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June 2008 Breast Committee CALGB 40101
Breast - 1
CALGB/CTSU 40101
Cyclophosphamide and Doxorubicin (CA x 4 cycles) versus Paclitaxel (4 cycles) as Adjuvant Therapy
for Breast Cancer in Women with 0-3 Positive Axillary Lymph Nodes:
A Phase III Randomized Study
Activated: May 15, 2002 Study Chairpersons: L. Shulman CALGB
Accrual as of 4/17/2008: 3200 S. Martino SWOG
Projected Accrual: 4646 E. Perez NCCTG
Projected Closure April 2012 R. O’Regan ECOG
Coordinating Group: CALGB Statisticians: D. Berry CALGB
Current Protocol Update: #8, February 15, 2008 C. Cirrincione CALGB
Data Coordinator: R. Heinze CALGB
SCHEMA
§ Administration of filgrastim, sargramostim or pegfilgrastim is recommended.
‡ Patients who have undergone lumpectomy must receive XRT according to local institutional standards. Patients who
have undergone mastectomy may receive chest wall and nodal XRT.
* Aromatase inhibitors may be substituted for tamoxifen in postmenopausal women.
Objectives
Primary
1. To determine the equivalence of paclitaxel given every
2 weeks with CA given every 2 weeks as adjuvant
therapy for women with 0-3 positive axillary lymph
nodes for disease-free survival.
2. To determine if longer therapy, 12 weeks, is superior to
shorter therapy, 8 weeks, of either CA or paclitaxel for
disease-free survival for women with primary breast
cancer with 0-3 positive axillary lymph nodes.
Secondary 1. To determine the equivalence of paclitaxel given every
2 weeks with CA given every 2 weeks, and the
potential superiority of longer vs. shorter therapy, in
relation to overall survival, local control (regardless of
metastatic status) and time to distant metastases
(regardless of local recurrence status).
2. To compare toxicities of short and long course CA and
paclitaxel as adjuvant therapy for women with 0-3
positive axillary lymph node breast cancer.
3. To determine the effect of long and short course CA
and paclitaxel on the induction of menopause for pre-
menopausal patients.
4. To assess the discrepancy of myelosuppression among
the common MDR1 haplotypes in the CA treatment
arm.
5. To assess the effect of MDR1 haplotypes on DFS
adjusted for treatment.
6. Exploratory analysis of the effect of CYP3A5,
CYP2C8 and CYP2B6 polymorphisms on DFS and
toxicity.
Pr im a r y O p er a b l e Ax i ll a ry Lym p h No d e 0 -3 Po s it i ve
B r ea s t C an ce r
S t r a t i fi ca t i o n Fa c t o rs P r e or Po s t M en o p a u s a l E R / PgR P os / Neg / U n k HE R 2 s t a tu s
Po s / Ne g/ U n k
R A N D O M I Z
E
S t a n d a rd Ch em o th er a p y C A Cy clo p h o s p h a m id e 6 0 0 m g/ m 2 An d D o x or u b i cin 6 0 m g / m 2 q 1 4 d a ys
x 4 cyc le s§
S in gl e Age n t Pa c li t a xe l 1 7 5 m g / m 2 q
1 4 d a y s x 4 c yc les §
XRT ‡ if
in d ic a t ed
Ta m o x ifen * x 5 y ea r s
r e com me n d ed If E R a n d / o r
PgR Po s i t iv e
Tr a s t u zu m a b * w il l b e a l lo w ed fo r p t s wh os e t u m o rs o ve re x p re s s
H E R2
June 2008 Breast Committee CALGB 40101
Breast - 2
Eligibility Criteria
• Histologically confirmed invasive carcinoma of the
female breast
• “High risk” node-negative breast cancer that warrants
chemotherapy
• ER/PgR positive, negative or unknown
• HER2 positive, negative, or unknown; recommended
that patients with HER2 positive disease receive
trastuzumab
• Negative tumor margins for invasive cancer and DCIS;
LCIS acceptable at the margin
• Multicentric breast cancer allowed if resected w/neg
margins and axillary nodes negative
• Pts. must be registered < 84 days from MRM or
lumpectomy
• No previous trastuzumab, chemo or hormonal therapy
except for tamoxifen
• No locally advanced or inflammatory breast cancer or
involvement of dermal lymphatics
• Bilateral, synchronous breast cancers are eligible
• Disease free > 5 years for prior malignancies
• Age > 18 years
• CTC Performance Status 0-1
• Non-pregnant and not nursing
• No concomitant exogenous hormone therapy
• Tamoxifen or another selective estrogen receptor
modulator (SERM) for breast cancer prevention is
allowed
• Adequate organ function; no active CHF; no MI < 6
months from the time of registration.
