Dexamethasone in Reducing Oral Pain and Dry Mouth After Surgery in Patients With Oropharyngeal Cancer

• Sponsor: OHSU Knight Cancer Institute
• Collaborator: National Cancer Institute (NCI)
• Information provided by (Responsible Party): Daniel Clayburgh, OHSU Knight Cancer Institute

Study Type	Interventional
Study Design	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Supportive Care
Conditions	Dysphagia; Pain; Stage I Oropharyngeal Squamous Cell Carcinoma; Stage II Oropharyngeal Squamous Cell Carcinoma; Stage III Oropharyngeal Squamous Cell Carcinoma
Interventions	Drug: Dexamethasone; Other: Placebo; Procedure: Quality-of-Life Assessment; Other: Questionnaire Administration; Procedure: Transoral Robotic Surgery
Enrollment	76

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	Arm I (Treatment)	Arm II (Control)
Arm/Group Description	Patients receive dexamethasone IV at the time of surgery and PO every 8 hours for up to 4 days following surgery. Dexamethasone: Given IV Dexamethasone: Given PO Quality-of-Life Assessment: Ancillary studies Questionnaire Administration: Ancillary studies Transoral Robotic Surgery: Undergo TORS	Patients receive dexamethasone IV at the time of surgery and placebo PO every 8 hours for up to 4 days following surgery. Dexamethasone: Given IV Placebo: Given PO Quality-of-Life Assessment: Ancillary studies Questionnaire Administration: Ancillary studies Transoral Robotic Surgery: Undergo TORS
Period Title: Overall Study
Started	39	37
Completed	35	33
Not Completed	4	4

Baseline Characteristics

Arm/Group Title		Arm I (Treatment)	Arm II (Control)	Total
Arm/Group Description		Patients receive dexamethasone IV at the time of surgery and PO every 8 hours for up to 4 days following surgery. Dexamethasone: Given IV Dexamethasone: Given PO Quality-of-Life Assessment: Ancillary studies Questionnaire Administration: Ancillary studies Transoral Robotic Surgery: Undergo TORS	Patients receive dexamethasone IV at the time of surgery and placebo PO every 8 hours for up to 4 days following surgery. Dexamethasone: Given IV Placebo: Given PO Quality-of-Life Assessment: Ancillary studies Questionnaire Administration: Ancillary studies Transoral Robotic Surgery: Undergo TORS	Total of all reporting groups
Overall Number of Baseline Participants		35	33	68
Baseline Analysis Population Description		[Not Specified]
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	35 participants	33 participants	68 participants
	<=18 years	0 0.0%	0 0.0%	0 0.0%
	Between 18 and 65 years	32 91.4%	28 84.8%	60 88.2%
	>=65 years	3 8.6%	5 15.2%	8 11.8%
Age, Continuous; Mean (Full Range); Unit of measure: Years
	Number Analyzed	35 participants	33 participants	68 participants
		56; (44 to 72)	60; (44 to 75)	58; (44 to 75)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	35 participants	33 participants	68 participants
	Female	3 8.6%	4 12.1%	7 10.3%
	Male	32 91.4%	29 87.9%	61 89.7%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants
United States	Number Analyzed	35 participants	33 participants	68 participants
		35	33	68
VAS pain score [1]; Mean (Standard Deviation); Unit of measure: Units on a scale
	Number Analyzed	35 participants	33 participants	68 participants
		1.1 (1.8)	0.6 (1.3)	0.9 (1.6)
		[1] Measure Description: Visual Analog Scale (VAS) is a 0-10 scale for patients to indicate intensity level of pain with 0 indicating "No pain" and 10 indicating "Worst possible, unbearable, excruciating pain".
Tumor stage [1]; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	35 participants	33 participants	68 participants
	T1	21 60.0%	15 45.5%	36 52.9%
	T2	14 40.0%	18 54.5%	32 47.1%
		[1] Measure Description: Tumor stage is assessed using American Joint Committee on Cancer (AJCC) TNM staging of oropharyngeal squamous cell carcinoma: T1 = Tumor 2 cm or less in greatest dimension. T2 = Tumor more than 2 cm but not more than 4 cm in greatest dimension. T3 = Tumor more than 4 cm in greatest dimension or extension to lingual surface of epiglottis. T4a = Moderately advanced local disease. T4b = Very advance local disease.
EAT-10 score [1]; Mean (Standard Deviation); Unit of measure: Units on a scale
	Number Analyzed	35 participants	33 participants	68 participants
		5.9 (7.6)	3.5 (6.2)	4.6 (6.9)
		[1] Measure Description: Mean overall score of the EAT-10 tool. The Eating Assessment Tool (EAT-10) is a 10 item questionnaire that evaluates swallowing and the extent of how problematic with certain eating activities. Questions are answered using a five point (0-4) plus Not Applicable scale with 0 = "No problem" and 4= "Severe problem".
PSS normalcy of diet [1]; Mean (Standard Deviation); Unit of measure: Units on a scale
	Number Analyzed	35 participants	33 participants	68 participants
		92.3 (16.4)	94.2 (15.0)	93.8 (15.4)
		[1] Measure Description: Performance Status Score (PSS) - Normalcy of Diet score is a 0-100 scale that measures diet restrictions with 0= "Non-oral feeding (tube fed)" and 100 = "Full diet (no restrictions)"
UM-QOL eating score [1]; Mean (Standard Deviation); Unit of measure: Units on a scale
	Number Analyzed	35 participants	33 participants	68 participants
		89.6 (17.8)	93.75 (12.7)	89.6 (17.8)
		[1] Measure Description: The University of Michigan Head and Neck Quality of Life Questionnaire (UM-QOL) is 20 item, 1-5 scale, questionnaire that measures how much the patient has been bothered during various activities as a result of head and neck condition or treatment in the past four weeks with 1= "Not at all" and 5="Extremely".

