Letrozole in Breast Cancer Who Have Received 5 Years of Aromatase Inhibitor Therapy

• Sponsor: Canadian Cancer Trials Group (Other)
• Overall Status: Completed
• CT.gov ID: NCT00754845
• Collaborator: Eastern Cooperative Oncology Group (Other), North Central Cancer Treatment Group (Other), Southwest Oncology Group (Other), Alliance for Clinical Trials in Oncology (Other)
• Enrollment: 1,918
• Locations: 43
• Arms: 2
• Actual Duration (Months): 150.1
• Patients Per Site: 44.6
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

RATIONALE: Estrogen can cause the growth of breast cancer cells. Hormone therapy using letrozole may fight breast cancer by lowering the amount of estrogen the body makes. It is not yet known whether letrozole is more effective than a placebo in treating in women with breast cancer who have already received 5 years of aromatase inhibitor therapy.

PURPOSE: This randomized phase III trial is studying letrozole to see how well it works compared with a placebo in treating women with primary breast cancer who have received 5 years of aromatase inhibitor therapy.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer	Drug: letrozole; Other: placebo	Phase 3

Detailed Description

OBJECTIVES:

Primary

• To compare the disease-free survival of women with primary breast cancer treated with letrozole vs placebo after completing approximately 5 years (i.e., 4½ - 6 years) of aromatase inhibitor therapy (e.g., letrozole, anastrozole, or exemestane).

Secondary

• To compare the effect of these drugs on overall (all cause specific) mortality of these patients.

• To compare the incidence of contralateral breast cancer in patients treated with these drugs.

• To evaluate the long-term clinical and laboratory safety of aromatase inhibitor therapy, particularly cardiovascular morbidity and mortality (e.g., significant coronary artery disease, including myocardial infarction and angina requiring percutaneous transluminal coronary angioplasty or coronary artery bypass graft, fatal and nonfatal strokes, and all vascular deaths); incidence of all bone fractures (with particular emphasis on hip and wrist fractures as indicators of osteoporosis); changes in bone density; and common toxicities.

• To compare overall quality of life (QOL) and menopausal-specific QOL of patients treated with these drugs.

OUTLINE: This is a multicenter study. Patients are stratified according to lymph node status at diagnosis (negative vs positive vs unknown), prior adjuvant chemotherapy (yes vs no), interval between last dose of aromatase inhibitor therapy and study randomization (< 6 months vs 6 months to 2 years), and duration of prior tamoxifen citrate use (0 vs < 2 years vs 2 - 4½ years vs > 4½ years). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive oral letrozole once daily for up to 5 years in the absence of unacceptable toxicity, disease recurrence, or development of a second malignancy.

• Arm II: Patients receive oral placebo once daily for up to 5 years in the absence of unacceptable toxicity, disease recurrence, or development of a second malignancy.

Patients undergo bone mineral density measurement by DEXA scan at baseline (if not done within 12 months of study entry), at 24 and 48 months during study therapy, and at the completion of study therapy. Some patients also complete quality-of-life questionnaires at baseline and at 12, 24, 36, 48, and 60 months.

After completion of study therapy, patients are followed annually.

Study Design

• Study Type: Interventional
• Actual Enrollment: 1918 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Double Blind Randomization to Letrozole or Placebo for Women Previously Diagnosed With Primary Breast Cancer Completing Five Years of Adjuvant Aromatase Inhibitor Either as Initial Therapy or After Tamoxifen (Including Those in The MA.17 Study)
• Actual Study Start Date: Oct 14, 2004
• Actual Primary Completion Date: Dec 21, 2015
• Actual Study Completion Date: Apr 19, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Letrozole Patients receive oral letrozole once daily for up to 5 years in the absence of unacceptable toxicity, disease recurrence, or development of a second malignancy.	Drug: letrozole; Given orally; Other Names: femara
Placebo Comparator: Placebo Patients receive oral placebo once daily for up to 5 years in the absence of unacceptable toxicity, disease recurrence, or development of a second malignancy.	Other: placebo; Given orally; Other Names: sugar pill

Outcome Measures

Primary Outcome Measures

1. Disease-free Survival (DFS) [Unitil the end of study with a median follow up of 75 months]

   It is defined as the months from the day of randomization to the earliest date when a recurrence of the primary disease (recurrence in the breast, chest wall and nodal sites or the development of metastatic disease) or a contralateral breast cancer was observed. Subjects who died without recurrence of the primary disease or the development of the contralateral breast cancer were censored at their death date. If a patient has not recurred, developed a contralateral breast cancer, or died, disease-free survival was censored on the date of the last day the patient was known to be alive. Probability of disease free survival at 5 years is estimated and reported.

