Erlotinib in Women With Previously Untreated Adenocarcinoma of the Lung

• Sponsor: Pasi A. Janne, MD, PhD (Other)
• Overall Status: Completed
• CT.gov ID: NCT00137839
• Collaborator: Dana-Farber Cancer Institute (Other), Massachusetts General Hospital (Other), Brigham and Women's Hospital (Other), Beth Israel Deaconess Medical Center (Other), Genentech, Inc. (Industry)
• Enrollment: 84
• Locations: 3
• Arm: 1
• Actual Duration (Months): 175.9
• Patients Per Site: 28
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The purpose of this trial is to figure out what effects (good or bad) the investigational drug agent called Tarceva (erlotinib; OSI-774) has on women with previously untreated adenocarcinoma.

Condition or Disease	Intervention/Treatment	Phase
Adenocarcinoma; Non-small Cell Lung Cancer	Drug: Erlotinib	Phase 2

Detailed Description

Patients will start taking Tarceva daily by mouth on Day 1 and will continue taking this medication daily at home, until participation in the study ends.

Study Design

• Study Type: Interventional
• Actual Enrollment: 84 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Study of Erlotinib (OSI-774); Tarceva in Women With Previously Untreated Advance Adenocarcinoma of the Lung
• Actual Study Start Date: Nov 1, 2004
• Actual Primary Completion Date: Nov 1, 2008
• Actual Study Completion Date: Jul 1, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Erlotinib Erlotinib: 150 mg orally once daily without interruption Cycle duration considered 4 weeks and treatment duration indefinite until disease progression, unacceptable toxicity or withdrawal for other reasons.	Drug: Erlotinib; Other Names: Tarceva OSI-774

Outcome Measures

Primary Outcome Measures

1. Overall Response Rate (ORR) [In this study cohort, treatment duration which parallels the maximum observation time was up to 39 months.]

   ORR is defined as the percentage of participants who achieve partial response (PR) or better on treatment based on RECIST 1.0 criteria: For target lesions, complete response (CR) is disappearance of all target lesions and PR is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD (both require a minimum of 4 weeks). Progressive disease (PD) is at least a 20% increase in sum LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started, or appearance of one or more new target lesions. Stable disease (SD) is neither PR nor PD. For non-target lesions, PD is the appearance of one or more new non-target lesions and/or unequivocal progression of existing non-target lesions.

Secondary Outcome Measures

1. Overall Response Rate (ORR) by EGFR Mutation Status [In this study cohort, treatment duration which parallels the maximum observation time was up to 39 months.]

   ORR is defined as the percentage of participants who achieve partial response (PR) or better on treatment based on RECIST 1.0 criteria: For target lesions, complete response (CR) is disappearance of all target lesions and PR is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD (both require a minimum of 4 weeks). Progressive disease (PD) is at least a 20% increase in sum LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started, or appearance of one or more new target lesions. SD is neither PR nor PD. For non-target lesions, PD is the appearance of one or more new non-target lesions and/or unequivocal progression of existing non-target lesions.

2. Overall Survival (OS) [In this study cohort, participants were followed for survival up to 155 months.]

   OS is defined as the time from study entry to death or date last known alive.

3. Overall Survival by EGFR Mutation Status [In this study cohort, participants were followed for survival up to 155 months.]

   OS is defined as the time from study entry to death or date last known alive.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Female

• Diagnosis of adenocarcinoma of the lung

• Patient has had at least one core biopsy of her tumor

• Must be willing to undergo epidermal growth factor receptor (EGFR) mutation testing of her tumor

• Stage four (IV) or three (III) B non-small cell lung cancer

• Non-smoker or former smoker. Non-smoker is defined as a person who smoked 100 or less cigarettes in her lifetime while a former smoker is defined as a person who has quit smoking one or more years ago.

