Sulfasalazine in Preventing Acute Diarrhea in Patients Wi... | NCT01198145

NCT01198145

ID	Type	Description	Link
NCI-2011-02602	Registry Identifier	CTRP (Clinical Trials Reporting System)
CDR0000684240	Registry Identifier	PDQ (Physician Data Query)

Status Module

Sponsor/Collaborators Module

Name	Class
National Cancer Institute (NCI)	NIH

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Arm I: Sulfasalazine	Experimental	Patients receive oral sulfasalazine twice daily during radiotherapy and for 4 weeks after completion of radiotherapy.	Drug: sulfasalazine
Arm II: Placebo	Placebo Comparator	Patients receive oral placebo twice daily during radiotherapy and for 4 weeks after completion of radiotherapy.	Other: placebo

Name	Type	Description	Arm Group Labels	Other Names
sulfasalazine	Drug	Given orally	Arm I: Sulfasalazine
placebo

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Maximum Severity of Diarrhea Toxicity as Measured by the CTCAE v4.0 During and After Radiotherapy (RT)	The primary endpoint for this study is the maximal severity of diarrhea toxicity. Severity of diarrhea was graded using the terminology and grading categories defined in the NCI's Common Toxicity Criteria (CTCAE), Version 4.0. Grade 0 = None; 1=Mild; Grade 2=Moderate, Grade 3=Severe, Grade 4=Life-threatening as measured by the CTCAE version 4.0. Assessments were recorded during the course of RT and for 6 weeks following RT. The table below represents the worst graded diarrhea for each patient. A two-sided Wilcoxon rank-sum test will be used to test the equality of the distributions of maximum diarrhea severity grades between the two treatment arms.	During radiation therapy and up to 6 weeks post radiation therapy

Secondary Outcomes

Measure	Description	Time Frame
Maximum Severity of Each Outcome Variable (Rectal Bleeding, Abdominal Cramping, Tenesmus, Constipation, and Diarrhea) Measured During and After RT	The maximal severity of each of 5 different adverse even types (Tenesmus, Abdominal Pain, Constipation, Diarrhea, and Rectal Bleeding) were collected as a secondary endpoint. Severity of the events was graded using the terminology and grading categories defined in the NCI's Common Toxicity Criteria (CTCAE), Version 4.0. Grade 0 = None; 1=Mild; Grade 2=Moderate, Grade 3=Severe, Grade 4=Life-threatening. Adverse events were assessed during the course of RT and for 6 weeks following RT. The table below represents the worst grade for each patient for each type. Two-sided chi-square tests will be used to compare each percentage variable between treatment arms for each event type.

Eligibility Module

Eligibility Criteria

DISEASE CHARACTERISTICS:

Diagnosis of cancer that supports the use of radiotherapy to the pelvis
No current or prior metastases beyond pelvic regional lymph nodes
Planning to receive a course of continuous definitive or adjuvant external-beam radiotherapy to a minimum dose of 4500 cGy with or without fluorouracil, capecitabine, or oxaliplatin
Planned course of pelvic radiotherapy must fall within the following parameters:
- Pelvis must be encompassed by the planned radiotherapy fields
  - Superior border may not lie superior to the L4-5 interspace and may not be inferior to the most inferior aspect of the sacroiliac joints
  - Portions of the rectum may have special blocking, depending upon disease site
- Total planned dose to the central axis midplane (for AP-PA parallel opposed fields) or isocenter (for 3- or 4-field techniques) for the pelvic field must lie between 4500-5300 cGy (inclusive)*
  - Subsequent to completion of treatment to the pelvic field, a boost to primary tumor or tumor bed may be planned
- Planned treatment is to be given 4-5 times per week on a one-treatment-per-day basis
  - Daily dose (specified at central axis midplane or at isocenter for multi-field techniques) must lie between 170-210 cGy (inclusive) per day*
NOTE: *For institutions that do not use midplane or isocenter as the point for specification of dose, it will be necessary to determine the dose according to the methods specified above in order to determine patient eligibility.
No perineal irradiation planned (e.g., anal cancer patients, patients who have had an abdominal-perineal resection)
No brachytherapy planned before the completion of all external-beam radiotherapy
No planned split-course radiotherapy