Secondary Outcome Measures

1. Incidence of Contralateral Breast Cancer [10 years]

   The annual incidence rate was estimated based on the time to the development of contralateral breast cancer, which was calculated in months from the day of randomization to the diagnosis date of contralateral breast cancer for subjects who had developed the contralateral breast cancer, to the time of death for the patient who died, or to the last day the patient was known alive for subjects without contralateral breast cancer

2. Overall Survival (OS) [Until the end of study with a median follow-up of 75 months]

   For subjects who died, overall survival was calculated in months from the day of randomization to the date of death. Otherwise, survival was censored at the last day the patient was known to be alive. Probability of overall survival at 5 years is estimated and reported.

3. Change From Baseline in Role Function- Physical Scale on SF(Short Form)-36 Health Survey [8 years]

   Difference between post baseline scores and baseline score of role function-physical scale on SF-36 Health Survey (scale range between 0 and 100 with higher score indicating better quality of life).

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A to 120 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

DISEASE CHARACTERISTICS:

• Previously diagnosed with primary breast cancer

• Must have received 4½ - 6 years of aromatase inhibitor therapy (e.g., letrozole, anastrozole, or exemestane), either as initial therapy or after prior tamoxifen citrate, including treatment received as part of clinical trial CAN-NCIC-MA17

• Completed aromatase inhibitor therapy ≤ 2 years ago

• No metastatic or recurrent disease, contralateral breast cancer, or ductal carcinoma in situ in either breast, as determined by the following:

• Clinical examination of the breast area, axillae, and neck within the past 60 days

• Mammogram within the past 12 months*

• Chest x-ray within the past 60 days

• Bone scan, if alkaline phosphatase > 2 times normal and/or there are symptoms of metastatic disease AND confirmatory x-ray, if bone scan results are questionable, within the past 60 days

• Abdominal ultrasound, liver scan, or CT scan of the abdomen within the past 60 days, if ALT, AST, or alkaline phosphatase > 2 times normal NOTE: *A baseline mammogram is not required for patients who have undergone bilateral complete mastectomy

• Hormone-receptor status:

• Estrogen receptor positive (ER+) and/or progesterone receptor positive (PR+) primary tumor at the time of diagnosis, defined as a tumor receptor content of > 10 fmol/mg protein or receptor positive by immunocytochemical assay (for patients not previously enrolled on clinical trial CAN-NCIC-MA17)

• ER+ and/or PR+ primary tumor OR hormone receptor status of primary tumor unknown (for patients previously enrolled on clinical trial CAN-NCIC-MA17)

PATIENT CHARACTERISTICS:

• Menopausal status not specified

• ECOG performance status 0-2

• Life expectancy ≥ 5 years

• WBC > 3.0 x 10^{9/L OR granulocyte count (polymorphs + bands) ≥ 1.5 times 10}9/L

• Platelet count > 100 x 10^9/L

• AST and/or ALT < 2 times upper limit of normal (ULN)*

• Alkaline phosphatase < 2 times ULN*

• Able (i.e. sufficiently fluent) and willing to complete quality-of-life questionnaires in either English or French (NCIC CTG participating centers)

• Inability to complete questionnaires due to illiteracy in English or French, loss of sight, or other equivalent reason allowed

• Accessible for treatment and follow-up

• No other prior or concurrent malignancy except adequately treated, superficial squamous cell or basal cell skin cancer, carcinoma in situ of the cervix, or other cancer treated > 5 years ago that is presumed cured NOTE: *Elevated levels allowed provided imaging examinations have ruled out metastatic disease

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics

• No concurrent selective estrogen receptor modulator (e.g., raloxifene, idoxifene)