• Three or more weeks since last radiation therapy

• Three or more weeks since last major surgery

• Must at least be able to walk and capable of taking care of herself although unable to carry out work activities

• Life expectancy of 8 weeks or more

• Blood tests that show kidneys, liver and bone marrow to be working adequately

• Women of child-bearing potential must agree to use adequate contraception prior to study entry and for the entire time enrolled in study

Exclusion Criteria:

• Prior exposure to Tarceva (OSI-774, erlotinib)

• Uncontrolled central nervous system problems

• Prior chemotherapy regimen

• Difficulty swallowing

• A disease or disorder that interferes with ability to digest and absorb food

• Incomplete healing of previous oncologic or other major surgery

• Significant medical history or unstable medical condition such as heart failure, active infection, uncontrolled high blood pressure

• Pregnant or breast feeding

• A medical condition that could make it unsafe for patient to participate in this study

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
2	Beth Israel Deaconess Medical Center	Boston	Massachusetts	United States	02115
3	Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02115

Sponsors and Collaborators

• Pasi A. Janne, MD, PhD
• Dana-Farber Cancer Institute
• Massachusetts General Hospital
• Brigham and Women's Hospital
• Beth Israel Deaconess Medical Center
• Genentech, Inc.

Investigators

• Principal Investigator: Pasi A Janne, MD, PhD, Dana-Farber Cancer Institute

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Dana-Farber Cancer Institute Lowe Thoracic Oncology Program

Publications

• Jänne PA, Engelman JA, Johnson BE. Epidermal growth factor receptor mutations in non-small-cell lung cancer: implications for treatment and tumor biology. J Clin Oncol. 2005 May 10;23(14):3227-34. Review.
• Paez JG, Jänne PA, Lee JC, Tracy S, Greulich H, Gabriel S, Herman P, Kaye FJ, Lindeman N, Boggon TJ, Naoki K, Sasaki H, Fujii Y, Eck MJ, Sellers WR, Johnson BE, Meyerson M. EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science. 2004 Jun 4;304(5676):1497-500. Epub 2004 Apr 29.
• Pérez-Soler R, Chachoua A, Hammond LA, Rowinsky EK, Huberman M, Karp D, Rigas J, Clark GM, Santabárbara P, Bonomi P. Determinants of tumor response and survival with erlotinib in patients with non--small-cell lung cancer. J Clin Oncol. 2004 Aug 15;22(16):3238-47.
• Shepherd FA, Rodrigues Pereira J, Ciuleanu T, Tan EH, Hirsh V, Thongprasert S, Campos D, Maoleekoonpiroj S, Smylie M, Martins R, van Kooten M, Dediu M, Findlay B, Tu D, Johnston D, Bezjak A, Clark G, Santabárbara P, Seymour L; National Cancer Institute of Canada Clinical Trials Group. Erlotinib in previously treated non-small-cell lung cancer. N Engl J Med. 2005 Jul 14;353(2):123-32.

• Responsible Party: Pasi A. Janne, MD, PhD, Associate Professor, Medicine, Dana-Farber Cancer Institute
• ClinicalTrials.gov Identifier: NCT00137839
• Other Study ID Numbers: 04-253
• First Posted: Aug 30, 2005
• Last Update Posted: Dec 17, 2019
• Last Verified: Dec 1, 2019

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Pasi A. Janne, MD, PhD, Associate Professor, Medicine, Dana-Farber Cancer Institute: Tarceva; Erlotinib; OSI-774; Adenocarcinoma; Advanced Lung Cancer
• Additional relevant MeSH terms: Adenocarcinoma; Adenocarcinoma of Lung; Erlotinib Hydrochloride

Study Results

Participant Flow

Recruitment Details	Participants were enrolled November 2004 to November 2008.

Arm/Group Title	Erlotinib
Arm/Group Description	Erlotinib: 150 mg orally once daily without interruption Cycle duration considered 4 weeks and treatment duration indefinite until disease progression, unacceptable toxicity or withdrawal for other reasons.
Period Title: Overall Study
STARTED	84
Treated	83
COMPLETED	0
NOT COMPLETED	84

Baseline Characteristics

Arm/Group Title	Erlotinib
Arm/Group Description	Erlotinib: 150 mg orally once daily without interruption Cycle duration considered 4 weeks and treatment duration indefinite until disease progression, unacceptable toxicity or withdrawal for other reasons.
Overall Participants	84
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	65
Sex: Female, Male (Count of Participants)
Female	84 100%
Male	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	4 4.8%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	2 2.4%
White	78 92.9%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	84 100%
EGFR Status (Count of Participants)
Wild Type	36 42.9%
Mutant	39 46.4%
Unevaluable	9 10.7%

Outcome Measures

1. Primary Outcome

Title	Overall Response Rate (ORR)
Description	ORR is defined as the percentage of participants who achieve partial response (PR) or better on treatment based on RECIST 1.0 criteria: For target lesions, complete response (CR) is disappearance of all target lesions and PR is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD (both require a minimum of 4 weeks). Progressive disease (PD) is at least a 20% increase in sum LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started, or appearance of one or more new target lesions. Stable disease (SD) is neither PR nor PD. For non-target lesions, PD is the appearance of one or more new non-target lesions and/or unequivocal progression of existing non-target lesions.
Time Frame	In this study cohort, treatment duration which parallels the maximum observation time was up to 39 months.