• Patients may be enrolled in adjuvant bisphosphonate or
adjuvant hormonal studies concurrently with protocol
therapy
Required Laboratory Values
ANC >1000/mm3
Platelet Count > 100,000/mm3
Creatinine < 2.0 mg/dl
Bilirubin < 1.5 x ULN
Administrative Comments
This is an intergroup study coordinated by the CALGB
that was activated on May 15, 2002. It has also been
opened within the CTSU.
A study update in October 2005 broadened eligibility to
include patients with 1-3 positive axillary nodes, and to
allow patients with HER2-positive tumors a 52-week
course of adjuvant trastuzumab. HER2 tumor status was
therefore added as a stratification factor.
In February 2008 accrual was closed to the two 6-cycle
arms. Accrual continues with equally weighted
randomization to the remaining two arms of 4 cycles
each. The study schema and title have been modified to
reflect this change.
Accrual
As of April 17, 2008 the total enrollment was 3200
patients, of which the CTSU enrolled 1767 (55%).
Accrual by Institution
For Period 5/15/2002 Through 4/17/2008
Main/At-Large
Member Affiliate Total
CCHLTH 81 16 97
CHAPEL 31 46 77
CHICAGO 4 26 30
DARTMOUTH 9 23 32
DUKE 26 85 111
FARBER 30 90 120
GMOG 0 1 1
GRAND 10 18 28
GRENVIL 4 0 4
HOACNY 6 29 35
ILLINOIS 4 17 21
IORA 7 33 40
IOWA 5 5 10
KCCOP 5 0 5
MARYLAND 19 9 28
MGH 2 0 2
MIAMI 16 8 24
MINNESOTA 10 11 21
MO/EFCC 17 4 21
MOBAPT 15 8 23
MSH 2 42 44
MSKCC 10 0 10
MVCC 1 37 38
NCRF 0 22 22
NEBRASKA 4 79 83
NHOH 19 19 38
NICRC 9 11 20
OKLAHOMA 2 5 7
OSUMC 97 0 97
RIH 6 4 10
RPCI 15 3 18
SECCC 0 121 121
SIBLEY 7 0 7
SYRACUSE 7 7 14
UCSD 25 14 39
UMMS 9 6 15
UTEXAS 12 0 12
VCC 19 1 20
June 2008 Breast Committee CALGB 40101
Breast - 3
Main/At-Large
Member Affiliate Total
WASH-BARN 9 17 26
WEILL 0 2 2
WFUSM 27 0 27
WPENN 1 1 2
WRAMC 31 0 31
CALGB Total 613 820 1433
CTSU 1767
Total Accrual 3200
Accrual by Month
Adverse Events
A. During Protocol Therapy
The following table shows the highest grade of toxicity, which was possibly, probably or definitely due to treatment,
which occurred during the interval from the start of protocol therapy to 6 weeks after ending protocol treatment. Data
were available for 3008 patients.
The incidence of any hematologic toxicity of Grade 3 or higher was considerably higher for the CA arms than for the T
arms. The incidence of any non-hematologic toxicity of Grade 3 or higher was slightly higher for the 6-cycle regimens
than for the 4-cycle arms.
There were two Grade 5 (lethal) toxicities. Both patients died from cardiac-related causes; both were on CA regimens.
