Proton Radiotherapy With Chemotherapy for Nasopharyngeal Carcinoma

• Sponsor: Massachusetts General Hospital (Other)
• Overall Status: Completed
• CT.gov ID: NCT00592501
• Collaborator: Brigham and Women's Hospital (Other), Dana-Farber Cancer Institute (Other)
• Enrollment: 25
• Locations: 2
• Arm: 1
• Duration (Months): 150
• Patients Per Site: 12.5
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

Photon beam radiation is the standard type of radiation used to treat nasopharyngeal carcinoma. Photon beam radiation enters the body and passes through healthy tissue, encounters the tumor and leaves the body through healthy tissue. Proton beam radiation has been shown to have the same effect on tumors as photon beam radiation but it enters the body, passes through healthy tissue, and encounters the tumor but then stops. This means less healthy tissue is affected by proton beam treatment than by photon beam treatment. The purpose of this study is to determine the effectiveness of proton beam radiation in treating nasopharyngeal cancer and reducing the acute and long-term side effects from the treatment. This study will also test to see if the sparing of the healthy tissue can improve quality of life

Condition or Disease	Intervention/Treatment	Phase
Nasopharyngeal Carcinoma	Radiation: Proton/Photon Radiotherapy; Drug: Cisplatin; Drug: Fluorouracil	Phase 2

Detailed Description

• Before beginning study treatment, participants will be asked to fill out a Quality of Life (QOL) questionnaires, a Speech Assessment, a ChemoSensory Questionnaire, a Patient Swallowing Diary, A Swallowing Study, Salivary Tests and a Trismus Assessment. Participants will need to go to the Massachusetts Eye and Ear Infirmary (MEEI) or Massachusetts General Hospital (MGH) for these tests.

• Radiation therapy will be given once a day, five days a week, for seven weeks. This will be given as outpatient care at the Northeast Proton Therapy Center (proton component) and Massachusetts General Hospital (photon component).

• During radiation treatments, participants will receive cisplatin intravenously once every three weeks. This three-week period is called a cycle of treatment.

• After the completion of radiation, participants will receive cisplatin intravenously once every 4 weeks along with fluorouracil as a continuous infusion over 4 days starting on the day cisplatin is given, for three cycles.

• Participants will have a physical exam and blood work drawn weekly to monitor their health.

• An MR/CT scan of the head and neck will be done 2 months after the radiation treatment.

• Follow-up visits will occur once every three months for 2 years, then once every 6 months during years 3-5, then annually. During these follow-up visits, participants will have the following tests and procedures: physical examination; blood work; chest CT scan and CT/MRI of the head and neck will be repeated once every 6 months during the first three years; swallow study; salivary study; QOL questionnaires; speech assessment; ChemoSensory Questionnaire; and Trismus Assessment.

Study Design

• Study Type: Interventional
• Actual Enrollment: 25 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Study of Proton Radiotherapy With Chemotherapy for Nasopharyngeal Carcinoma
• Study Start Date: Oct 1, 2006
• Actual Primary Completion Date: Apr 1, 2019
• Actual Study Completion Date: Apr 1, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Proton/Photon Radiotherapy, Cisplatin, Fluorouracil	Radiation: Proton/Photon Radiotherapy; Given once a day, five days a week, for seven weeks.; Drug: Cisplatin; Given intravenously once every three weeks during radiation treatment, then once every four weeks for three cycles.; Drug: Fluorouracil; Given as continuous infusion over 4 days starting on the day cisplatin is received after radiation therapy.; Other Names: 5-FU

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Acute Toxicity [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.

2. Participant Compliance Rate to Assigned Treatment Intervention [2 years]

3. Sialometry to Evaluate Xerostomia (Dry Mouth) [Baseline and 2 years (24 months)]

   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.

4. Penetration-aspiration Scale to Evaluate Swallowing Function [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.

5. Serial Measurements of Maximal Inter-incisal Distance to Evaluate Trismus (Lockjaw) [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.

6. ChemoSensory Questionnaire (CSQ) to Evaluate Smell and Taste Function [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.

7. Number of Participants With Speech Problems Assessed by Head and Neck Health Status Assessment Inventory (HNHSAI) [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.

8. Health Related Quality-of-Life Outcomes Using Validated Quality-of-Life Instrument EORTC QLQ-C30 [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.