Outcome Measure Data

Analysis Population Description

The analysis dataset is comprised of all treated participants.

Arm/Group Title	Erlotinib
Arm/Group Description	Erlotinib: 150 mg orally once daily without interruption Cycle duration considered 4 weeks and treatment duration indefinite until disease progression, unacceptable toxicity or withdrawal for other reasons.
Measure Participants	83
Number (95% Confidence Interval) [percentage of participants]	27.7 33%

2. Secondary Outcome

Title	Overall Response Rate (ORR) by EGFR Mutation Status
Description	ORR is defined as the percentage of participants who achieve partial response (PR) or better on treatment based on RECIST 1.0 criteria: For target lesions, complete response (CR) is disappearance of all target lesions and PR is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD (both require a minimum of 4 weeks). Progressive disease (PD) is at least a 20% increase in sum LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started, or appearance of one or more new target lesions. SD is neither PR nor PD. For non-target lesions, PD is the appearance of one or more new non-target lesions and/or unequivocal progression of existing non-target lesions.
Time Frame	In this study cohort, treatment duration which parallels the maximum observation time was up to 39 months.

Outcome Measure Data

Analysis Population Description

The analysis dataset is comprised of all treated participants.

Arm/Group Title	EGFR Mutant	EGFR Wild Type	Unevaluable EGFR
Arm/Group Description	Mutation status of the epidermal growth factor receptor (EGFR) gene in tumor specimens was determined by standard methods of immunohistochemistry.	Mutation status in the epidermal growth factor receptor (EGFR) gene in tumor specimens was determined by standard methods of immunohistochemistry.	Mutation status in the epidermal growth factor receptor (EGFR) gene in tumor specimens was determined by standard methods of immunohistochemistry.
Measure Participants	39	35	9
Number (95% Confidence Interval) [percentage of participants]	56.4 67.1%	2.9 NaN	0.0 NaN

3. Secondary Outcome

Title	Overall Survival (OS)
Description	OS is defined as the time from study entry to death or date last known alive.
Time Frame	In this study cohort, participants were followed for survival up to 155 months.

Outcome Measure Data

Analysis Population Description

The analysis dataset is comprised of all enrolled participants.

Arm/Group Title	Erlotinib
Arm/Group Description	Erlotinib: 150 mg orally once daily without interruption Cycle duration considered 4 weeks and treatment duration indefinite until disease progression, unacceptable toxicity or withdrawal for other reasons.
Measure Participants	84
Median (95% Confidence Interval) [months]	22.9

4. Secondary Outcome

Title	Overall Survival by EGFR Mutation Status
Description	OS is defined as the time from study entry to death or date last known alive.
Time Frame	In this study cohort, participants were followed for survival up to 155 months.

Outcome Measure Data

Analysis Population Description

The analysis dataset is comprised of all treated participants.

Arm/Group Title	EGFR Mutant	EGFR Wild Type	Unevaluable EGFR
Arm/Group Description	Mutation status of the epidermal growth factor receptor (EGFR) gene in tumor specimens was determined by standard methods of immunohistochemistry.	Mutation status in the epidermal growth factor receptor (EGFR) gene in tumor specimens was determined by standard methods of immunohistochemistry.	Mutation status in the epidermal growth factor receptor (EGFR) gene in tumor specimens was determined by standard methods of immunohistochemistry.
Measure Participants	39	36	9
Median (95% Confidence Interval) [months]	32.6	9.9	15.7