The first patient died from a myocardial infarction (Grade 5 – Cardiac-other) 96 days after beginning CAx4, just after
completing all protocol treatment. The second patient died four months after beginning CAx6 protocol therapy of Grade
5 left ventricular failure.
There were few Grade 4 toxicities. The most frequent were neutropenia and leukopenia in the two CA arms. All other
Grade 4 toxicities occurred with a frequency of ≤ 1%.
The largest differences in the occurrence of Grade 3 or higher toxicities between the CA and T regimens were
neutropenia, leukopenia, febrile neutropenia and sensory neuropathy
Grade of Adverse Event
Arm 3-Severe 4-LifeThr 5-Lethal Total
n (%) n (%) n (%)
Hematologic Adverse Events
Blood/Bone Marrow
Blood/Bone Marrow - Other CAx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 761
CAx6 1 ( 0%) 0 ( 0%) 0 ( 0%) 741
Tx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 761
Tx6 0 ( 0%) 0 ( 0%) 0 ( 0%) 745
2002 2003 2004 2005 2006 2007 2008 Total
Jan -- 47 72 62 48 32 31 292
Feb -- 37 75 59 48 38 18 275
Mar -- 44 67 70 59 46 24 310
Apr -- 39 71 68 46 42 24 290
May 0 42 71 69 50 54 -- 286
Jun 1 48 63 56 51 50 -- 269
Jul 6 47 54 54 38 33 -- 232
Aug 10 38 50 46 44 44 -- 232
Sep 16 45 54 63 40 33 -- 251
Oct 23 58 59 68 37 42 -- 287
Nov 20 45 56 39 27 30 -- 217
Dec 37 52 57 42 35 36 -- 259
Total
l 113 542 749 696 523 480 97 3200
June 2008 Breast Committee CALGB 40101
Breast - 4
Grade of Adverse Event
Arm 3-Severe 4-LifeThr 5-Lethal Total
n (%) n (%) n (%)
Hemoglobin CAx4 18 ( 2%) 0 ( 0%) 0 ( 0%) 761
CAx6 47 ( 6%) 2 ( 0%) 0 ( 0%) 741
Tx4 1 ( 0%) 0 ( 0%) 0 ( 0%) 761
Tx6 4 ( 1%) 1 ( 0%) 0 ( 0%) 745
Leukocytes (total WBC) CAx4 78 ( 10%) 65 ( 9%) 0 ( 0%) 761
CAx6 97 ( 13%) 101 ( 14%) 0 ( 0%) 741
Tx4 6 ( 1%) 3 ( 0%) 0 ( 0%) 761
Tx6 7 ( 1%) 0 ( 0%) 0 ( 0%) 745
Lymphopenia CAx4 8 ( 1%) 0 ( 0%) 0 ( 0%) 761
CAx6 9 ( 1%) 1 ( 0%) 0 ( 0%) 741
Tx4 3 ( 0%) 0 ( 0%) 0 ( 0%) 761
Tx6 1 ( 0%) 0 ( 0%) 0 ( 0%) 745
Neutrophils/granulocytes (ANC/AGC) CAx4 69 ( 9%) 129 ( 17%) 0 ( 0%) 761
CAx6 79 ( 11%) 169 ( 23%) 0 ( 0%) 741
Tx4 14 ( 2%) 9 ( 1%) 0 ( 0%) 761
Tx6 14 ( 2%) 4 ( 1%) 0 ( 0%) 745
Platelets CAx4 9 ( 1%) 2 ( 0%) 0 ( 0%) 761
CAx6 24 ( 3%) 8 ( 1%) 0 ( 0%) 741
Tx4 1 ( 0%) 0 ( 0%) 0 ( 0%) 761
Tx6 0 ( 0%) 0 ( 0%) 0 ( 0%) 745
Transfusion: Platelets CAx4 1 ( 0%) 0 ( 0%) 0 ( 0%) 761
CAx6 1 ( 0%) 0 ( 0%) 0 ( 0%) 741
Tx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 761
Tx6 0 ( 0%) 0 ( 0%) 0 ( 0%) 745