Outcome Measures

1. Primary Outcome

Title	Pain Visual Analogue Scale (VAS) Score Measured at 10-point Scale
Description	Visual Analog Scale (VAS) is a 0-10 scale for patients to indicate intensity level of pain with 0 indicating "No pain" and 10 indicating "Worst possible, unbearable, excruciating pain". A descriptive time plot of VAS scores will be produced for all enrolled subjects, with loess curve fitted separately for the experimental and control groups. A linear mixed effects model will be used to compare the pain VAS scores between the experimental and control groups.
Time Frame	21 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm I (Treatment)	Arm II (Control)
Arm/Group Description:	Patients receive dexamethasone IV at the time of surgery and PO every 8 hours for up to 4 days following surgery. Dexamethasone: Given IV Dexamethasone: Given PO Quality-of-Life Assessment: Ancillary studies Questionnaire Administration: Ancillary studies Transoral Robotic Surgery: Undergo TORS	Patients receive dexamethasone IV at the time of surgery and placebo PO every 8 hours for up to 4 days following surgery. Dexamethasone: Given IV Placebo: Given PO Quality-of-Life Assessment: Ancillary studies Questionnaire Administration: Ancillary studies Transoral Robotic Surgery: Undergo TORS
Overall Number of Participants Analyzed	35	33
Mean (Standard Deviation); Unit of Measure: units on a scale
Postoperative day #1	7.4 (2.0)	6.8 (2.3)
Postoperative day #2	6.0 (2.0)	6.4 (2.1)
Postoperative day #3	5.3 (2.0)	6.7 (1.9)
Postoperative day #7-21	3.0 (1.8)	2.5 (1.9)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm I (Treatment), Arm II (Control)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.25
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]