PATIENT CHARACTERISTICS:

ECOG performance status 0-2
Life expectancy ≥ 6 months
Hemoglobin ≥ 10.0 g/dL
Leukocytes ≥ 3,500/mm^3
ANC ≥ 1,500/mm^3
Platelet count ≥ 100,000/mm^3
Creatinine ≤ 1.5 times upper limit of normal (ULN)
AST ≤ 1.5 times ULN
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
Willing to provide blood specimens as required by the study (Mayo Clinic Rochester patients only)
Able to complete questionnaires alone or with assistance
No history of inflammatory bowel disease
No history of gastrointestinal or genitourinary obstruction or porphyria
No history of G6PD deficiency
No history of irritable bowel syndrome
No history of blood dyscrasia
No history of severe allergies or asthma
No history of hepatic or renal disease
No diarrhea ≥ grade 3, rectal bleeding, abdominal cramping, or incontinence of stool within the past week
No medical condition that may interfere with the ability to receive study treatment
No known allergy to sulfasalazine, sulfa medications, salicylates, or any known component of drug formulation

PRIOR CONCURRENT THERAPY:

See Disease Characteristics
No prior pelvic radiotherapy
No prior abdominal-perineal resection, Hartmann procedure, or other surgical procedure leaving the patient without a functioning rectum
No planned use of leucovorin or cytotoxic chemotherapeutic agents concurrent with radiotherapy (except for fluorouracil, capecitabine, or oxaliplatin)
No other concurrent sulfasalazine
No concurrent digoxin

Contacts/Locations Module

Name	Affiliation	Role
Robert C. Miller, MD	Mayo Clinic	Study Chair

Facility	Status	City	State	ZIP	Country	Contacts
Mayo Clinic Hospital		Phoenix	Arizona	85054	United States
Mayo Clinic Scottsdale

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
27354129	Derived	Miller RC, Petereit DG, Sloan JA, Liu H, Martenson JA, Bearden JD 3rd, Sapiente R, Seeger GR, Mowat RB, Liem B, Iott MJ, Loprinzi CL; Alliance for Clinical Trials in Oncology. N08C9 (Alliance): A Phase 3 Randomized Study of Sulfasalazine Versus Placebo in the Prevention of Acute Diarrhea in Patients Receiving Pelvic Radiation Therapy. Int J Radiat Oncol Biol Phys. 2016 Jul 15;95(4):1168-74. doi: 10.1016/j.ijrobp.2016.01.063. Epub 2016 Apr 23.

Label	URL
Data Available: Select individual patient-level data from this trial can be requested from the NCTN/NCORP Data Archive	View source

IPD Sharing Statement Module

No data available

No data is available for this block.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Arm I: Sulfasalazine	Patients receive two 500 mg oral sulfasalazine tablets twice daily during radiotherapy and for 4 weeks after completion of radiotherapy.
FG001	Arm II: Placebo

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

Intervention Browse Module

Masking Info

Patients receive two oral placebo tablets twice daily during radiotherapy and for 4 weeks after completion of radiotherapy.

> placebo: Given orally

Two patients in Arm I and one patient from Arm II were not included in the baseline analysis nor the endpoint analyses due to cancellations and protocol violations.

Arm/Group Information

ID	Title	Description
BG000	Arm I: Sulfasalazine	Patients receive two 500 mg oral sulfasalazine tablets twice daily during radiotherapy and for 4 weeks after completion of radiotherapy.
BG001	Arm II: Placebo	Patients receive two oral placebo tablets twice daily during radiotherapy and for 4 weeks after completion of radiotherapy.> > placebo: Given orally
BG002	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Median

Full Range

years

Title

Denominators

Categories

Title	Measurements
	BG00059(37 to 84) BG00156.5(37 to 81) BG00258(37 to 84)

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG00015 BG00118 BG002

Region of Enrollment

Number

participants

Title

Denominators

Categories

United States

Title	Measurements
	BG00042 BG00142 BG002

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Maximum Severity of Diarrhea Toxicity as Measured by the CTCAE v4.0 During and After Radiotherapy (RT)

The primary endpoint for this study is the maximal severity of diarrhea toxicity. Severity of diarrhea was graded using the terminology and grading categories defined in the NCI's Common Toxicity Criteria (CTCAE), Version 4.0. Grade 0 = None; 1=Mild; Grade 2=Moderate, Grade 3=Severe, Grade 4=Life-threatening as measured by the CTCAE version 4.0. Assessments were recorded during the course of RT and for 6 weeks following RT. The table below represents the worst graded diarrhea for each patient.