Transfusion: pRBCs CAx4 3 ( 0%) 0 ( 0%) 0 ( 0%) 761
CAx6 12 ( 2%) 0 ( 0%) 0 ( 0%) 741
Tx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 761
Tx6 3 ( 0%) 0 ( 0%) 0 ( 0%) 745
SUMMARY
Maximum Hematologic AE CAx4 84 ( 11%) 134 ( 18%) 0 ( 0%) 761
CAx6 97 ( 13%) 181 ( 24%) 0 ( 0%) 741
Tx4 21 ( 3%) 9 ( 1%) 0 ( 0%) 761
Tx6 24 ( 3%) 5 ( 1%) 0 ( 0%) 745
Non-Hematologic Adverse Events
Allergy/Immunology
Allergic reaction/hypersensitivity CAx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 761
CAx6 1 ( 0%) 1 ( 0%) 0 ( 0%) 741
Tx4 12 ( 2%) 0 ( 0%) 0 ( 0%) 761
Tx6 11 ( 1%) 1 ( 0%) 0 ( 0%) 745
Cardiac Arrhythmia
June 2008 Breast Committee CALGB 40101
Breast - 5
Grade of Adverse Event
Arm 3-Severe 4-LifeThr 5-Lethal Total
n (%) n (%) n (%)
Cardiac Arrhythmia - Other CAx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 761
CAx6 1 ( 0%) 0 ( 0%) 0 ( 0%) 741
Tx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 761
Tx6 2 ( 0%) 2 ( 0%) 0 ( 0%) 745
Supraventricular and nodal arrhythmia CAx4 0 ( 0%) 1 ( 0%) 0 ( 0%) 761
CAx6 0 ( 0%) 0 ( 0%) 0 ( 0%) 741
Tx4 1 ( 0%) 0 ( 0%) 0 ( 0%) 761
Tx6 0 ( 0%) 1 ( 0%) 0 ( 0%) 745
Cardiac General
Cardiac troponin T (cTnT) CAx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 761
CAx6 1 ( 0%) 0 ( 0%) 0 ( 0%) 741
Tx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 761
Tx6 0 ( 0%) 0 ( 0%) 0 ( 0%) 745
Left ventricular systolic dysfunction CAx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 761
CAx6 2 ( 0%) 2 ( 0%) 1 ( 0%) 741
Tx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 761
Tx6 1 ( 0%) 0 ( 0%) 0 ( 0%) 745
Restrictive cardiomyopathy CAx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 761
CAx6 1 ( 0%) 0 ( 0%) 0 ( 0%) 741
Tx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 761
Tx6 0 ( 0%) 0 ( 0%) 0 ( 0%) 745
Cardiovascular (Arrhythmias)
Vasovagal episode CAx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 761
CAx6 0 ( 0%) 0 ( 0%) 0 ( 0%) 741
Tx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 761
Tx6 1 ( 0%) 0 ( 0%) 0 ( 0%) 745
Cardiovascular (General)
Cardiovascular/General-Other CAx4 0 ( 0%) 0 ( 0%) 1 ( 0%) 761
CAx6 0 ( 0%) 0 ( 0%) 0 ( 0%) 741
Tx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 761
Tx6 1 ( 0%) 0 ( 0%) 0 ( 0%) 745
Hypertension CAx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 761
CAx6 0 ( 0%) 0 ( 0%) 0 ( 0%) 741
Tx4 5 ( 1%) 0 ( 0%) 0 ( 0%) 761
Tx6 4 ( 1%) 0 ( 0%) 0 ( 0%) 745
Hypotension CAx4 1 ( 0%) 1 ( 0%) 0 ( 0%) 761