Adverse Events

Time Frame	Adverse events (AEs) based on the National Cancer Institute's Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3) were assessed every 4 weeks on treatment. In this study cohort, treatment duration which parallels the maximum observation time was up to 39 months.
Adverse Event Reporting Description	Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv3. All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.The analysis dataset for AEs is comprised of all treated participants versus all enrolled for all cause mortality/any death on study.
Arm/Group Title	Erlotinib
Arm/Group Description	Erlotinib: 150 mg orally once daily without interruption Cycle duration considered 4 weeks and treatment duration indefinite until disease progression, unacceptable toxicity or withdrawal for other reasons.
All Cause Mortality
	Erlotinib
	Affected / at Risk (%)	# Events
Total	83/84 (98.8%)
Serious Adverse Events
	Erlotinib
	Affected / at Risk (%)	# Events
Total	33/83 (39.8%)
Gastrointestinal disorders
Diarrhea w/o prior colostomy	5/83 (6%)
Hemorrhoids	5/83 (6%)
Muco/stomatitis by exam, oral cavity	5/83 (6%)
Muco/stomatitis (symptom) oral cavity	5/83 (6%)
Nausea	5/83 (6%)
General disorders
Fatigue	4/83 (4.8%)
Extremity-lower (gait/walking)	4/83 (4.8%)
Hepatobiliary disorders
Liver dysfunction/failure	4/83 (4.8%)
Infections and infestations
Infection Gr0-2 neut, eye NOS	4/83 (4.8%)
Infection Gr0-2 neut, oral cavity	4/83 (4.8%)
Infection Gr0-2 neut, skin	4/83 (4.8%)
Investigations
INR	3/83 (3.6%)
PTT	3/83 (3.6%)
ALT, SGPT	4/83 (4.8%)
AST, SGOT	4/83 (4.8%)
Bilirubin	4/83 (4.8%)
Creatinine	5/83 (6%)
Metabolism and nutrition disorders
Anorexia	5/83 (6%)
Dehydration	5/83 (6%)
Hypoalbuminemia	4/83 (4.8%)
Hypoglycemia	5/83 (6%)
Hyperkalemia	5/83 (6%)
Hyponatremia	4/83 (4.8%)
Respiratory, thoracic and mediastinal disorders
Muco/stomatitis (symptom) pharynx	5/83 (6%)
Skin and subcutaneous tissue disorders
Dry skin	3/83 (3.6%)
Rash/desquamation	5/83 (6%)
Rash: acne/acneiform	14/83 (16.9%)
Skin-other	5/83 (6%)
Vascular disorders
Thrombosis/thrombus/embolism	4/83 (4.8%)
Other (Not Including Serious) Adverse Events
	Erlotinib
	Affected / at Risk (%)	# Events
Total	83/83 (100%)
Blood and lymphatic system disorders
Hemoglobin	12/83 (14.5%)
Hematologic-other	5/83 (6%)
DIC	4/83 (4.8%)
Cardiac disorders
Palpitations	3/83 (3.6%)
Atrial fibrillation	5/83 (6%)
Sinus tachycardia	5/83 (6%)
Arrhythmia-other	5/83 (6%)
C-P arrest, non-fatal, cause unknown	1/83 (1.2%)
Left ventricular systolic dysfunction	5/83 (6%)
Valvular heart disease	5/83 (6%)
Cardiac-other	7/83 (8.4%)
Ear and labyrinth disorders
External ear, pain	4/83 (4.8%)
Endocrine disorders
Hyopthyroidism	5/83 (6%)
Eye disorders
Dry eye syndrome	15/83 (18.1%)
Ocular surface disease	3/83 (3.6%)
Vision-blurred	4/83 (4.8%)
Tearing	3/83 (3.6%)
Ocular-other	4/83 (4.8%)
Eye, pain	4/83 (4.8%)
Gastrointestinal disorders