9. Health Related Quality-of-life Outcomes Using Validated Quality-of-life Instrument EORTC-QLQ-H&N [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.

Secondary Outcome Measures

1. Rate and Pattern of Locoregional Tumor Recurrence [3 years]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Biopsy proven greater than or equal to T2b and/or node positive non-metastatic, squamous cell carcinoma of the nasopharynx, types WHO I-III.

• No head and neck surgery of the primary tumor or lymph nodes except incisional or excisional biopsies.

• Zubrod performance status 0-1 or Karnofsky 70 or above.

• All patients must undergo pre-treatment evaluation of tumor extent and tumor measurement.

• Nutritional and general physical condition must be considered compatible with the proposed chemoradiation treatment

• Patients must have adequate platelet and renal function as outlined in protocol.

• 18 years of age or above.

• No active alcohol addiction.

• Women of childbearing potential must have a negative pregnancy test.

Exclusion Criteria:

• Stage IVC or evidence of distant metastases

• Previous irradiation for head and neck tumor

• Patient is on other experimental therapeutic cancer treatment

• Other malignancy except non-melanoma skin cancer or carcinomas of head and neck origin and have been controlled for at least 5 years.

• Active untreated infection

• Major medical or psychiatric illness

• Prophylactic use of amifostine or pilocarpine

• Pregnant or breast feeding women

• Symptomatic peripheral neuropathy of grade 2 or greater by NCI CTCAE

• Symptomatic altered hearing > grade 2 by CTCAE

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
2	Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02115

Sponsors and Collaborators

• Massachusetts General Hospital
• Brigham and Women's Hospital
• Dana-Farber Cancer Institute

Investigators

• Principal Investigator: Annie W Chan, MD, Massachusetts General Hospital

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jun 21, 2011
• Informed Consent Form - Feb 9, 2012

More Information

Publications

None provided.

• Responsible Party: Annie W. Chan, MD, Annie W. Chan, MD, Massachusetts General Hospital
• ClinicalTrials.gov Identifier: NCT00592501
• Other Study ID Numbers: 05-089
• First Posted: Jan 14, 2008
• Last Update Posted: Oct 26, 2021
• Last Verified: Oct 1, 2021

• Keywords provided by Annie W. Chan, MD, Annie W. Chan, MD, Massachusetts General Hospital: proton radiation; photon radiation; 5-FU; cisplatin
• Additional relevant MeSH terms: Carcinoma; Nasopharyngeal Carcinoma; Fluorouracil

Study Results

Participant Flow

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

Arm/Group Title	Proton/Photon Radiotherapy, Cisplatin, Fluorouracil
Arm/Group Description	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.
Period Title: Overall Study
STARTED	25
COMPLETED	23
NOT COMPLETED	2

Baseline Characteristics

Arm/Group Title	Proton/Photon Radiotherapy, Cisplatin, Fluorouracil
Arm/Group Description	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 Participants	23
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	21 91.3%
>=65 years	2 8.7%
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	48
Sex: Female, Male (Count of Participants)
Female	5 21.7%
Male	18 78.3%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	5 21.7%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	1 4.3%
White	14 60.9%
More than one race	0 0%
Unknown or Not Reported	3 13%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Acute Toxicity
Description	Acute toxicities are side affects that occur during treatment and 90 days after completion.
Time Frame	54 days of chemoradiation treatment and 90 days after completion, up to 144 days total

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Proton/Photon Radiotherapy, Cisplatin, Fluorouracil
Arm/Group Description	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.
Measure Participants	23
Count of Participants [Participants]	23 100%

2. Primary Outcome

Title	Participant Compliance Rate to Assigned Treatment Intervention
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Proton/Photon Radiotherapy, Cisplatin, Fluorouracil
Arm/Group Description	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.
Measure Participants	23
Received at least 2 cycles of concurrent chemotherapy	100 434.8%
Received at least 2 cycles of adjuvant chemotherapy	75 326.1%
Received 3 cycles of concurrent chemotherapy	83 360.9%

3. Primary Outcome

Title	Sialometry to Evaluate Xerostomia (Dry Mouth)
Description	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.
Time Frame	Baseline and 2 years (24 months)

Outcome Measure Data

Analysis Population Description

The mean values below are for all analyzed participants.