A two-sided Wilcoxon rank-sum test will be used to test the equality of the distributions of maximum diarrhea severity grades between the two treatment arms.

Two patients in Arm I and one patient from Arm II were not included in the baseline analysis nor the endpoint analyses due to cancellations and protocol violations.

Posted

Count of Participants

Participants

During radiation therapy and up to 6 weeks post radiation therapy

ID	Title	Description
OG000	Arm I: Sulfasalazine	Patients receive two 500 mg oral sulfasalazine tablets twice daily during radiotherapy and for 4 weeks after completion of radiotherapy.
OG001	Arm II: Placebo	Patients receive two oral placebo tablets twice daily during radiotherapy and for 4 weeks after completion of radiotherapy. > > placebo: Given orally

Units	Counts
Participants	OG00042 OG00142

Title

Denominators

Categories

Grade 0

Title	Measurements
	OG00010 OG00110

Grade 1

Title	Measurements
	OG000

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		Wilcoxon (Mann-Whitney)		0.41														Superiority or Other (legacy)

Secondary

Maximum Severity of Each Outcome Variable (Rectal Bleeding, Abdominal Cramping, Tenesmus, Constipation, and Diarrhea) Measured During and After RT

The maximal severity of each of 5 different adverse even types (Tenesmus, Abdominal Pain, Constipation, Diarrhea, and Rectal Bleeding) were collected as a secondary endpoint. Severity of the events was graded using the terminology and grading categories defined in the NCI's Common Toxicity Criteria (CTCAE), Version 4.0. Grade 0 = None; 1=Mild; Grade 2=Moderate, Grade 3=Severe, Grade 4=Life-threatening. Adverse events were assessed during the course of RT and for 6 weeks following RT. The table below represents the worst grade for each patient for each type.

Two-sided chi-square tests will be used to compare each percentage variable between treatment arms for each event type.

Two patients in Arm I and one patient from Arm II were not included in the endpoint analyses due to cancellations and protocol violations. 42 patients from each arm started RT and were used for the analysis. 25 patients from Arm I and 29 patients from Arm II were evaluated after RT. Two patients from Arm 1 provided incomplete data.

Posted

Count of Participants

Participants

During radiation therapy and up to 6 weeks post radiation therapy

ID	Title	Description
OG000	Arm I: Sulfasalazine	Patients receive two 500 mg oral sulfasalazine tablets twice daily during radiotherapy and for 4 weeks after completion of radiotherapy.
OG001	Arm II: Placebo

Secondary

Area Under the Curve That Combines the Individual Severity of Diarrhea Toxicity as Measured by the CTCAE v4.0 During and After RT

For each patient, an Area Under the Curve (AUC) summary statistic will be calculated taking into account the individual severity of diarrhea toxicity over time. Severity of diarrhea was graded using the terminology and grading categories defined in the NCI's Common Toxicity Criteria (CTCAE), Version 4.0. Grade 0 = None; 1=Mild; Grade 2=Moderate, Grade 3=Severe, Grade 4=Life-threatening. The curve was constructed using weekly assessments during and after RT. A separate analysis was done during the course of RT and every week for 6 weeks following RT.

Two patients in Arm I and one patient from Arm II were not included in the endpoint analyses due to cancellations and protocol violations. 42 patients from each arm started RT and were used in that portion of the analysis. 25 patients from Arm I and 29 patients from Arm II were evaluated after RT. Two patients from Arm 1 provided incomplete data.

Posted

Mean

Standard Deviation

grade*week

During radiation therapy and up to 6 weeks post radiation therapy

ID	Title	Description
OG000	Arm I: Sulfasalazine	Patients receive two 500 mg oral sulfasalazine tablets twice daily during radiotherapy and for 4 weeks after completion of radiotherapy.
OG001	Arm II: Placebo	Patients receive two oral placebo tablets twice daily during radiotherapy and for 4 weeks after completion of radiotherapy.

