Trastuzumab, Ixabepilone, and Carboplatin in Treating Pat... | NCT00077376

ID	Type	Description	Link
NCI-2012-02946	Registry Identifier	CTRP (Clinical Trial Reporting Program)
U10CA023318	U.S. NIH Grant/Contract		View source
E2103	Other Identifier	Eastern Cooperative Oncology Group
E2103	Other Identifier	CTEP
U10CA021115	U.S. NIH Grant/Contract		View source

Status Module

Description Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Treatment (trastuzumab, ixabepilone, carboplatin)	Experimental	Induction therapy: Patients receive trastuzumab (Herceptin®) IV over 30 minutes* on days 1, 8, 15, and 22 and ixabepilone IV over 1 hour and carboplatin IV over 1 hour on days 1, 8, and 15. Treatment repeats every 28 days for up to 6 courses in the absence of unacceptable toxicity. NOTE: *Trastuzumab is given over 90 minutes on day 1 of course 1 (induction therapy) only. Maintenance therapy: Patients receive trastuzumab IV over 90 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Biological: trastuzumab Drug: ixabepilone Drug: carboplatin Other: laboratory biomarker analysis

Name	Type	Description	Arm Group Labels	Other Names
trastuzumab	Biological	Given IV	Treatment (trastuzumab, ixabepilone, carboplatin)

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Objective Response for HER2+ Patients (Best Objective Response a Patient Has Ever Experienced on Study)	To assess objective response, it is necessary to estimate the overall tumor burden at baseline to which subsequent measurements will be compared. The same method of assessment and the same technique should be used to characterize each lesion at baseline and during follow-up. The best overall response based on RECIST is the best response recorded from registration until disease progression/recurrence, taking as reference for progressive disease the smallest measurements recorded since registration. The best response was determined based on the tumor responses in target and nontarget lesions, with or without new lesions. To be assigned a status of complete or partial response, changes in tumor measurements must be confirmed by repeat assessments performed no less than 4 weeks after the criteria for response are first met. To be assigned a status of stable disease, measurements must have met the stable disease criteria at least once after study entry at a minimum interval of 8 weeks.	Assessed every 3 cycles during induction therapy and every 6 cycles during maintenance therapy until disease progression or up to 5 years