• No other concurrent anticancer therapy

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	BCCA - Cancer Centre for the Southern Interior	Kelowna	British Columbia	Canada	V1Y 5L3
2	BCCA - Fraser Valley Cancer Centre	Surrey	British Columbia	Canada	V3V 1Z2
3	BCCA - Vancouver Cancer Centre	Vancouver	British Columbia	Canada	V5Z 4E6
4	BCCA - Vancouver Island Cancer Centre	Victoria	British Columbia	Canada	V8R 6V5
5	CancerCare Manitoba	Winnipeg	Manitoba	Canada	R3E 0V9
6	The Moncton Hospital	Moncton	New Brunswick	Canada	E1C 6Z8
7	The Vitalite Health Network - Dr. Leon Richard	Moncton	New Brunswick	Canada	E1C 8X3
8	Atlantic Health Sciences Corporation	Saint John	New Brunswick	Canada	E2L 4L2
9	Dr. H. Bliss Murphy Cancer Centre	St. John's	Newfoundland and Labrador	Canada	AIB 3V6
10	QEII Health Sciences Center	Halifax	Nova Scotia	Canada	B3H 1V7
11	Juravinski Cancer Centre at Hamilton Health Sciences	Hamilton	Ontario	Canada	L8V 5C2
12	Cancer Centre of Southeastern Ontario at Kingston	Kingston	Ontario	Canada	K7L 5P9
13	London Regional Cancer Program	London	Ontario	Canada	N6A 4L6
14	Credit Valley Hospital	Mississauga	Ontario	Canada	L5M 2N1
15	Stronach Regional Health Centre at Southlake	Newmarket	Ontario	Canada	L3Y 2P9
16	Lakeridge Health Oshawa	Oshawa	Ontario	Canada	L1G 2B9
17	Algoma District Cancer Program	Sault Ste. Marie	Ontario	Canada	P6B 0A8
18	Niagara Health System	St. Catharines	Ontario	Canada	L2R 7C6
19	Northeast Cancer Center Health Sciences	Sudbury	Ontario	Canada	P3E 5J1
20	Thunder Bay Regional Health Science Centre	Thunder Bay	Ontario	Canada	P7B 6V4
21	North York General Hospital	Toronto	Ontario	Canada	M2K 1E1
22	Toronto East General Hospital	Toronto	Ontario	Canada	M4C 3E7
23	Odette Cancer Centre	Toronto	Ontario	Canada	M4N 3M5
24	St. Michael's Hospital	Toronto	Ontario	Canada	M5B 1W8
25	Mount Sinai Hospital	Toronto	Ontario	Canada	M5G 1X5
26	Univ. Health Network-Princess Margaret Hospital	Toronto	Ontario	Canada	M5G 2M9
27	St. Joseph's Health Centre	Toronto	Ontario	Canada	M6R 1B5
28	Trillium Health Centre - West Toronto	Toronto	Ontario	Canada	M9C 1A5
29	Humber River Regional Hospital	Toronto	Ontario	Canada	M9N 1N8
30	Windsor Regional Cancer Centre	Windsor	Ontario	Canada	N8W 2X3
31	PEI Cancer Treatment Centre,Queen Elizabeth Hospital	Charlottetown	Prince Edward Island	Canada	C1A 8T5
32	Centre de Sante et de services sociaux de Gatineau	Gatineau	Quebec	Canada	J8P 7H2
33	Hopital Charles LeMoyne	Greenfield Park	Quebec	Canada	J4V 2H1
34	L'Hotel-Dieu de Levis	Levis	Quebec	Canada	G6V 3Z1
35	Hopital Maisonneuve-Rosemont	Montreal	Quebec	Canada	H1T 2M4
36	McGill University - Dept. Oncology	Montreal	Quebec	Canada	H2W 1S6
37	CHUM - Hotel Dieu du Montreal	Montreal	Quebec	Canada	H2W 1T8
38	Hopital du Sacre-Coeur de Montreal	Montreal	Quebec	Canada	H4J 1C5
39	CHA-Hopital Du St-Sacrement	Quebec City	Quebec	Canada	G1S 4L8
40	Centre hospitalier universitaire de Sherbrooke	Sherbrooke	Quebec	Canada	J1H 5N4
41	Allan Blair Cancer Centre	Regina	Saskatchewan	Canada	S4T 7T1
42	Saskatoon Cancer Centre	Saskatoon	Saskatchewan	Canada	S7N 4H4
43	Wythenshawe Hospital	Manchester		United Kingdom	M23 9LT