CAx6 3 ( 0%) 0 ( 0%) 0 ( 0%) 741
Tx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 761
Tx6 1 ( 0%) 0 ( 0%) 0 ( 0%) 745
Constitutional Sym
June 2008 Breast Committee CALGB 40101
Breast - 6
Grade of Adverse Event
Arm 3-Severe 4-LifeThr 5-Lethal Total
n (%) n (%) n (%)
Constitutional Symptoms-Other CAx4 1 ( 0%) 0 ( 0%) 0 ( 0%) 761
CAx6 0 ( 0%) 0 ( 0%) 0 ( 0%) 741
Tx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 761
Tx6 0 ( 0%) 0 ( 0%) 0 ( 0%) 745
Fatigue (asthenia, lethargy, malaise) CAx4 15 ( 2%) 0 ( 0%) 0 ( 0%) 761
CAx6 40 ( 5%) 3 ( 0%) 0 ( 0%) 741
Tx4 4 ( 1%) 1 ( 0%) 0 ( 0%) 761
Tx6 18 ( 2%) 0 ( 0%) 0 ( 0%) 745
Insomnia CAx4 1 ( 0%) 0 ( 0%) 0 ( 0%) 761
CAx6 0 ( 0%) 0 ( 0%) 0 ( 0%) 741
Tx4 2 ( 0%) 0 ( 0%) 0 ( 0%) 761
Tx6 1 ( 0%) 0 ( 0%) 0 ( 0%) 745
Dermatology/Skin
Dermatology/Skin-Other CAx4 2 ( 0%) 0 ( 0%) 0 ( 0%) 761
CAx6 0 ( 0%) 0 ( 0%) 0 ( 0%) 741
Tx4 2 ( 0%) 0 ( 0%) 0 ( 0%) 761
Tx6 0 ( 0%) 0 ( 0%) 0 ( 0%) 745
Nail changes CAx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 761
CAx6 1 ( 0%) 0 ( 0%) 0 ( 0%) 741
Tx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 761
Tx6 0 ( 0%) 0 ( 0%) 0 ( 0%) 745
Pruritus CAx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 761
CAx6 0 ( 0%) 0 ( 0%) 0 ( 0%) 741
Tx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 761
Tx6 2 ( 0%) 0 ( 0%) 0 ( 0%) 745
Pruritus/itching CAx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 761
CAx6 0 ( 0%) 0 ( 0%) 0 ( 0%) 741
Tx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 761
Tx6 1 ( 0%) 0 ( 0%) 0 ( 0%) 745
Radiation dermatitis CAx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 761
CAx6 0 ( 0%) 0 ( 0%) 0 ( 0%) 741
Tx4 1 ( 0%) 0 ( 0%) 0 ( 0%) 761
Tx6 0 ( 0%) 0 ( 0%) 0 ( 0%) 745
Rash/desquamation CAx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 761
CAx6 1 ( 0%) 0 ( 0%) 0 ( 0%) 741
Tx4 1 ( 0%) 0 ( 0%) 0 ( 0%) 761
Tx6 6 ( 1%) 0 ( 0%) 0 ( 0%) 745
Rash: hand-foot skin reaction CAx4 2 ( 0%) 0 ( 0%) 0 ( 0%) 761
CAx6 8 ( 1%) 0 ( 0%) 0 ( 0%) 741
Tx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 761
June 2008 Breast Committee CALGB 40101
Breast - 7
Grade of Adverse Event
Arm 3-Severe 4-LifeThr 5-Lethal Total
n (%) n (%) n (%)
Tx6 1 ( 0%) 0 ( 0%) 0 ( 0%) 745
Wound-infectious CAx4 1 ( 0%) 0 ( 0%) 0 ( 0%) 761
CAx6 4 ( 1%) 0 ( 0%) 0 ( 0%) 741
Tx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 761
Tx6 0 ( 0%) 0 ( 0%) 0 ( 0%) 745
Endocrine
Hot flashes/flushes CAx4 1 ( 0%) 0 ( 0%) 0 ( 0%) 761