Secondary Outcomes

Measure	Description	Time Frame
Objective Response for All Treated Patients (the Best Response a Patient Has Ever Experienced on Study)	To assess objective response, it is necessary to estimate the overall tumor burden at baseline to which subsequent measurements will be compared. The same method of assessment and the same technique should be used to characterize each lesion at baseline and during follow-up. The best overall response based on RECIST is the best response recorded from registration until disease progression/recurrence, taking as reference for progressive disease the smallest measurements recorded since registration. The best response was determined based on the tumor responses in target and nontarget lesions, with or without new lesions. To be assigned a status of complete or partial response, changes in tumor measurements must be confirmed by repeat assessments performed no less than 4 weeks after the criteria for response are first met. To be assigned a status of stable disease, measurements must have met the stable disease criteria at least once after study entry at a minimum interval of 8 weeks.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Patients with histologically confirmed adenocarcinoma of the breast which is metastatic and is known to overexpress HER2/neu who have received no prior chemotherapy for metastatic breast cancer; prior hormonal therapy for metastatic disease is allowed; NOTE: for this protocol, HER2 overexpression will be defined as 3+ HER2 positivity as measured by immunohistochemistry using the HercepTest (DAKO) or HER2 gene amplification as measured by fluorescent in-situ hybridization (FISH, e.g. Vysis); representative diagnostic tissue must be submitted for central diagnostic review
Patients must not be pregnant or breast feeding because of the teratogenic potential of these drugs; it is recommended that all females of childbearing potential have a blood test or urine study within 2 weeks prior to registration to rule out pregnancy; women of childbearing potential and sexually active males must be strongly advised to use an accepted and effective non-hormonal method of contraception
Patients must have at least one objective measurable disease parameter; baseline measurements and evaluations using RECIST criteria guidelines must be obtained within 4 weeks prior to registration to the study; NOTE: all areas of disease should be recorded and followed
Patients must have an ECOG performance status of 0 or 1
Patients must be disease free of prior malignancy for >= 5 years with the exception of curatively treated basal cell carcinoma or squamous cell carcinomas of the skin or carcinoma in situ of the cervix
Patients must not have a history of untreated brain metastasis or brain metastasis currently undergoing radiation; patients with brain metastasis representing the sole site of disease are not eligible for this study; patients with previously treated brain metastasis who have responded to brain radiotherapy and/or surgery and continue in response are eligible provided the brain is not the only site of measurable disease
Patients must not have peripheral neuropathy of any grade
Patients must not have a history of prior severe (grade 3 or 4) hypersensitivity reaction to a drug formulated in polyoxyethylated castor oil (Cremophor EL)
Patients must have left ventricular ejection fraction by MUGA scan or echocardiogram that is at or above the lower institutional limits of normal obtained within 6 weeks prior to registration
Patients must not have a history of New York Heart Association class 3 or 4 heart failure
Serum creatinine =< 1.5 mg/dl
Granulocytes >= 1500/mm^3
Platelets >= 100,000/mm^3
SGOT(AST) and SGPT(ALT) =< 1.5 x upper limit of normal (unless liver is involved by tumor, in which case SGOT(AST) and SGPT(ALT) can be =< 2.0 x upper limit of normal)
Patients must have no history of prior therapy with trastuzumab (Herceptin), Ixabepilone (BMS-247550) or carboplatin for metastatic disease; patients who develop metastatic disease =< 6 months after completing adjuvant trastuzumab (Herceptin), paclitaxel, docetaxel, carboplatin, or Ixabepilone (BMS-247550) are considered to have had prior therapy for metastatic disease and are excluded from study participation
Patients must not have received a cumulative dose of doxorubicin of greater than 360 mg/m^2 or epirubicin of greater than 640 mg/m^2
Concurrent use of hormonal therapy is not permitted; concurrent radiation therapy is not permitted; hormonal therapy must have been discontinued >= 1 week prior to registration; radiation therapy must have been completed >= 2 weeks prior to registration
Patients may have had prior radiation therapy, but the previously irradiated tumors cannot be used to assess a clinical response; patients will not be eligible if they do not have other areas of measurable disease; an exception will be given for patients who have had tumor recurrence in an area that received adjuvant radiation treatments, such as the axilla or chest wall

Name	Affiliation	Role
Stacy Moulder	Eastern Cooperative Oncology Group	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Eastern Cooperative Oncology Group		Boston	Massachusetts	02215	United States

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Trastuzumab/Ixabepilone/Carboplatin	During the induction phase, patients were treated with Ixabepilone (BMS-247550) 15mg/m2 intravenously (IV) followed by carboplatin (AUC=2 IV) on days 1, 8 and 15 of a 28-day cycle for a maximum of 6 cycles. Trastuzumab was administered weekly (4mg/kg loading dose then 2mg/kg IV) starting on day 1. Routine premedication included H1 blocker (diphenhydramine 50 mg orally (PO) or IV), H2 blocker (ranitidine 150 mg PO or 50 mg IV or another equivalent H2 blocker), and at least a 5-HT3 antagonist and dexamethasone. After completion of 24 weekly trastuzumab doses (induction therapy), trastuzumab were given at a dose of 6 mg/kg IV every 3 weeks (maintenance therapy) beginning one week after the 24th weekly dose. Trastuzumab were repeated every 21 days until disease progression or prohibitive toxicity.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

ID	Title	Description
BG000	Trastuzumab/Ixabepilone/Carboplatin	During the induction phase, patients were treated with Ixabepilone (BMS-247550) 15mg/m2 intravenously (IV) followed by carboplatin (AUC=2 IV) on days 1, 8 and 15 of a 28-day cycle for a maximum of 6 cycles. Trastuzumab was administered weekly (4mg/kg loading dose then 2mg/kg IV) starting on day 1. Routine premedication included H1 blocker (diphenhydramine 50 mg orally (PO) or IV), H2 blocker (ranitidine 150 mg PO or 50 mg IV or another equivalent H2 blocker), and at least a 5-HT3 antagonist and dexamethasone. After completion of 24 weekly trastuzumab doses (induction therapy), trastuzumab were given at a dose of 6 mg/kg IV every 3 weeks (maintenance therapy) beginning one week after the 24th weekly dose. Trastuzumab were repeated every 21 days until disease progression or prohibitive toxicity.