Constipation	11/83 (13.3%)
Dentures or dental prosthesis	3/83 (3.6%)
Diarrhea w/o prior colostomy	62/83 (74.7%)
Dry mouth	8/83 (9.6%)
Dysphagia	7/83 (8.4%)
Flatulence	2/83 (2.4%)
Gastritis	5/83 (6%)
Dyspepsia	10/83 (12%)
Hemorrhoids	5/83 (6%)
Muco/stomatitis by exam, oral cavity	13/83 (15.7%)
Muco/stomatitis (symptom) oral cavity	5/83 (6%)
Nausea	26/83 (31.3%)
Proctitis	5/83 (6%)
Vomiting	13/83 (15.7%)
GI-other	5/83 (6%)
Anus, hemorrhage	5/83 (6%)
Lower GI, hemorrhage NOS	5/83 (6%)
Rectum, hemorrhage	5/83 (6%)
Upper GI, hemorrhage NOS	5/83 (6%)
Pancreatitis	5/83 (6%)
Abdomen, pain	6/83 (7.2%)
Oral cavity, pain	4/83 (4.8%)
Oral gums, pain	4/83 (4.8%)
General disorders
Fatigue	33/83 (39.8%)
Fever w/o neutropenia	5/83 (6%)
Rigors/chills	3/83 (3.6%)
Constitutional, other	5/83 (6%)
Death - multiorgan failure	1/83 (1.2%)
Death - sudden death	1/83 (1.2%)
Edema limb	6/83 (7.2%)
Extremity-lower (gait/walking)	4/83 (4.8%)
Chest/thoracic pain NOS	12/83 (14.5%)
Pain NOS	4/83 (4.8%)
Pain-other	6/83 (7.2%)
Hepatobiliary disorders
Liver dysfunction/failure	4/83 (4.8%)
Immune system disorders
Allergic reaction	5/83 (6%)
Infections and infestations
Infection w/ gr3-4 neut, wound	4/83 (4.8%)
Infection Gr0-2 neut, external ear	4/83 (4.8%)
Infection Gr0-2 neut, eye NOS	4/83 (4.8%)
Infection Gr0-2 neut, lip/perioral	4/83 (4.8%)
Infection Gr0-2 neut, lung	4/83 (4.8%)
Infection Gr0-2 neut, nerve-periph	4/83 (4.8%)
Infection Gr0-2 neut, oral cavity	4/83 (4.8%)
Infection Gr0-2 neut, skin	6/83 (7.2%)
Infection Gr0-2 neut, stomach	4/83 (4.8%)
Infection Gr0-2 neut, ungual	4/83 (4.8%)
Infection Gr0-2 neut, upper airway	7/83 (8.4%)
Infection Gr0-2 neut, urinary tract	4/83 (4.8%)
Infection Gr0-2 neut, vagina	4/83 (4.8%)
Infection Gr0-2 neut, wound	4/83 (4.8%)
Infection w/ unk ANC conjunctiva	4/83 (4.8%)
Infection w/ unk ANC dental-tooth	4/83 (4.8%)
Infection w/ unk ANC lymphatic	4/83 (4.8%)
Infection w/ unk ANC middle ear	4/83 (4.8%)
Infection w/ unk ANC nose	4/83 (4.8%)
Infection w/ unk ANC oral cavity/gums	4/83 (4.8%)
Infection w/ unk ANC pharynx	4/83 (4.8%)
Infection w/ unk ANC skin (cellulitis)	4/83 (4.8%)
Infection w/ unk ANC ungual (nails)	4/83 (4.8%)
Infection w/ unk ANC upper airway NOS	4/83 (4.8%)
Infection w/ unk ANC urinary tract NOS	5/83 (6%)
Infection w/ unk ANC vagina	4/83 (4.8%)
Infection w/ unk ANC wound	4/83 (4.8%)
Infection Gr 0-2 neut, blood	4/83 (4.8%)
Infection-other	6/83 (7.2%)
Injury, poisoning and procedural complications
Bruising	2/83 (2.4%)
Burn	5/83 (6%)
Fracture	5/83 (6%)
Investigations
Death - disease progression NOS	1/83 (1.2%)
Leukocytes	5/83 (6%)
Neutrophils	5/83 (6%)
Platelets	5/83 (6%)
Weight loss	9/83 (10.8%)
INR	3/83 (3.6%)
PTT	3/83 (3.6%)
Coagulation-other	5/83 (6%)
Alkaline phosphatase	8/83 (9.6%)
ALT, SGPT	11/83 (13.3%)
AST, SGOT	12/83 (14.5%)
Bilirubin	19/83 (22.9%)
Creatinine	5/83 (6%)
Metabolic/Laboratory-other	5/83 (6%)