CAx6 0 ( 0%) 0 ( 0%) 0 ( 0%) 741
Tx4 1 ( 0%) 0 ( 0%) 0 ( 0%) 761
Tx6 0 ( 0%) 0 ( 0%) 0 ( 0%) 745
Gastrointestinal
Anorexia CAx4 4 ( 1%) 0 ( 0%) 0 ( 0%) 761
CAx6 3 ( 0%) 0 ( 0%) 0 ( 0%) 741
Tx4 1 ( 0%) 0 ( 0%) 0 ( 0%) 761
Tx6 0 ( 0%) 0 ( 0%) 0 ( 0%) 745
Colitis CAx4 1 ( 0%) 0 ( 0%) 0 ( 0%) 761
CAx6 2 ( 0%) 0 ( 0%) 0 ( 0%) 741
Tx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 761
Tx6 0 ( 0%) 0 ( 0%) 0 ( 0%) 745
Constipation CAx4 1 ( 0%) 0 ( 0%) 0 ( 0%) 761
CAx6 2 ( 0%) 0 ( 0%) 0 ( 0%) 741
Tx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 761
Tx6 0 ( 0%) 0 ( 0%) 0 ( 0%) 745
Dehydration CAx4 7 ( 1%) 1 ( 0%) 0 ( 0%) 761
CAx6 7 ( 1%) 1 ( 0%) 0 ( 0%) 741
Tx4 1 ( 0%) 0 ( 0%) 0 ( 0%) 761
Tx6 1 ( 0%) 0 ( 0%) 0 ( 0%) 745
Diarrhea patients without colostomy CAx4 4 ( 1%) 1 ( 0%) 0 ( 0%) 761
CAx6 10 ( 1%) 0 ( 0%) 0 ( 0%) 741
Tx4 12 ( 2%) 0 ( 0%) 0 ( 0%) 761
Tx6 10 ( 1%) 0 ( 0%) 0 ( 0%) 745
Dysphagia esophagitis odynophagia
(painful
CAx4 7 ( 1%) 0 ( 0%) 0 ( 0%) 761
CAx6 0 ( 0%) 0 ( 0%) 0 ( 0%) 741
Tx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 761
Tx6 0 ( 0%) 0 ( 0%) 0 ( 0%) 745
Dysphagia (difficulty swallowing) CAx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 761
CAx6 1 ( 0%) 0 ( 0%) 0 ( 0%) 741
Tx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 761
Tx6 0 ( 0%) 0 ( 0%) 0 ( 0%) 745
Gastrointestinal-Other CAx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 761
June 2008 Breast Committee CALGB 40101
Breast - 8
Grade of Adverse Event
Arm 3-Severe 4-LifeThr 5-Lethal Total
n (%) n (%) n (%)
CAx6 1 ( 0%) 0 ( 0%) 0 ( 0%) 741
Tx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 761
Tx6 0 ( 0%) 0 ( 0%) 0 ( 0%) 745
Heartburn/dyspepsia CAx4 2 ( 0%) 0 ( 0%) 0 ( 0%) 761
CAx6 3 ( 0%) 0 ( 0%) 0 ( 0%) 741
Tx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 761
Tx6 0 ( 0%) 0 ( 0%) 0 ( 0%) 745
Mucositis/stomatitis (clinical exam) CAx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 761
CAx6 1 ( 0%) 0 ( 0%) 0 ( 0%) 741
Tx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 761
Tx6 0 ( 0%) 0 ( 0%) 0 ( 0%) 745
Mucositis/stomatitis
(functional/symptomatic)
CAx4 9 ( 1%) 0 ( 0%) 0 ( 0%) 761
CAx6 18 ( 2%) 1 ( 0%) 0 ( 0%) 741
Tx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 761
Tx6 0 ( 0%) 0 ( 0%) 0 ( 0%) 745
Nausea CAx4 23 ( 3%) 1 ( 0%) 0 ( 0%) 761
CAx6 24 ( 3%) 0 ( 0%) 0 ( 0%) 741
Tx4 5 ( 1%) 1 ( 0%) 0 ( 0%) 761
Tx6 4 ( 1%) 0 ( 0%) 0 ( 0%) 745
Pancreatitis CAx4 1 ( 0%) 0 ( 0%) 0 ( 0%) 761