Units	Counts
Participants	BG00059

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

Objective Response for HER2+ Patients (Best Objective Response a Patient Has Ever Experienced on Study)

To assess objective response, it is necessary to estimate the overall tumor burden at baseline to which subsequent measurements will be compared. The same method of assessment and the same technique should be used to characterize each lesion at baseline and during follow-up.

The best overall response based on RECIST is the best response recorded from registration until disease progression/recurrence, taking as reference for progressive disease the smallest measurements recorded since registration. The best response was determined based on the tumor responses in target and nontarget lesions, with or without new lesions. To be assigned a status of complete or partial response, changes in tumor measurements must be confirmed by repeat assessments performed no less than 4 weeks after the criteria for response are first met. To be assigned a status of stable disease, measurements must have met the stable disease criteria at least once after study entry at a minimum interval of 8 weeks.

HER2+ patients

Posted

Number

Participants

Assessed every 3 cycles during induction therapy and every 6 cycles during maintenance therapy until disease progression or up to 5 years

ID	Title	Description
OG000	Trastuzumab/Ixabepilone/Carboplatin	During the induction phase, patients were treated with Ixabepilone (BMS-247550) 15mg/m2 intravenously (IV) followed by carboplatin (AUC=2 IV) on days 1, 8 and 15 of a 28-day cycle for a maximum of 6 cycles. Trastuzumab was administered weekly (4mg/kg loading dose then 2mg/kg IV) starting on day 1. Routine premedication included H1 blocker (diphenhydramine 50 mg orally (PO) or IV), H2 blocker (ranitidine 150 mg PO or 50 mg IV or another equivalent H2 blocker), and at least a 5-HT3 antagonist and dexamethasone. After completion of 24 weekly trastuzumab doses (induction therapy), trastuzumab were given at a dose of 6 mg/kg IV every 3 weeks (maintenance therapy) beginning one week after the 24th weekly dose. Trastuzumab were repeated every 21 days until disease progression or prohibitive toxicity.

Units	Counts
Participants	OG00039

Title

Denominators

Categories

Complete Response

Title	Measurements
	OG0003

Partial Response

Title	Measurements
	OG00013

No Change/ Stable

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						Objective response rate	41			2-Sided	95	26	58				No	Superiority or Other

Secondary

Objective Response for All Treated Patients (the Best Response a Patient Has Ever Experienced on Study)

All treated patients

Posted

Number

Participants

Assessed every 3 cycles during induction therapy and every 6 cycles during maintenance therapy until disease progression or up to 5 years

ID	Title	Description
OG000	Trastuzumab/Ixabepilone/Carboplatin	During the induction phase, patients were treated with Ixabepilone (BMS-247550) 15mg/m2 intravenously (IV) followed by carboplatin (AUC=2 IV) on days 1, 8 and 15 of a 28-day cycle for a maximum of 6 cycles. Trastuzumab was administered weekly (4mg/kg loading dose then 2mg/kg IV) starting on day 1. Routine premedication included H1 blocker (diphenhydramine 50 mg orally (PO) or IV), H2 blocker (ranitidine 150 mg PO or 50 mg IV or another equivalent H2 blocker), and at least a 5-HT3 antagonist and dexamethasone. After completion of 24 weekly trastuzumab doses (induction therapy), trastuzumab were given at a dose of 6 mg/kg IV every 3 weeks (maintenance therapy) beginning one week after the 24th weekly dose. Trastuzumab were repeated every 21 days until disease progression or prohibitive toxicity.

Secondary

Time to Disease Progression for HER2+ Patients

This interval will be measured from the date of entry on the study to the appearance of new metastatic lesions or objective tumor progression based on RECIST. Patients progression-free at last follow-up were censored.