Metabolism and nutrition disorders
Anorexia	23/83 (27.7%)
Dehydration	5/83 (6%)
Hypoalbuminemia	11/83 (13.3%)
Hypercalcemia	5/83 (6%)
Hypocalcemia	8/83 (9.6%)
Hyperglycemia	15/83 (18.1%)
Hypoglycemia	5/83 (6%)
Hypermagnesemia	4/83 (4.8%)
Hypomagnesemia	5/83 (6%)
Hypophosphatemia	5/83 (6%)
Hyperkalemia	5/83 (6%)
Hypokalemia	7/83 (8.4%)
Hyponatremia	12/83 (14.5%)
Hypertriglyceridemia	5/83 (6%)
Musculoskeletal and connective tissue disorders
Arthritis	5/83 (6%)
Nonneuropathic lower extr muscle weak	5/83 (6%)
Nonneuropathic generalized weakness	5/83 (6%)
Musculoskeletal/soft tissue-other	5/83 (6%)
Back, pain	6/83 (7.2%)
Bone, pain	4/83 (4.8%)
Chest wall, pain	4/83 (4.8%)
Extremity-limb, pain	9/83 (10.8%)
Joint, pain	7/83 (8.4%)
Muscle, pain	5/83 (6%)
Neck, pain	4/83 (4.8%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumor pain	4/83 (4.8%)
Nervous system disorders
Taste disturbance	16/83 (19.3%)
Cognitive disturbance	5/83 (6%)
Dizziness	11/83 (13.3%)
Encephalopathy	4/83 (4.8%)
Memory impairment	5/83 (6%)
Neuropathy CN VII face-motor / taste	5/83 (6%)
Neuropathy-sensory	7/83 (8.4%)
Depressed level of consciousness	4/83 (4.8%)
Syncope	3/83 (3.6%)
Tremor	4/83 (4.8%)
Neurologic-other	5/83 (6%)
Ocular-other	11/83 (13.3%)
Head/headache	5/83 (6%)
Psychiatric disorders
Insomnia	9/83 (10.8%)
Confusion	5/83 (6%)
Anxiety	10/83 (12%)
Depression	6/83 (7.2%)
Renal and urinary disorders
Proteinuria	5/83 (6%)
Obstruction-urethra	5/83 (6%)
Renal failure	3/83 (3.6%)
Urinary frequency/urgency	3/83 (3.6%)
Renal/GU-other	5/83 (6%)
Reproductive system and breast disorders
Breast, pain	4/83 (4.8%)
Vaginal dryness	2/83 (2.4%)
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis	4/83 (4.8%)
Muco/stomatitis by exam, pharynx	5/83 (6%)
Muco/stomatitis (symptom) pharynx	5/83 (6%)
Lung, hemorrhage	5/83 (6%)
Nose, hemorrhage	8/83 (9.6%)
Apnea	3/83 (3.6%)
Throat/pharynx/larynx, pain	4/83 (4.8%)
Bronchospasm, wheezing	5/83 (6%)
Cough	28/83 (33.7%)
Dyspnea	19/83 (22.9%)
Hypoxia	6/83 (7.2%)
Nasal cavity/paranasal sinus reaction	5/83 (6%)
Pneumothorax	5/83 (6%)
Voice changes/dysarthria	7/83 (8.4%)
Pulmonary/Upper Respiratory-other	7/83 (8.4%)
Skin and subcutaneous tissue disorders
Sweating	2/83 (2.4%)
Dry skin	47/83 (56.6%)
Alopecia	21/83 (25.3%)
Hyperpigmentation	2/83 (2.4%)
Induration/fibrosis	3/83 (3.6%)
Nail changes	17/83 (20.5%)
Photosensitivity	5/83 (6%)
Pruritus/itching	23/83 (27.7%)
Rash/desquamation	10/83 (12%)
Rash: acne/acneiform	66/83 (79.5%)
Erythema multiforme	4/83 (4.8%)
Hand-foot reaction	5/83 (6%)
Skin breakdown/decubitus ulcer	4/83 (4.8%)
Ulceration	4/83 (4.8%)
Skin-other	36/83 (43.4%)
Vascular disorders
Hypertension	5/83 (6%)
Hypotension	5/83 (6%)
Hot flashes	3/83 (3.6%)
Hematoma	5/83 (6%)
Hemorrhage-other	4/83 (4.8%)
Thrombosis/thrombus/embolism	4/83 (4.8%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT 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.