Sponsors and Collaborators

• Canadian Cancer Trials Group
• Eastern Cooperative Oncology Group
• North Central Cancer Treatment Group
• Southwest Oncology Group
• Alliance for Clinical Trials in Oncology

Investigators

• Study Chair: Paul E. Goss, MD, PhD, Massachusetts General Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Canadian Cancer Trials Group
• ClinicalTrials.gov Identifier: NCT00754845
• Other Study ID Numbers: MA17R; CAN-NCIC-MA17R; CDR0000614819
• First Posted: Sep 18, 2008
• Last Update Posted: Apr 22, 2020
• Last Verified: Apr 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Keywords provided by Canadian Cancer Trials Group: stage I breast cancer; stage II breast cancer; stage IIIA breast cancer; stage IIIB breast cancer; stage IIIC breast cancer
• Additional relevant MeSH terms: Breast Neoplasms; Letrozole

Study Results

Participant Flow

Arm/Group Title	Letrozole	Placebo
Arm/Group Description	Patients receive oral letrozole once daily for up to 5 years in the absence of unacceptable toxicity, disease recurrence, or development of a second malignancy. letrozole: Given orally	Patients receive oral placebo once daily for up to 5 years in the absence of unacceptable toxicity, disease recurrence, or development of a second malignancy. placebo: Given orally
Period Title: Overall Study
STARTED	959	959
COMPLETED	959	959
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Letrozole	Placebo	Total
Arm/Group Description	Patients receive oral letrozole once daily for up to 5 years in the absence of unacceptable toxicity, disease recurrence, or development of a second malignancy. letrozole: Given orally	Patients receive oral placebo once daily for up to 5 years in the absence of unacceptable toxicity, disease recurrence, or development of a second malignancy. placebo: Given orally	Total of all reporting groups
Overall Participants	959	959	1918
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	65.6	64.8	65.1
Sex: Female, Male (Count of Participants)
Female	959 100%	959 100%	1918 100%
Male	0 0%	0 0%	0 0%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	11 1.1%	13 1.4%	24 1.3%
Not Hispanic or Latino	940 98%	939 97.9%	1879 98%
Unknown or Not Reported	8 0.8%	7 0.7%	15 0.8%
Region of Enrollment (Count of Participants)
Canada	276 28.8%	285 29.7%	561 29.2%
United States	683 71.2%	674 70.3%	1357 70.8%
ECOG Performance Status (Count of Participants)
Grade 0	852 88.8%	856 89.3%	1708 89.1%
Grade 1	100 10.4%	95 9.9%	195 10.2%
Grade 2	7 0.7%	8 0.8%	15 0.8%

Outcome Measures

1. Primary Outcome

Title	Disease-free Survival (DFS)
Description	It is defined as the months from the day of randomization to the earliest date when a recurrence of the primary disease (recurrence in the breast, chest wall and nodal sites or the development of metastatic disease) or a contralateral breast cancer was observed. Subjects who died without recurrence of the primary disease or the development of the contralateral breast cancer were censored at their death date. If a patient has not recurred, developed a contralateral breast cancer, or died, disease-free survival was censored on the date of the last day the patient was known to be alive. Probability of disease free survival at 5 years is estimated and reported.
Time Frame	Unitil the end of study with a median follow up of 75 months

Outcome Measure Data

Analysis Population Description

All women randomized were included in the analysis based on treatment arm they were randomized.

Arm/Group Title	Letrozole	Placebo
Arm/Group Description	Patients receive oral letrozole once daily for up to 5 years in the absence of unacceptable toxicity, disease recurrence, or development of a second malignancy. letrozole: Given orally	Patients receive oral placebo once daily for up to 5 years in the absence of unacceptable toxicity, disease recurrence, or development of a second malignancy. placebo: Given orally
Measure Participants	959	959
Number (95% Confidence Interval) [probability of DFS at 5 years]	0.95	0.91

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Letrozole, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.01
	Comments
	Method	Log Rank
	Comments	Stratified by the stratification factors at randomization
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.66
	Confidence Interval	(2-Sided) 95%; 0.48 to 0.91
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Incidence of Contralateral Breast Cancer
Description	The annual incidence rate was estimated based on the time to the development of contralateral breast cancer, which was calculated in months from the day of randomization to the diagnosis date of contralateral breast cancer for subjects who had developed the contralateral breast cancer, to the time of death for the patient who died, or to the last day the patient was known alive for subjects without contralateral breast cancer
Time Frame	10 years