HER2+ patients

Posted

Median

95% Confidence Interval

Months

Assessed every 3 cycles during induction therapy and every 6 cycles during maintenance therapy until disease progression or up to 5 years

ID	Title	Description
OG000	Trastuzumab/Ixabepilone/Carboplatin	During the induction phase, patients were treated with Ixabepilone (BMS-247550) 15mg/m2 intravenously (IV) followed by carboplatin (AUC=2 IV) on days 1, 8 and 15 of a 28-day cycle for a maximum of 6 cycles. Trastuzumab was administered weekly (4mg/kg loading dose then 2mg/kg IV) starting on day 1. Routine premedication included H1 blocker (diphenhydramine 50 mg orally (PO) or IV), H2 blocker (ranitidine 150 mg PO or 50 mg IV or another equivalent H2 blocker), and at least a 5-HT3 antagonist and dexamethasone. After completion of 24 weekly trastuzumab doses (induction therapy), trastuzumab were given at a dose of 6 mg/kg IV every 3 weeks (maintenance therapy) beginning one week after the 24th weekly dose. Trastuzumab were repeated every 21 days until disease progression or prohibitive toxicity.

Units	Counts
Participants

Secondary

Time to Disease Progression for All Treated Patients

All treated patients

Posted

Median

95% Confidence Interval

Months

Assessed every 3 cycles during induction therapy and every 6 cycles during maintenance therapy until disease progression or up to 5 years

ID	Title	Description
OG000	Trastuzumab/Ixabepilone/Carboplatin	During the induction phase, patients were treated with Ixabepilone (BMS-247550) 15mg/m2 intravenously (IV) followed by carboplatin (AUC=2 IV) on days 1, 8 and 15 of a 28-day cycle for a maximum of 6 cycles. Trastuzumab was administered weekly (4mg/kg loading dose then 2mg/kg IV) starting on day 1. Routine premedication included H1 blocker (diphenhydramine 50 mg orally (PO) or IV), H2 blocker (ranitidine 150 mg PO or 50 mg IV or another equivalent H2 blocker), and at least a 5-HT3 antagonist and dexamethasone. After completion of 24 weekly trastuzumab doses (induction therapy), trastuzumab were given at a dose of 6 mg/kg IV every 3 weeks (maintenance therapy) beginning one week after the 24th weekly dose. Trastuzumab were repeated every 21 days until disease progression or prohibitive toxicity.

Units	Counts
Participants

Secondary

Time to Treatment Failure for HER2+ Patients

Time from study entry to the date at which a patient was removed from treatment due to progression, toxicity, refusal or death. If a patient was considered to be a major treatment violation or was taken off study as a non-protocol failure, the patient would be censored on the date he/she was removed from treatment.

HER2+ patients

Posted

Median

95% Confidence Interval

Months

Assessed every cycle until treatment discontinuation

ID	Title	Description
OG000	Trastuzumab/Ixabepilone/Carboplatin	During the induction phase, patients were treated with Ixabepilone (BMS-247550) 15mg/m2 intravenously (IV) followed by carboplatin (AUC=2 IV) on days 1, 8 and 15 of a 28-day cycle for a maximum of 6 cycles. Trastuzumab was administered weekly (4mg/kg loading dose then 2mg/kg IV) starting on day 1. Routine premedication included H1 blocker (diphenhydramine 50 mg orally (PO) or IV), H2 blocker (ranitidine 150 mg PO or 50 mg IV or another equivalent H2 blocker), and at least a 5-HT3 antagonist and dexamethasone. After completion of 24 weekly trastuzumab doses (induction therapy), trastuzumab were given at a dose of 6 mg/kg IV every 3 weeks (maintenance therapy) beginning one week after the 24th weekly dose. Trastuzumab were repeated every 21 days until disease progression or prohibitive toxicity.