CAx6 1 ( 0%) 0 ( 0%) 0 ( 0%) 741
Tx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 761
Tx6 0 ( 0%) 0 ( 0%) 0 ( 0%) 745
Typhlitis (inflammation of cecum) CAx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 761
CAx6 1 ( 0%) 0 ( 0%) 0 ( 0%) 741
Tx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 761
Tx6 0 ( 0%) 0 ( 0%) 0 ( 0%) 745
Vomiting CAx4 21 ( 3%) 0 ( 0%) 0 ( 0%) 761
CAx6 19 ( 3%) 0 ( 0%) 0 ( 0%) 741
Tx4 3 ( 0%) 1 ( 0%) 0 ( 0%) 761
Tx6 2 ( 0%) 0 ( 0%) 0 ( 0%) 745
Hemorrhage
Hemorrhage-Other CAx4 1 ( 0%) 0 ( 0%) 0 ( 0%) 761
CAx6 0 ( 0%) 0 ( 0%) 0 ( 0%) 741
Tx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 761
Tx6 0 ( 0%) 0 ( 0%) 0 ( 0%) 745
Melena/GI bleeding CAx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 761
CAx6 1 ( 0%) 0 ( 0%) 0 ( 0%) 741
Tx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 761
Tx6 0 ( 0%) 0 ( 0%) 0 ( 0%) 745
June 2008 Breast Committee CALGB 40101
Breast - 9
Grade of Adverse Event
Arm 3-Severe 4-LifeThr 5-Lethal Total
n (%) n (%) n (%)
Rectal bleeding/hematochezia CAx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 761
CAx6 1 ( 0%) 0 ( 0%) 0 ( 0%) 741
Tx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 761
Tx6 0 ( 0%) 0 ( 0%) 0 ( 0%) 745
Vaginal bleeding CAx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 761
CAx6 0 ( 0%) 0 ( 0%) 0 ( 0%) 741
Tx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 761
Tx6 0 ( 0%) 1 ( 0%) 0 ( 0%) 745
Hepatic
Alkaline phosphatase CAx4 1 ( 0%) 0 ( 0%) 0 ( 0%) 761
CAx6 1 ( 0%) 0 ( 0%) 0 ( 0%) 741
Tx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 761
Tx6 0 ( 0%) 0 ( 0%) 0 ( 0%) 745
Bilirubin CAx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 761
CAx6 0 ( 0%) 0 ( 0%) 0 ( 0%) 741
Tx4 1 ( 0%) 0 ( 0%) 0 ( 0%) 761
Tx6 0 ( 0%) 0 ( 0%) 0 ( 0%) 745
GGT (gamma-Glutamyl
transpeptidase)
CAx4 1 ( 0%) 0 ( 0%) 0 ( 0%) 761
CAx6 0 ( 0%) 0 ( 0%) 0 ( 0%) 741
Tx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 761
Tx6 0 ( 0%) 0 ( 0%) 0 ( 0%) 745
Hepatic-Other CAx4 1 ( 0%) 0 ( 0%) 0 ( 0%) 761
CAx6 0 ( 0%) 0 ( 0%) 0 ( 0%) 741
Tx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 761
Tx6 0 ( 0%) 0 ( 0%) 0 ( 0%) 745
Infection
Infection (documented clinically or
microbial)
CAx4 2 ( 0%) 0 ( 0%) 0 ( 0%) 761
CAx6 2 ( 0%) 0 ( 0%) 0 ( 0%) 741
Tx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 761
Tx6 0 ( 0%) 0 ( 0%) 0 ( 0%) 745
Infection with normal ANC or Grade 1
or 2 neutropenia
CAx4 1 ( 0%) 0 ( 0%) 0 ( 0%) 761