Arm/Group Title	Proton/Photon Radiotherapy, Cisplatin, Fluorouracil
Arm/Group Description	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.
Measure Participants	23
Unstimatulated saliva at baseline	1.89 (1.16)
Unstimulated saliva at 24 months	0.95 (0.57)

4. Primary Outcome

Title	Penetration-aspiration Scale to Evaluate Swallowing Function
Description	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.
Time Frame	Baseline and 12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Proton/Photon Radiotherapy, Cisplatin, Fluorouracil
Arm/Group Description	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.
Measure Participants	23
Penetration-aspiration scale at baseline	1.04
Penetration-aspiration scale at 12 months after radiation therapy	1.36

5. Primary Outcome

Title	Serial Measurements of Maximal Inter-incisal Distance to Evaluate Trismus (Lockjaw)
Description	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.
Time Frame	Baseline and 2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Proton/Photon Radiotherapy, Cisplatin, Fluorouracil
Arm/Group Description	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.
Measure Participants	23
Maximal inter-incisal distance at baseline	51.4 (5.5)
Maximal inter-incisal distance at 2 years	43.8 (6.8)

6. Primary Outcome

Title	ChemoSensory Questionnaire (CSQ) to Evaluate Smell and Taste Function
Description	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.
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Proton/Photon Radiotherapy, Cisplatin, Fluorouracil
Arm/Group Description	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.
Measure Participants	23
Taste score post-treatment	17 (1.05)
Smell score post-treatment	18 (1.06)

7. Primary Outcome

Title	Number of Participants With Speech Problems Assessed by Head and Neck Health Status Assessment Inventory (HNHSAI)
Description	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.
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Proton/Photon Radiotherapy, Cisplatin, Fluorouracil
Arm/Group Description	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.
Measure Participants	23
Number [participants]	0 0%

8. Primary Outcome

Title	Health Related Quality-of-Life Outcomes Using Validated Quality-of-Life Instrument EORTC QLQ-C30
Description	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.
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Proton/Photon Radiotherapy, Cisplatin, Fluorouracil
Arm/Group Description	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.
Measure Participants	23
Median (Standard Deviation) [Global Health Status score on a scale]	83 (20.9)

9. Primary Outcome

Title	Health Related Quality-of-life Outcomes Using Validated Quality-of-life Instrument EORTC-QLQ-H&N
Description	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.
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Proton/Photon Radiotherapy, Cisplatin, Fluorouracil
Arm/Group Description	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.
Measure Participants	23
Mean (Standard Error) [dry mouth score on a scale]	11.4 (3)

10. Secondary Outcome

Title	Rate and Pattern of Locoregional Tumor Recurrence
Time Frame	3 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Proton/Photon Radiotherapy, Cisplatin, Fluorouracil
Arm/Group Description	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.
Measure Participants	23
Local recurrence in high-dose region	2 8.7%
Distant recurrence	3 13%