Secondary

Average Graded Severity for Tenesmus, Abdominal Pain, Constipation, Diarrhea and Hemorrhage During and After RT as Graded by CTCAE v4.0

Tenesmus, Abdominal pain, constipation, diarrhea and hemorrhaging were assessed during RT and up to 6 weeks after RT. Severity of these events were graded using the terminology and grading categories defined in the NCI's Common Toxicity Criteria (CTCAE), Version 4.0. Grade 0 = None; 1=Mild; Grade 2=Moderate, Grade 3=Severe, Grade 4=Life-threatening. For each patient, an average score for each outcome variable during and after RT calculated as follows: The sum of all severity scores for that variable divided by the number of severity scores for that variable recorded for the patient during the course of RT and for 6 weeks following RT.

Two patients in Arm I and one patient from Arm II were not included in the endpoint analyses due to cancellations and protocol violations. 42 patients from each arm started RT and were used in that portion of the analysis. 25 patients from Arm I and 29 patients from Arm II were evaluated after RT. Two patients from Arm 1 provided incomplete data.

Posted

Mean

Standard Deviation

Average Grade of Event

During radiation therapy and up to 6 weeks post radiation therapy

ID	Title	Description
OG000	Arm I: Sulfasalazine	Patients receive two 500 mg oral sulfasalazine tablets twice daily during radiotherapy and for 4 weeks after completion of radiotherapy.
OG001	Arm II: Placebo

Secondary

Percentage of Patients in Each Arm That Experience Tenesmus, Abdominal Pain, Constipation, Diarrhea and Rectal Bleeding During and After RT

The number of patients that reported any grade 1 or higher adverse event was divided by the total number of patients evaluated. The analysis was done separately for each of the 5 outcomes and separately during RT and after RT.

Two patients in Arm I and one patient from Arm II were not included in the endpoint analyses due to cancellations and protocol violations. 42 patients from each arm started RT and were used in that portion of the analysis. 25 patients from Arm I and 29 patients from Arm II were evaluated after RT. Two patients from Arm 1 provided incomplete data.

Posted

Number

percentage of participants

During radiation therapy and up to 6 weeks post radiation therapy

ID	Title	Description
OG000	Arm I: Sulfasalazine	Patients receive two 500 mg oral sulfasalazine tablets twice daily during radiotherapy and for 4 weeks after completion of radiotherapy.
OG001	Arm II: Placebo	Patients receive two oral placebo tablets twice daily during radiotherapy and for 4 weeks after completion of radiotherapy.

Units	Counts

Secondary

Percent of Patients in Each Arm That Recorded "Yes" to Each of Questions 2-10 on the Bowel Function Questionnaire

Questions that were used in this analysis:

2. Have you had a problem causing you to get up at night to have a bowel movement? 3. Have you had a problem causing you to lose control of your bowel movements? 4. Have you had a problem causing you to have a bowel movement within 30 minutes of a prior bowel movement? 5. Have you had to wear protective clothing or a pad in case you lost control of a bowel movement? 6. Have you had a problem causing you to be unable to tell the difference between stool and gas? 7. Have you had a problem causing you to have stools that are liquid? 1=yes 2=no q08 8. Have you found that once you feel the urge to have a bowel movement, you must do so within 15 minutes to avoid an accident? 9. Have you had cramping with a bowel movement? 10. Have you had blood in your bowel movement?

All patients that completed the questionnaire were included in the analysis. Questionnaires used were completed during the last week during RT and 6 weeks after RT.

Posted

Number

percentage of participants

Up to 6 weeks post radiation therapy

ID	Title	Description
OG000	Arm I: Sulfasalazine	Patients receive two 500 mg oral sulfasalazine tablets twice daily during radiotherapy and for 4 weeks after completion of radiotherapy.
OG001	Arm II: Placebo	Patients receive two oral placebo tablets twice daily during radiotherapy and for 4 weeks after completion of radiotherapy.