2. Secondary Outcome

Title	Complications Associated With Postoperative Corticosteroid Use After TORS
Description	A descriptive statistical analysis will be conducted on complications.
Time Frame	Up to 30 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm I (Treatment)	Arm II (Control)
Arm/Group Description:	Patients receive dexamethasone IV at the time of surgery and PO every 8 hours for up to 4 days following surgery. Dexamethasone: Given IV Dexamethasone: Given PO Quality-of-Life Assessment: Ancillary studies Questionnaire Administration: Ancillary studies Transoral Robotic Surgery: Undergo TORS	Patients receive dexamethasone IV at the time of surgery and placebo PO every 8 hours for up to 4 days following surgery. Dexamethasone: Given IV Placebo: Given PO Quality-of-Life Assessment: Ancillary studies Questionnaire Administration: Ancillary studies Transoral Robotic Surgery: Undergo TORS
Overall Number of Participants Analyzed	35	33
Measure Type: Count of Participants; Unit of Measure: Participants
complication present	10 28.6%	7 21.2%
no complication	25 71.4%	26 78.8%

3. Secondary Outcome

Title	Eating Assessment Tool (EAT)-10 Scores
Description	Statistical Analysis between placebo and steroid cohorts to assess differences. The Eating Assessment Tool (EAT-10) is a 10 item questionnaire that evaluates swallowing and the extent of how problematic with certain eating activities. Questions are answered using a five point (0-4) plus Not Applicable scale with 0 = "No problem" and 4= "Severe problem". A descriptive time plot will be produced for EAT-10 scores using baseline and postoperative measurements on days 3 and day 7-21. Descriptive statistical analyses will be conducted for a summary of EAT-10 scores at baseline, days 3 and day 7-21 after surgery. A linear mixed effects model will be used to compare the EAT-10 scores between the two groups.
Time Frame	Up to 12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm I (Treatment)	Arm II (Control)
Arm/Group Description:	Patients receive dexamethasone IV at the time of surgery and PO every 8 hours for up to 4 days following surgery. Dexamethasone: Given IV Dexamethasone: Given PO Quality-of-Life Assessment: Ancillary studies Questionnaire Administration: Ancillary studies Transoral Robotic Surgery: Undergo TORS	Patients receive dexamethasone IV at the time of surgery and placebo PO every 8 hours for up to 4 days following surgery. Dexamethasone: Given IV Placebo: Given PO Quality-of-Life Assessment: Ancillary studies Questionnaire Administration: Ancillary studies Transoral Robotic Surgery: Undergo TORS
Overall Number of Participants Analyzed	35	33
Mean (Standard Deviation); Unit of Measure: units on a scale
	20.0 (8.3)	20.2 (10.7)

4. Secondary Outcome

Title	Length of Hospital Stay (Number of Days Between the Date of Surgery and Date of Discharge)
Description	Kaplan-Meier functions will be fitted to compare the length of hospital stay between the experimental and control groups.
Time Frame	Up to 21 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm I (Treatment)	Arm II (Control)
Arm/Group Description:	Patients receive dexamethasone IV at the time of surgery and PO every 8 hours for up to 4 days following surgery. Dexamethasone: Given IV Dexamethasone: Given PO Quality-of-Life Assessment: Ancillary studies Questionnaire Administration: Ancillary studies Transoral Robotic Surgery: Undergo TORS	Patients receive dexamethasone IV at the time of surgery and placebo PO every 8 hours for up to 4 days following surgery. Dexamethasone: Given IV Placebo: Given PO Quality-of-Life Assessment: Ancillary studies Questionnaire Administration: Ancillary studies Transoral Robotic Surgery: Undergo TORS
Overall Number of Participants Analyzed	35	33
Median (Standard Deviation); Unit of Measure: days
	5 (1.9)	4 (1.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm I (Treatment), Arm II (Control)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]

