ years of follow-up. Adverse events were routinely collected through regular investigator assessment and regular laboratory testing.
General disorders Sweating (diaphoresis)	8.7% 2/23 • Number of events 2 • Toxicity evaluation occurred during protocol therapy and 5+ years of follow-up. Adverse events were routinely collected through regular investigator assessment and regular laboratory testing.
Nervous system disorders Speech impairment (e.g., dysphasia or aphasia)	4.3% 1/23 • Number of events 1 • Toxicity evaluation occurred during protocol therapy and 5+ years of follow-up. Adverse events were routinely collected through regular investigator assessment and regular laboratory testing.
Skin and subcutaneous tissue disorders Dermatology/Skin --Other	8.7% 2/23 • Number of events 2 • Toxicity evaluation occurred during protocol therapy and 5+ years of follow-up. Adverse events were routinely collected through regular investigator assessment and regular laboratory testing.
Renal and urinary disorders Renal/Genitourinary - Other	4.3% 1/23 • Number of events 1 • Toxicity evaluation occurred during protocol therapy and 5+ years of follow-up. Adverse events were routinely collected through regular investigator assessment and regular laboratory testing.
Infections and infestations Infection - Other	4.3% 1/23 • Number of events 2 • Toxicity evaluation occurred during protocol therapy and 5+ years of follow-up. Adverse events were routinely collected through regular investigator assessment and regular laboratory testing.
Skin and subcutaneous tissue disorders Rash: dermatitis associated with radiation	34.8% 8/23 • Number of events 14 • Toxicity evaluation occurred during protocol therapy and 5+ years of follow-up. Adverse events were routinely collected through regular investigator assessment and regular laboratory testing.

Additional Information

Annie W. Chan, MD

Massachusetts General Hospital

Phone: 617-726-5184

Email: AWCHAN@PARTNERS.ORG

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place