Units	Counts
Participants

Secondary

Time to Treatment Failure for All Treated Patients

All treated patients

Posted

Median

95% Confidence Interval

Months

Assessed every cycle until treatment discontinuation

ID	Title	Description
OG000	Trastuzumab/Ixabepilone/Carboplatin	During the induction phase, patients were treated with Ixabepilone (BMS-247550) 15mg/m2 intravenously (IV) followed by carboplatin (AUC=2 IV) on days 1, 8 and 15 of a 28-day cycle for a maximum of 6 cycles. Trastuzumab was administered weekly (4mg/kg loading dose then 2mg/kg IV) starting on day 1. Routine premedication included H1 blocker (diphenhydramine 50 mg orally (PO) or IV), H2 blocker (ranitidine 150 mg PO or 50 mg IV or another equivalent H2 blocker), and at least a 5-HT3 antagonist and dexamethasone. After completion of 24 weekly trastuzumab doses (induction therapy), trastuzumab were given at a dose of 6 mg/kg IV every 3 weeks (maintenance therapy) beginning one week after the 24th weekly dose. Trastuzumab were repeated every 21 days until disease progression or prohibitive toxicity.

Units	Counts
Participants

Secondary

Kaplan-Meier Estimate of Overall Survival at 3 Years for HER2+ Patients

Survival estimate from the Kaplan-Meier curve of the proportion of patients alive at 3 years.

HER2+ patients

Posted

Number

95% Confidence Interval

Percentage of Participants

Assessed every 3 months for 2 years, then every 6 months for 3 years

ID	Title	Description
OG000	Trastuzumab/Ixabepilone/Carboplatin	During the induction phase, patients were treated with Ixabepilone (BMS-247550) 15mg/m2 intravenously (IV) followed by carboplatin (AUC=2 IV) on days 1, 8 and 15 of a 28-day cycle for a maximum of 6 cycles. Trastuzumab was administered weekly (4mg/kg loading dose then 2mg/kg IV) starting on day 1. Routine premedication included H1 blocker (diphenhydramine 50 mg orally (PO) or IV), H2 blocker (ranitidine 150 mg PO or 50 mg IV or another equivalent H2 blocker), and at least a 5-HT3 antagonist and dexamethasone. After completion of 24 weekly trastuzumab doses (induction therapy), trastuzumab were given at a dose of 6 mg/kg IV every 3 weeks (maintenance therapy) beginning one week after the 24th weekly dose. Trastuzumab were repeated every 21 days until disease progression or prohibitive toxicity.

Units	Counts
Participants

Secondary

Kaplan-Meier Estimate of Overall Survival at 3 Years for All Treated Patients

Survival estimate from the Kaplan-Meier curve of the proportion of patients alive at 3 years.

All treated patients

Posted

Number

95% Confidence Interval

Percentage of Participants

Assessed every 3 months for 2 years, then every 6 months for 3 years

ID	Title	Description
OG000	Trastuzumab/Ixabepilone/Carboplatin	During the induction phase, patients were treated with Ixabepilone (BMS-247550) 15mg/m2 intravenously (IV) followed by carboplatin (AUC=2 IV) on days 1, 8 and 15 of a 28-day cycle for a maximum of 6 cycles. Trastuzumab was administered weekly (4mg/kg loading dose then 2mg/kg IV) starting on day 1. Routine premedication included H1 blocker (diphenhydramine 50 mg orally (PO) or IV), H2 blocker (ranitidine 150 mg PO or 50 mg IV or another equivalent H2 blocker), and at least a 5-HT3 antagonist and dexamethasone. After completion of 24 weekly trastuzumab doses (induction therapy), trastuzumab were given at a dose of 6 mg/kg IV every 3 weeks (maintenance therapy) beginning one week after the 24th weekly dose. Trastuzumab were repeated every 21 days until disease progression or prohibitive toxicity.