Adverse Events

Time Frame	Toxicity evaluation occurred during protocol therapy and 5+ years of follow-up.
Adverse Event Reporting Description	Adverse events were routinely collected through regular investigator assessment and regular laboratory testing.
Arm/Group Title	Proton/Photon Radiotherapy, Cisplatin, Fluorouracil
Arm/Group Description	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.
All Cause Mortality
	Proton/Photon Radiotherapy, Cisplatin, Fluorouracil
	Affected / at Risk (%)	# Events
Total	6/23 (26.1%)
Serious Adverse Events
	Proton/Photon Radiotherapy, Cisplatin, Fluorouracil
	Affected / at Risk (%)	# Events
Total	1/23 (4.3%)
Blood and lymphatic system disorders
Blood/bone marrow	1/23 (4.3%)
Other (Not Including Serious) Adverse Events
	Proton/Photon Radiotherapy, Cisplatin, Fluorouracil
	Affected / at Risk (%)	# Events
Total	23/23 (100%)
Blood and lymphatic system disorders
Blood/Bone Marrow - Other	2/23 (8.7%)	2
Neutrophils	6/23 (26.1%)	8
Hemoglobin	13/23 (56.5%)	27
Hemorrhage/Bleeding - Other	1/23 (4.3%)	1
Leukocytes (total WBC)	9/23 (39.1%)	13
Lymphopenia	14/23 (60.9%)	20
Blood/Bone Marrow - Other	1/23 (4.3%)	1
platelets	7/23 (30.4%)	9
Cardiac disorders
Cardiac troponin T (cTnT)	1/23 (4.3%)	1
Hypertension	1/23 (4.3%)	1
Hypotension	3/23 (13%)	3
Vasovagal episode	1/23 (4.3%)	1
Ear and labyrinth disorders
Hearing: patients with/without baseline audiogram and enrolled in a monitoring program	15/23 (65.2%)	21
Auditory/Ear - Other	1/23 (4.3%)	1
Tinnitus	14/23 (60.9%)	29
Endocrine disorders
Thyroid function, high (hyperthyroidism, thyrotoxicosis)	1/23 (4.3%)	1
Thyroid function, low (hypothyroidism)	2/23 (8.7%)	2
Eye disorders
Vision-blurred vision	4/23 (17.4%)	4
Ophthalmoplegia/ diplopia (double vision)	1/23 (4.3%)	1
Gastrointestinal disorders
Abdominal pain	3/23 (13%)	4
Gastrointestinal - Other	1/23 (4.3%)	1
Anorexia	21/23 (91.3%)	37
Constipation	12/23 (52.2%)	19
Salivary gland changes/saliva	17/23 (73.9%)	25
Dehydration	15/23 (65.2%)	25
Diarrhea	8/23 (34.8%)	10
Dry mouth/salivary gland (xerostomia)	20/23 (87%)	35
Taste alteration (dysgeusia)	20/23 (87%)	33
Heartburn/dyspepsia	7/23 (30.4%)	7
Dysphagia (difficulty swallowing)	22/23 (95.7%)	61
Gastrointestinal - Other	1/23 (4.3%)	1
Ileus, GI	1/23 (4.3%)	1
Mucositis/stomatitis - oral cavity	17/23 (73.9%)	38
Mucositis/stomatitis - pharynx	15/23 (65.2%)	34
Nausea	21/23 (91.3%)	55
Gastrointestinal - Other	9/23 (39.1%)	18
Dry mouth/salivary gland (xerostomia)	11/23 (47.8%)	22
Vomiting	19/23 (82.6%)	33
Gastrointestinal - Other	1/23 (4.3%)	1
General disorders
Constitutional Symptoms - Other	1/23 (4.3%)	2
Constitutional Symptoms - Other	1/23 (4.3%)	1
Rigors/chills	4/23 (17.4%)	4
Lymphatics - other	3/23 (13%)	3
Edema: head and neck	5/23 (21.7%)	5
Edema: limb	2/23 (8.7%)	3
Fatigue (asthenia, lethargy, malaise)	22/23 (95.7%)	63
Fever	5/23 (21.7%)	5
Pain - head/headache	9/23 (39.1%)	13
Insomnia	6/23 (26.1%)	10
Pain - extremity-limb	2/23 (8.7%)	4
Constitutional Symptoms - Other	19/23 (82.6%)	36
Pain: oral-gums	7/23 (30.4%)	15
Pain NOS	4/23 (17.4%)	7
Pain - other	3/23 (13%)	3
pain - anus	1/23 (4.3%)	1
pain - back	3/23 (13%)	3
pain - other	1/23 (4.3%)	1
pain - face	1/23 (4.3%)	1
pain - eye	1/23 (4.3%)	1
pain - middle ear	1/23 (4.3%)	1
pain - neck	1/23 (4.3%)	1
pain - chest wall	1/23 (4.3%)	1
pain - oral cavity	5/23 (21.7%)	9