Secondary

Percentage of Patients in Each Arm That Require Any Type of Antidiarrheal Medications.

The number of patients reporting the use of anti-diarrheal medications divided by the number of patients evaluated for this endpoint.

Two patients in Arm I and one patient from Arm II were not included in the endpoint analyses due to cancellations and protocol violations.

Posted

Number

percentage of participants

Up to 24 months post radiotherapy

ID	Title	Description
OG000	Arm I: Sulfasalazine	Patients receive two 500 mg oral sulfasalazine tablets twice daily during radiotherapy and for 4 weeks after completion of radiotherapy.
OG001	Arm II: Placebo	Patients receive two oral placebo tablets twice daily during radiotherapy and for 4 weeks after completion of radiotherapy.

Units	Counts
Participants	OG000

Secondary

Percentage of Patients in Each Arm That Experience Clinically Significant Deficits in Overall Quality of Life and Fatigue

For each arm, the percentage of patients experience clinically significant deficits in overall QOL and fatigue as indicated by a score of 5 or lower on the 0-10 scale. The analysis was done using the questionnaire that was completed during the first week of radiotherapy (RT) and 6 weeks after RT.

All completed QOL questionnaires were included in the analysis. Questionnaires used were completed during the first week during RT and 6 weeks after RT. From Arm I, 41 patients completed questionnaires, 39 during and 26 after RT. For Arm II, 42 patients completed the questions, 40 during and 29 after RT.

Posted

Number

percentage of participants

Up to 6 weeks post radiotherapy

ID	Title	Description
OG000	Arm I: Sulfasalazine	Patients receive two 500 mg oral sulfasalazine tablets twice daily during radiotherapy and for 4 weeks after completion of radiotherapy.
OG001	Arm II: Placebo	Patients receive two oral placebo tablets twice daily during radiotherapy and for 4 weeks after completion of radiotherapy.

Units	Counts

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Arm I: Sulfasalazine	Patients receive two 500 mg oral sulfasalazine tablets twice daily during radiotherapy and for 4 weeks after completion of radiotherapy.			1	43	42	43
EG001	Arm II: Placebo	placebo: Given orally			2	42	40	42