Units	Counts
Participants

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	Trastuzumab/Ixabepilone/Carboplatin	During the induction phase, patients were treated with Ixabepilone (BMS-247550) 15mg/m2 intravenously (IV) followed by carboplatin (AUC=2 IV) on days 1, 8 and 15 of a 28-day cycle for a maximum of 6 cycles. Trastuzumab was administered weekly (4mg/kg loading dose then 2mg/kg IV) starting on day 1. Routine premedication included H1 blocker (diphenhydramine 50 mg orally (PO) or IV), H2 blocker (ranitidine 150 mg PO or 50 mg IV or another equivalent H2 blocker), and at least a 5-HT3 antagonist and dexamethasone. After completion of 24 weekly trastuzumab doses (induction therapy), trastuzumab were given at a dose of 6 mg/kg IV every 3 weeks (maintenance therapy) beginning one week after the 24th weekly dose. Trastuzumab were repeated every 21 days until disease progression or prohibitive toxicity.			39	59	59	59

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Allergic reaction	Immune system disorders	CTCAE (3.0)	Systematic Assessment	EG0002 affected59 at risk
Anemia	Blood and lymphatic system disorders	CTCAE (3.0)	Systematic Assessment	EG0007 affected59 at risk
Leukopenia	Investigations	CTCAE (3.0)	Systematic Assessment	EG00019 affected59 at risk
Neutropenia	Investigations	CTCAE (3.0)	Systematic Assessment	EG00029 affected59 at risk
Thrombocytopenia	Investigations	CTCAE (3.0)	Systematic Assessment	EG0008 affected59 at risk
Hematologic-other	Blood and lymphatic system disorders	CTCAE (3.0)	Systematic Assessment	EG0001 affected59 at risk
Hypertension	Vascular disorders	CTCAE (3.0)	Systematic Assessment	EG0001 affected59 at risk
Hypotension	Vascular disorders	CTCAE (3.0)	Systematic Assessment	EG0001 affected59 at risk
Fatigue	General disorders	CTCAE (3.0)	Systematic Assessment	EG0007 affected59 at risk
Weight loss	Investigations	CTCAE (3.0)	Systematic Assessment	EG0001 affected59 at risk
Death NOS	General disorders	CTCAE (3.0)	Systematic Assessment	EG0001 affected59 at risk
Anorexia	Metabolism and nutrition disorders	CTCAE (3.0)	Systematic Assessment	EG0003 affected59 at risk
Dehydration	Metabolism and nutrition disorders	CTCAE (3.0)	Systematic Assessment	EG0003 affected59 at risk
Diarrhea w/o prior colostomy	Gastrointestinal disorders	CTCAE (3.0)	Systematic Assessment	EG0004 affected59 at risk
Nausea	Gastrointestinal disorders	CTCAE (3.0)	Systematic Assessment	EG0004 affected59 at risk
Vomiting	Gastrointestinal disorders	CTCAE (3.0)	Systematic Assessment	EG0002 affected59 at risk
Infection with Grade 0-2 neutrophils, urinary tract	Infections and infestations	CTCAE (3.0)	Systematic Assessment	EG0002 affected59 at risk
Alkaline phosphatase increased	Investigations	CTCAE (3.0)	Systematic Assessment	EG0001 affected59 at risk
AST increased	Investigations	CTCAE (3.0)	Systematic Assessment	EG0001 affected59 at risk
Hyperglycemia	Metabolism and nutrition disorders	CTCAE (3.0)	Systematic Assessment	EG0002 affected59 at risk
Hypokalemia	Metabolism and nutrition disorders	CTCAE (3.0)	Systematic Assessment	EG0001 affected59 at risk
Hypernatremia	Metabolism and nutrition disorders	CTCAE (3.0)	Systematic Assessment	EG0001 affected59 at risk
Hyponatremia	Metabolism and nutrition disorders	CTCAE (3.0)	Systematic Assessment	EG0001 affected59 at risk
Nonneuropathic generalized weakness	Musculoskeletal and connective tissue disorders	CTCAE (3.0)	Systematic Assessment	EG0001 affected59 at risk