5. Secondary Outcome

Title	PSS Normalcy of Diet
Description	Performance Status Score (PSS) - Normalcy of Diet score is a 0-100 scale that measures diet restrictions with 0= "Non-oral feeding (tube fed)" and 100 = "Full diet (no restrictions)"
Time Frame	30 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm I (Treatment)	Arm II (Control)
Arm/Group Description:	Patients receive dexamethasone IV at the time of surgery and PO every 8 hours for up to 4 days following surgery. Dexamethasone: Given IV Dexamethasone: Given PO Quality-of-Life Assessment: Ancillary studies Questionnaire Administration: Ancillary studies Transoral Robotic Surgery: Undergo TORS	Patients receive dexamethasone IV at the time of surgery and placebo PO every 8 hours for up to 4 days following surgery. Dexamethasone: Given IV Placebo: Given PO Quality-of-Life Assessment: Ancillary studies Questionnaire Administration: Ancillary studies Transoral Robotic Surgery: Undergo TORS
Overall Number of Participants Analyzed	35	33
Mean (Standard Deviation); Unit of Measure: units on a scale
	51.7 (24.4)	36.7 (23.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm I (Treatment), Arm II (Control)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.009
	Comments	[Not Specified]
	Method	Wilcoxon (Mann-Whitney)
	Comments	[Not Specified]

6. Secondary Outcome

Title	Opioid Use
Description	[Not Specified]
Time Frame	3 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm I (Treatment)	Arm II (Control)
Arm/Group Description:	Patients receive dexamethasone IV at the time of surgery and PO every 8 hours for up to 4 days following surgery. Dexamethasone: Given IV Dexamethasone: Given PO Quality-of-Life Assessment: Ancillary studies Questionnaire Administration: Ancillary studies Transoral Robotic Surgery: Undergo TORS	Patients receive dexamethasone IV at the time of surgery and placebo PO every 8 hours for up to 4 days following surgery. Dexamethasone: Given IV Placebo: Given PO Quality-of-Life Assessment: Ancillary studies Questionnaire Administration: Ancillary studies Transoral Robotic Surgery: Undergo TORS
Overall Number of Participants Analyzed	35	33
Mean (Standard Deviation); Unit of Measure: mg of oxycodone equivalent
	137.1 (115.2)	147.3 (90.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm I (Treatment), Arm II (Control)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.33
	Comments	[Not Specified]
	Method	Wilcoxon (Mann-Whitney)
	Comments	[Not Specified]

7. Secondary Outcome

Title	UM-QOL Eating
Description	The University of Michigan Head and Neck Quality of Life Questionnaire (UM-QOL) is 20 item, 1-5 scale, questionnaire that measures how much the patient has been bothered during various activities as a result of head and neck condition or treatment in the past four weeks with 1= "Not at all" and 5="Extremely". The scores are calculated using a Likert Scale, which transforms the 1-5 choices into a 0-100 scale with 100 being normal and 0 being poor quality of life. This test contains separate domains (eating, etc.) that can be scored independently. Scores were analyzed between cohorts pre and post operatively.
Time Frame	21 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm I (Treatment)	Arm II (Control)
Arm/Group Description:	Patients receive dexamethasone IV at the time of surgery and PO every 8 hours for up to 4 days following surgery. Dexamethasone: Given IV Dexamethasone: Given PO Quality-of-Life Assessment: Ancillary studies Questionnaire Administration: Ancillary studies Transoral Robotic Surgery: Undergo TORS	Patients receive dexamethasone IV at the time of surgery and placebo PO every 8 hours for up to 4 days following surgery. Dexamethasone: Given IV Placebo: Given PO Quality-of-Life Assessment: Ancillary studies Questionnaire Administration: Ancillary studies Transoral Robotic Surgery: Undergo TORS
Overall Number of Participants Analyzed	35	33
Mean (Standard Deviation); Unit of Measure: units on a scale
	59.3 (19.5)	60.1 (19.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm I (Treatment), Arm II (Control)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.96
	Comments	[Not Specified]
	Method	Wilcoxon (Mann-Whitney)
	Comments	[Not Specified]