Outcome Measure Data

Analysis Population Description

All women randomized

Arm/Group Title	Letrozole	Placebo
Arm/Group Description	Patients receive oral letrozole once daily for up to 5 years in the absence of unacceptable toxicity, disease recurrence, or development of a second malignancy. letrozole: Given orally	Patients receive oral placebo once daily for up to 5 years in the absence of unacceptable toxicity, disease recurrence, or development of a second malignancy. placebo: Given orally
Measure Participants	959	959
Number (95% Confidence Interval) [Number of new case per 1000 person years]	2.1	4.9

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Letrozole, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.007
	Comments
	Method	Log Rank
	Comments

3. Secondary Outcome

Title	Overall Survival (OS)
Description	For subjects who died, overall survival was calculated in months from the day of randomization to the date of death. Otherwise, survival was censored at the last day the patient was known to be alive. Probability of overall survival at 5 years is estimated and reported.
Time Frame	Until the end of study with a median follow-up of 75 months

Outcome Measure Data

Analysis Population Description

All women randomized

Arm/Group Title	Arm I	Arm II
Arm/Group Description	Patients receive oral letrozole once daily for up to 5 years in the absence of unacceptable toxicity, disease recurrence, or development of a second malignancy. letrozole: Given orally	Patients receive oral placebo once daily for up to 5 years in the absence of unacceptable toxicity, disease recurrence, or development of a second malignancy. placebo: Given orally
Measure Participants	959	959
Number (95% Confidence Interval) [probability of OS at 5 years]	0.93	0.94

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Letrozole, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.83
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.97
	Confidence Interval	(2-Sided) 95%; 0.73 to 1.28
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Change From Baseline in Role Function- Physical Scale on SF(Short Form)-36 Health Survey
Description	Difference between post baseline scores and baseline score of role function-physical scale on SF-36 Health Survey (scale range between 0 and 100 with higher score indicating better quality of life).
Time Frame	8 years

Outcome Measure Data

Analysis Population Description

All randomized patients.

Arm/Group Title	Letrozole	Placebo
Arm/Group Description	Patients receive oral letrozole once daily for up to 5 years in the absence of unacceptable toxicity, disease recurrence, or development of a second malignancy. letrozole: Given orally	Patients receive oral placebo once daily for up to 5 years in the absence of unacceptable toxicity, disease recurrence, or development of a second malignancy. placebo: Given orally
Measure Participants	959	959
Least Squares Mean (Standard Error) [score on a scale]	-7.74 (1.09)	-6.28 (1.08)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Letrozole, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.01
	Comments
	Method	Mixed Models Analysis
	Comments