Encephalopathy	Nervous system disorders	CTCAE (3.0)	Systematic Assessment	EG0001 affected59 at risk
Neuropathy-sensory	Nervous system disorders	CTCAE (3.0)	Systematic Assessment	EG0004 affected59 at risk
Syncope	Nervous system disorders	CTCAE (3.0)	Systematic Assessment	EG0001 affected59 at risk
Abdomen, pain	Gastrointestinal disorders	CTCAE (3.0)	Systematic Assessment	EG0001 affected59 at risk
Extremity-limb, pain	Musculoskeletal and connective tissue disorders	CTCAE (3.0)	Systematic Assessment	EG0001 affected59 at risk
Joint, pain	Musculoskeletal and connective tissue disorders	CTCAE (3.0)	Systematic Assessment	EG0001 affected59 at risk
Muscle, pain	Musculoskeletal and connective tissue disorders	CTCAE (3.0)	Systematic Assessment	EG0001 affected59 at risk
Tumor pain	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	CTCAE (3.0)	Systematic Assessment	EG0001 affected59 at risk
Dyspnea	Respiratory, thoracic and mediastinal disorders	CTCAE (3.0)	Systematic Assessment	EG0001 affected59 at risk
Thrombosis/thrombus/embolism	Vascular disorders	CTCAE (3.0)	Systematic Assessment	EG0002 affected59 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Allergic reaction	Immune system disorders	CTCAE (3.0)	Systematic Assessment	EG0008 affected59 at risk
Anemia	Blood and lymphatic system disorders	CTCAE (3.0)	Systematic Assessment	EG00055 affected59 at risk
Leukopenia	Investigations	CTCAE (3.0)	Systematic Assessment	EG00054 affected59 at risk
Neutropenia	Investigations	CTCAE (3.0)	Systematic Assessment	EG00044 affected59 at risk
Thrombocytopenia	Investigations	CTCAE (3.0)	Systematic Assessment	EG00037 affected59 at risk
Left ventricular systolic dysfunction	Cardiac disorders	CTCAE (3.0)	Systematic Assessment	EG0006 affected59 at risk
Fatigue	General disorders	CTCAE (3.0)	Systematic Assessment	EG00051 affected59 at risk
Fever w/o neutropenia	General disorders	CTCAE (3.0)	Systematic Assessment	EG0005 affected59 at risk
Insomnia	Psychiatric disorders	CTCAE (3.0)	Systematic Assessment	EG0007 affected59 at risk
Rigors/chills	General disorders	CTCAE (3.0)	Systematic Assessment	EG0003 affected59 at risk
Sweating	Skin and subcutaneous tissue disorders	CTCAE (3.0)	Systematic Assessment	EG0003 affected59 at risk
Weight loss	Investigations	CTCAE (3.0)	Systematic Assessment	EG00010 affected59 at risk
Dry skin	Skin and subcutaneous tissue disorders	CTCAE (3.0)	Systematic Assessment	EG0004 affected59 at risk
Alopecia	Skin and subcutaneous tissue disorders	CTCAE (3.0)	Systematic Assessment	EG00033 affected59 at risk
Pruritus/itching	Skin and subcutaneous tissue disorders	CTCAE (3.0)	Systematic Assessment	EG0004 affected59 at risk
Rash/desquamation	Skin and subcutaneous tissue disorders	CTCAE (3.0)	Systematic Assessment	EG00010 affected59 at risk
Hot flashes	Vascular disorders	CTCAE (3.0)	Systematic Assessment	EG0003 affected59 at risk
Anorexia	Metabolism and nutrition disorders	CTCAE (3.0)	Systematic Assessment	EG00022 affected59 at risk
Constipation	Gastrointestinal disorders	CTCAE (3.0)	Systematic Assessment	EG00024 affected59 at risk
Diarrhea w/o prior colostomy	Gastrointestinal disorders	CTCAE (3.0)	Systematic Assessment	EG00033 affected59 at risk
Dyspepsia	Gastrointestinal disorders	CTCAE (3.0)	Systematic Assessment	EG00011 affected59 at risk
Muco/stomatitis by exam, oral cavity	Gastrointestinal disorders	CTCAE (3.0)	Systematic Assessment	EG00017 affected59 at risk
Nausea	Gastrointestinal disorders	CTCAE (3.0)	Systematic Assessment	EG00042 affected59 at risk