pain - throat/pharynx/larynx	15/23 (65.2%)	22
pain - joint	3/23 (13%)	3
weight loss	22/23 (95.7%)	49
Sweating (diaphoresis)	2/23 (8.7%)	2
Constitutional Symptoms - Other	1/23 (4.3%)	1
Infections and infestations
Infection - lung (pneumonia)	4/23 (17.4%)	4
Infection - other	8/23 (34.8%)	13
Infections - skin (cellulitis)	1/23 (4.3%)	1
Febrile neutropenia	1/23 (4.3%)	1
Colitis, infectious (e.g., Clostridium difficile)	1/23 (4.3%)	1
Infection - Middle ear (otitis media)	3/23 (13%)	3
infection - bronchus	1/23 (4.3%)	1
infection - upper airway NOS	1/23 (4.3%)	1
Infection - Other	1/23 (4.3%)	2
Metabolism and nutrition disorders
Alkaline phosphatase	2/23 (8.7%)	2
ALT, SGPT	4/23 (17.4%)	7
AST, SGOT	2/23 (8.7%)	2
Bicarbonate, serum-low	1/23 (4.3%)	1
Calcium, serum-high (hypercalcemia)	1/23 (4.3%)	1
Glucose, serum-high (hyperglycemia)	6/23 (26.1%)	11
Potassium, serum-low (hypokalemia)	4/23 (17.4%)	4
Magnesium, serum-low (hypomagnesemia)	4/23 (17.4%)	5
Sodium, serum-low (hyponatremia)	5/23 (21.7%)	8
Metabolic/Laboratory - Other	1/23 (4.3%)	1
Magnesium, serum-high (hypermagnesemia)	1/23 (4.3%)	2
Potassium, serum-high (hyperkalemia)	2/23 (8.7%)	2
Sodium, serum-high (hypernatremia)	1/23 (4.3%)	1
Musculoskeletal and connective tissue disorders
Arthritis (non-septic)	1/23 (4.3%)	1
Musculoskeletal/Soft Tissue - Other	2/23 (8.7%)	2
Trismus (difficulty, restriction or pain when opening mouth)	9/23 (39.1%)	12
Musculoskeletal/Soft Tissue - Other	1/23 (4.3%)	1
Nervous system disorders
CNS necrosis/cystic progression	2/23 (8.7%)	2
Confusion	3/23 (13%)	4
Mood alteration - Depression	8/23 (34.8%)	10
Dizziness	12/23 (52.2%)	21
Neurology - other	1/23 (4.3%)	1
Extrapyramidal/ involuntary movement/restlessness	1/23 (4.3%)	1
Neuropathy: sensory	7/23 (30.4%)	8
Memory impairment	1/23 (4.3%)	1
Neurology - Other	5/23 (21.7%)	5
Apnea	1/23 (4.3%)	1
neurology - other	2/23 (8.7%)	2
Syncope (fainting)	2/23 (8.7%)	2
Somnolence/depressed level of consciousness	4/23 (17.4%)	5
Speech impairment (e.g., dysphasia or aphasia)	1/23 (4.3%)	1
Psychiatric disorders
Anxiety	11/23 (47.8%)	22
Renal and urinary disorders
Renal failure	2/23 (8.7%)	2
Renal/Genitourinary - Other	1/23 (4.3%)	1
Respiratory, thoracic and mediastinal disorders
Aspiration	2/23 (8.7%)	2
Cough	6/23 (26.1%)	6
Voice changes/dysarthria	3/23 (13%)	4
Dyspnea (shortness of breath)	2/23 (8.7%)	2
Hemorrhage, pulmonary/upper respiratory - nose	2/23 (8.7%)	2
Hiccoughs (hiccups, singultus)	6/23 (26.1%)	6
Hypoxia	2/23 (8.7%)	2
Pulmonary/Upper Respiratory - Other	14/23 (60.9%)	25
Pulmonary/Upper Respiratory - Other	2/23 (8.7%)	2
Pulmonary/Upper Respiratory - Other	1/23 (4.3%)	1
Pulmonary/Upper Respiratory - Other	1/23 (4.3%)	1
Skin and subcutaneous tissue disorders
Alopecia	10/23 (43.5%)	10
Bruising	2/23 (8.7%)	2
Rash/desquamation	3/23 (13%)	4
Dermatology/Skin - Other	9/23 (39.1%)	11
Rash: hand-foot skin reaction	2/23 (8.7%)	2
Hyperpigmentation	13/23 (56.5%)	13
Hypopigmentation	1/23 (4.3%)	1
Injection site reaction/extravasation changes	2/23 (8.7%)	2
Pruritus/itching	2/23 (8.7%)	2
Dermatology/Skin - Other	1/23 (4.3%)	1
Dermatology/Skin --Other	2/23 (8.7%)	2
Dermatology/Skin - Other	13/23 (56.5%)	28
Rash: dermatitis associated with radiation	8/23 (34.8%)	14
Vascular disorders
Thrombosis/thrombus/embolism	1/23 (4.3%)	1
Thrombosis/thrombus/embolism	1/23 (4.3%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.