8. Secondary Outcome

Title	Days With Feeding Tube
Description	[Not Specified]
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm I (Treatment)	Arm II (Control)
Arm/Group Description:	Patients receive dexamethasone IV at the time of surgery and PO every 8 hours for up to 4 days following surgery. Dexamethasone: Given IV Dexamethasone: Given PO Quality-of-Life Assessment: Ancillary studies Questionnaire Administration: Ancillary studies Transoral Robotic Surgery: Undergo TORS	Patients receive dexamethasone IV at the time of surgery and placebo PO every 8 hours for up to 4 days following surgery. Dexamethasone: Given IV Placebo: Given PO Quality-of-Life Assessment: Ancillary studies Questionnaire Administration: Ancillary studies Transoral Robotic Surgery: Undergo TORS
Overall Number of Participants Analyzed	35	33
Median (Full Range); Unit of Measure: days
	4; (2 to 311)	11; (2 to 298)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm I (Treatment), Arm II (Control)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.15
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]

Adverse Events

Time Frame	[Not Specified]
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Arm I (Treatment)		Arm II (Control)
Arm/Group Description	Patients receive dexamethasone IV at the time of surgery and PO every 8 hours for up to 4 days following surgery. Dexamethasone: Given IV Dexamethasone: Given PO Quality-of-Life Assessment: Ancillary studies Questionnaire Administration: Ancillary studies Transoral Robotic Surgery: Undergo TORS		Patients receive dexamethasone IV at the time of surgery and placebo PO every 8 hours for up to 4 days following surgery. Dexamethasone: Given IV Placebo: Given PO Quality-of-Life Assessment: Ancillary studies Questionnaire Administration: Ancillary studies Transoral Robotic Surgery: Undergo TORS
All-Cause Mortality
	Arm I (Treatment)		Arm II (Control)
	Affected / at Risk (%)		Affected / at Risk (%)
Total	--/--		--/--
Serious Adverse Events
	Arm I (Treatment)		Arm II (Control)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	10/35 (28.57%)		7/33 (21.21%)
Respiratory, thoracic and mediastinal disorders
Pneumonia	0/35 (0.00%)		3/33 (9.09%)
Surgical and medical procedures
oropharyngeal hemorrhage †	4/35 (11.43%)		3/33 (9.09%)	3
Neck hematoma	2/35 (5.71%)		1/33 (3.03%)
Chyle leak	1/35 (2.86%)		0/33 (0.00%)
Readmission/failure to thrive	2/35 (5.71%)		0/33 (0.00%)
abscess	1/35 (2.86%)		0/33 (0.00%)
† Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Arm I (Treatment)		Arm II (Control)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/35 (0.00%)		0/33 (0.00%)

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

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

Results Point of Contact

Name/Title: Daniel Clayburgh, MD PhD

Organization: Oregon Health and Science University

Phone: 503-494-8510

EMail: clayburg@ohsu.edu

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Clayburgh D, Stott W, Bolognone R, Palmer A, Achim V, Troob S, Li R, Brickman D, Graville D, Andersen P, Gross ND. A randomized controlled trial of corticosteroids for pain after transoral robotic surgery. Laryngoscope. 2017 Nov;127(11):2558-2564. doi: 10.1002/lary.26625. Epub 2017 Aug 29.

Responsible Party:	Daniel Clayburgh, OHSU Knight Cancer Institute
ClinicalTrials.gov Identifier:	NCT01748942 History of Changes
Other Study ID Numbers:	IRB00008071; NCI-2012-02780 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ); CPC-12095-L; CR00021919; IRB00008071 ( Other Identifier: OHSU Knight Cancer Institute ); P30CA069533 ( U.S. NIH Grant/Contract )
First Submitted:	December 11, 2012
First Posted:	December 13, 2012
Results First Submitted:	May 8, 2017
Results First Posted:	September 12, 2017
Last Update Posted:	June 19, 2018