Taste disturbance	Nervous system disorders	CTCAE (3.0)	Systematic Assessment	EG00021 affected59 at risk
Vomiting	Gastrointestinal disorders	CTCAE (3.0)	Systematic Assessment	EG00020 affected59 at risk
Nose, hemorrhage	Respiratory, thoracic and mediastinal disorders	CTCAE (3.0)	Systematic Assessment	EG0005 affected59 at risk
Infection with Grade 0-2 neutrophils, skin	Infections and infestations	CTCAE (3.0)	Systematic Assessment	EG0003 affected59 at risk
Infection with Grade 0-2 neutrophils, urinary tract	Infections and infestations	CTCAE (3.0)	Systematic Assessment	EG0003 affected59 at risk
Edema limb	General disorders	CTCAE (3.0)	Systematic Assessment	EG00010 affected59 at risk
Hypoalbuminemia	Metabolism and nutrition disorders	CTCAE (3.0)	Systematic Assessment	EG0003 affected59 at risk
Alkaline phosphatase increased	Investigations	CTCAE (3.0)	Systematic Assessment	EG00017 affected59 at risk
ALT increased	Investigations	CTCAE (3.0)	Systematic Assessment	EG00024 affected59 at risk
AST increased	Investigations	CTCAE (3.0)	Systematic Assessment	EG00020 affected59 at risk
Bilirubin increased	Investigations	CTCAE (3.0)	Systematic Assessment	EG0004 affected59 at risk
Creatinine increased	Investigations	CTCAE (3.0)	Systematic Assessment	EG0004 affected59 at risk
Hyperglycemia	Metabolism and nutrition disorders	CTCAE (3.0)	Systematic Assessment	EG00028 affected59 at risk
Hypoglycemia	Metabolism and nutrition disorders	CTCAE (3.0)	Systematic Assessment	EG0003 affected59 at risk
Hypomagnesemia	Metabolism and nutrition disorders	CTCAE (3.0)	Systematic Assessment	EG0003 affected59 at risk
Hypokalemia	Metabolism and nutrition disorders	CTCAE (3.0)	Systematic Assessment	EG0004 affected59 at risk
Dizziness	Nervous system disorders	CTCAE (3.0)	Systematic Assessment	EG0007 affected59 at risk
Anxiety	Psychiatric disorders	CTCAE (3.0)	Systematic Assessment	EG0003 affected59 at risk
Neuropathy-motor	Nervous system disorders	CTCAE (3.0)	Systematic Assessment	EG0004 affected59 at risk
Neuropathy-sensory	Nervous system disorders	CTCAE (3.0)	Systematic Assessment	EG00036 affected59 at risk
Abdomen, pain	Gastrointestinal disorders	CTCAE (3.0)	Systematic Assessment	EG0006 affected59 at risk
Back, pain	Musculoskeletal and connective tissue disorders	CTCAE (3.0)	Systematic Assessment	EG0003 affected59 at risk
Chest/thoracic pain NOS	General disorders	CTCAE (3.0)	Systematic Assessment	EG0005 affected59 at risk
Head/headache	Nervous system disorders	CTCAE (3.0)	Systematic Assessment	EG0008 affected59 at risk
Joint, pain	Musculoskeletal and connective tissue disorders	CTCAE (3.0)	Systematic Assessment	EG00014 affected59 at risk
Muscle, pain	Musculoskeletal and connective tissue disorders	CTCAE (3.0)	Systematic Assessment	EG00016 affected59 at risk
Cough	Respiratory, thoracic and mediastinal disorders	CTCAE (3.0)	Systematic Assessment	EG0006 affected59 at risk
Dyspnea	Respiratory, thoracic and mediastinal disorders	CTCAE (3.0)	Systematic Assessment	EG00011 affected59 at risk

ID	Term
D018567	Breast Neoplasms, Male
D001943	Breast Neoplasms

ID	Term
D009371	Neoplasms by Site
D009369	Neoplasms
D001941	Breast Diseases
D012871	Skin Diseases
D017437	Skin and Connective Tissue Diseases

ID	Term
D061067	Antibodies, Monoclonal, Humanized
D000911	Antibodies, Monoclonal
D000906	Antibodies
D007136	Immunoglobulins
D007162	Immunoproteins
D001798	Blood Proteins
D011506	Proteins
D000602	Amino Acids, Peptides, and Proteins
D012712	Serum Globulins
D005916	Globulins
D056831	Coordination Complexes
D009930	Organic Chemicals