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anemia	Blood and lymphatic system disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected43 at risk EG0011 events1 affected42 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected43 at risk EG0010 events0 affected42 at risk
Constipation	Gastrointestinal disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected43 at risk EG0011 events1 affected42 at risk
Gastrointestinal disorders - Other, specify	Gastrointestinal disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected43 at risk EG0011 events1 affected42 at risk
Tenesmus	Gastrointestinal disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected43 at risk EG0011 events1 affected42 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anemia	Blood and lymphatic system disorders	MedDRA 12	Systematic Assessment	EG00053 events15 affected43 at risk EG00182 events17 affected42 at risk
Sick sinus syndrome	Cardiac disorders	MedDRA 12	Systematic Assessment	EG0002 events1 affected43 at risk EG0010 events0 affected42 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 12	Systematic Assessment	EG00056 events15 affected43 at risk EG00168 events22 affected42 at risk
Anal pain	Gastrointestinal disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected43 at risk EG0010 events0 affected42 at risk
Constipation	Gastrointestinal disorders	MedDRA 12	Systematic Assessment	EG00040 events15 affected43 at risk EG00157 events15 affected42 at risk
Diarrhea	Gastrointestinal disorders	MedDRA 12	Systematic Assessment	EG000150 events33 affected43 at risk EG001154 events32 affected42 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA 12	Systematic Assessment	EG0002 events1 affected43 at risk EG0011 events1 affected42 at risk
Gastrointestinal disorders - Other, specify	Gastrointestinal disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected43 at risk EG0011 events1 affected42 at risk
Lower gastrointestinal hemorrhage	Gastrointestinal disorders	MedDRA 12	Systematic Assessment	EG00044 events17 affected43 at risk EG00140 events15 affected42 at risk
Mucositis oral	Gastrointestinal disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected43 at risk EG0010 events0 affected42 at risk
Nausea	Gastrointestinal disorders	MedDRA 12	Systematic Assessment	EG0005 events2 affected43 at risk EG0012 events2 affected42 at risk
Rectal pain	Gastrointestinal disorders	MedDRA 12	Systematic Assessment	EG0006 events2 affected43 at risk EG0010 events0 affected42 at risk
Tenesmus	Gastrointestinal disorders	MedDRA 12	Systematic Assessment	EG00043 events17 affected43 at risk EG00149 events16 affected42 at risk
Fatigue	General disorders	MedDRA 12	Systematic Assessment	EG0009 events3 affected43 at risk EG0016 events2 affected42 at risk
Allergic reaction	Immune system disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected43 at risk EG0011 events1 affected42 at risk
Abdominal infection	Infections and infestations	MedDRA 12	Systematic Assessment	EG0001 events1 affected43 at risk EG0010 events0 affected42 at risk
Rash pustular	Infections and infestations	MedDRA 12	Systematic Assessment	EG0002 events1 affected43 at risk EG0010 events0 affected42 at risk
Vaginal infection	Infections and infestations	MedDRA 12	Systematic Assessment	EG0001 events1 affected43 at risk EG0012 events1 affected42 at risk
Dermatitis radiation	Injury, poisoning and procedural complications	MedDRA 12	Systematic Assessment	EG0001 events1 affected43 at risk EG0013 events1 affected42 at risk
Lymphocyte count decreased	Investigations	MedDRA 12	Systematic Assessment	EG0002 events2 affected43 at risk EG00133 events7 affected42 at risk
Neutrophil count decreased	Investigations	MedDRA 12	Systematic Assessment	EG0005 events4 affected43 at risk EG00114 events6 affected42 at risk
Platelet count decreased	Investigations	MedDRA 12	Systematic Assessment	EG00011 events4 affected43 at risk EG00115 events8 affected42 at risk
White blood cell decreased	Investigations	MedDRA 12	Systematic Assessment	EG00022 events8 affected43 at risk EG00157 events18 affected42 at risk
Hypocalcemia	Metabolism and nutrition disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected43 at risk EG0011 events1 affected42 at risk
Hypokalemia	Metabolism and nutrition disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected43 at risk EG0012 events1 affected42 at risk
Hyponatremia	Metabolism and nutrition disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected43 at risk EG0011 events1 affected42 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected43 at risk EG0015 events1 affected42 at risk
Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 12	Systematic Assessment	EG0000 events0 affected43 at risk EG0011 events1 affected42 at risk
Dizziness	Nervous system disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected43 at risk EG0011 events1 affected42 at risk
Headache	Nervous system disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected43 at risk EG0010 events0 affected42 at risk
Peripheral sensory neuropathy	Nervous system disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected43 at risk EG0015 events1 affected42 at risk
Syncope	Nervous system disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected43 at risk EG0010 events0 affected42 at risk
Cystitis noninfective	Renal and urinary disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected43 at risk EG0010 events0 affected42 at risk
Hematuria	Renal and urinary disorders	MedDRA 12	Systematic Assessment	EG0002 events1 affected43 at risk EG0010 events0 affected42 at risk
Urinary frequency	Renal and urinary disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected43 at risk EG0010 events0 affected42 at risk
Palmar-plantar erythrodysesthesia syndrome	Skin and subcutaneous tissue disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected43 at risk EG0011 events1 affected42 at risk
Rash acneiform	Skin and subcutaneous tissue disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected43 at risk EG0011 events1 affected42 at risk
Rash maculo-papular	Skin and subcutaneous tissue disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected43 at risk EG0012 events2 affected42 at risk
Urticaria	Skin and subcutaneous tissue disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected43 at risk EG0011 events1 affected42 at risk

ID	Term
D003967	Diarrhea

ID	Term
D012460	Sulfasalazine

Patients receive two oral placebo tablets twice daily during radiotherapy and for 4 weeks after completion of radiotherapy.

ID	Term
D012817	Signs and Symptoms, Digestive
D012816	Signs and Symptoms
D013568	Pathological Conditions, Signs and Symptoms

ID	Term
D013449	Sulfonamides
D000577	Amides
D009930	Organic Chemicals
D013450	Sulfones
D013457	Sulfur Compounds