Adverse Events

Time Frame	During protocol treatment of 5 years
Arm/Group Title	Arm I		Arm II
Arm/Group Description	Patients receive oral letrozole once daily for up to 5 years in the absence of unacceptable toxicity, disease recurrence, or development of a second malignancy. letrozole: Given orally		Patients receive oral placebo once daily for up to 5 years in the absence of unacceptable toxicity, disease recurrence, or development of a second malignancy. placebo: Given orally
All Cause Mortality
	Arm I		Arm II
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	100/959 (10.4%)		100/954 (10.5%)
Serious Adverse Events
	Arm I		Arm II
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	15/959 (1.6%)		19/954 (2%)
Blood and lymphatic system disorders
CNS hemorrhage/bleeding	0/959 (0%)		1/954 (0.1%)
Melena/GI bleeding	1/959 (0.1%)		0/954 (0%)
Rectal bleeding/ hematochezia	1/959 (0.1%)		0/954 (0%)
Cardiac disorders
Cardiac troponin I (cTnI)	0/959 (0%)		1/954 (0.1%)
Thrombosis/embolism	0/959 (0%)		1/954 (0.1%)
Ventricular arrhythmia (PVCs/bigeminy/trigeminy/ ventricular tachycardia)	1/959 (0.1%)		1/954 (0.1%)
Edema	1/959 (0.1%)		0/954 (0%)
Cardiac left ventricular function	1/959 (0.1%)		1/954 (0.1%)
Cardiac-ischemia/infarction	2/959 (0.2%)		4/954 (0.4%)
Supraventricular arrhythmias (SVT/atrial fibrillation/ flutter)	1/959 (0.1%)		0/954 (0%)
Cardiovascular/ General - Other	1/959 (0.1%)		0/954 (0%)
General disorders
Fatigue	1/959 (0.1%)		0/954 (0%)
Constitutional Symptoms - Other	0/959 (0%)		1/954 (0.1%)
Sudden death	4/959 (0.4%)		1/954 (0.1%)
Hepatobiliary disorders
Liver dysfunction/ failure (clinical)	1/959 (0.1%)		0/954 (0%)
Hepatic - Other	1/959 (0.1%)		0/954 (0%)
Infections and infestations
Infection without neutropenia	2/959 (0.2%)		3/954 (0.3%)
Infection with unknown ANC	0/959 (0%)		1/954 (0.1%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Second malignacy	3/959 (0.3%)		3/954 (0.3%)
Nervous system disorders
CNS cerebrovascular ischemia	0/959 (0%)		3/954 (0.3%)
Neuropathy-motor	0/959 (0%)		1/954 (0.1%)
Renal and urinary disorders
Creatinine	0/959 (0%)		1/954 (0.1%)
Renal failure	3/959 (0.3%)		2/954 (0.2%)
Respiratory, thoracic and mediastinal disorders
Pleural effusion (non-malignant)	0/959 (0%)		1/954 (0.1%)
Hypoxia	1/959 (0.1%)		1/954 (0.1%)
Pulmonary - Other	0/959 (0%)		2/954 (0.2%)
Pneumonitis/pulmonary infiltrates	0/959 (0%)		1/954 (0.1%)
Dyspnea (shortness of breath)	0/959 (0%)		1/954 (0.1%)
Other (Not Including Serious) Adverse Events
	Arm I		Arm II
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	863/959 (90%)		841/954 (88.2%)
Cardiac disorders
Edema	158/959 (16.5%)		136/954 (14.3%)
Hypertension	157/959 (16.4%)		145/954 (15.2%)
Endocrine disorders
Hot flashes/ flushes	360/959 (37.5%)		354/954 (37.1%)
Gastrointestinal disorders
Anorexia	46/959 (4.8%)		52/954 (5.5%)
Constipation	117/959 (12.2%)		140/954 (14.7%)
Diarrhea	105/959 (10.9%)		81/954 (8.5%)
Dyspepsia/heartburn	86/959 (9%)		79/954 (8.3%)
Nausea	69/959 (7.2%)		76/954 (8%)
General disorders
Fatigue	346/959 (36.1%)		355/954 (37.2%)
Sweating	176/959 (18.4%)		175/954 (18.3%)
Abdominal pain	51/959 (5.3%)		38/954 (4%)
Headache	151/959 (15.7%)		138/954 (14.5%)
Arthralgia	513/959 (53.5%)		475/954 (49.8%)
Myalgia	268/959 (27.9%)		240/954 (25.2%)
Bone pain	174/959 (18.1%)		133/954 (13.9%)
Pain-Other	73/959 (7.6%)		77/954 (8.1%)
Infections and infestations
Infection w/o neutropenia	81/959 (8.4%)		82/954 (8.6%)
Metabolism and nutrition disorders
Hypercholesterolemia	203/959 (21.2%)		184/954 (19.3%)
Hyperglycemia	56/959 (5.8%)		66/954 (6.9%)
Musculoskeletal and connective tissue disorders
Arthritis	317/959 (33.1%)		288/954 (30.2%)
Nervous system disorders
Anxiety	54/959 (5.6%)		56/954 (5.9%)
Dizziness	145/959 (15.1%)		139/954 (14.6%)
Insomnia	269/959 (28.1%)		243/954 (25.5%)
Depression	152/959 (15.8%)		150/954 (15.7%)
Neuropathy-sensory	110/959 (11.5%)		107/954 (11.2%)
Reproductive system and breast disorders
Vaginal dryness	102/959 (10.6%)		96/954 (10.1%)
Respiratory, thoracic and mediastinal disorders
Cough	63/959 (6.6%)		69/954 (7.2%)
Dyspnea	148/959 (15.4%)		165/954 (17.3%)
Skin and subcutaneous tissue disorders
Alopecia	61/959 (6.4%)		64/954 (6.7%)

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.