CAx6 0 ( 0%) 0 ( 0%) 0 ( 0%) 741
Tx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 761
Tx6 0 ( 0%) 0 ( 0%) 0 ( 0%) 745
Infection with unknown ANC CAx4 1 ( 0%) 0 ( 0%) 0 ( 0%) 761
CAx6 2 ( 0%) 0 ( 0%) 0 ( 0%) 741
Tx4 2 ( 0%) 0 ( 0%) 0 ( 0%) 761
Tx6 1 ( 0%) 0 ( 0%) 0 ( 0%) 745
June 2008 Breast Committee CALGB 40101
Breast - 10
Grade of Adverse Event
Arm 3-Severe 4-LifeThr 5-Lethal Total
n (%) n (%) n (%)
Infection/Febrile
Febrile neutropenia (fever of unknown
origin)
CAx4 35 ( 5%) 4 ( 1%) 0 ( 0%) 761
CAx6 46 ( 6%) 3 ( 0%) 0 ( 0%) 741
Tx4 2 ( 0%) 0 ( 0%) 0 ( 0%) 761
Tx6 0 ( 0%) 0 ( 0%) 0 ( 0%) 745
Infection (documented clinically or
microbial)
CAx4 8 ( 1%) 0 ( 0%) 0 ( 0%) 761
CAx6 16 ( 2%) 0 ( 0%) 0 ( 0%) 741
Infection with unknown ANC CAx4 1 ( 0%) 0 ( 0%) 0 ( 0%) 761
CAx6 1 ( 0%) 0 ( 0%) 0 ( 0%) 741
Tx6 1 ( 0%) 0 ( 0%) 0 ( 0%) 745
Infection without neutropenia CAx4 7 ( 1%) 0 ( 0%) 0 ( 0%) 761
CAx6 9 ( 1%) 0 ( 0%) 0 ( 0%) 741
Tx4 4 ( 1%) 0 ( 0%) 0 ( 0%) 761
Tx6 3 ( 0%) 0 ( 0%) 0 ( 0%) 745
Infection/Febrile Neutropenia-Other CAx4 1 ( 0%) 0 ( 0%) 0 ( 0%) 761
CAx6 0 ( 0%) 0 ( 0%) 0 ( 0%) 741
Tx4 1 ( 0%) 0 ( 0%) 0 ( 0%) 761
Tx6 0 ( 0%) 0 ( 0%) 0 ( 0%) 745
Metabolic/Laborato
ALT, SGPT (serum glutamic pyruvic
transaminase)
CAx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 761
CAx6 1 ( 0%) 0 ( 0%) 0 ( 0%) 741
Tx4 6 ( 1%) 0 ( 0%) 0 ( 0%) 761
Tx6 6 ( 1%) 0 ( 0%) 0 ( 0%) 745
AST, SGOT(serum glutamic
oxaloacetic transaminase)
CAx4 1 ( 0%) 0 ( 0%) 0 ( 0%) 761
CAx6 1 ( 0%) 0 ( 0%) 0 ( 0%) 741
Tx4 1 ( 0%) 0 ( 0%) 0 ( 0%) 761
Tx6 1 ( 0%) 0 ( 0%) 0 ( 0%) 745
Albumin, serum-low
(hypoalbuminemia)
CAx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 761
CAx6 1 ( 0%) 0 ( 0%) 0 ( 0%) 741
Tx4 1 ( 0%) 0 ( 0%) 0 ( 0%) 761
Tx6 0 ( 0%) 0 ( 0%) 0 ( 0%) 745
Creatinine CAx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 761
CAx6 1 ( 0%) 0 ( 0%) 0 ( 0%) 741
Tx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 761
Tx6 0 ( 0%) 0 ( 0%) 0 ( 0%) 745
Glucose serum-high (hyperglycemia) CAx4 3 ( 0%) 0 ( 0%) 0 ( 0%) 761
CAx6 4 ( 1%) 1 ( 0%) 0 ( 0%) 741
June 2008 Breast Committee CALGB 40101
Breast - 11
Grade of Adverse Event
Arm 3-Severe 4-LifeThr 5-Lethal Total
n (%) n (%) n (%)
Tx4 11 ( 1%) 0 ( 0%) 0 ( 0%) 761
Tx6 19 ( 3%) 1 ( 0%) 0 ( 0%) 745
Hyperkalemia CAx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 761
CAx6 0 ( 0%) 0 ( 0%) 0 ( 0%) 741
Tx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 761
Tx6 1 ( 0%) 0 ( 0%) 0 ( 0%) 745
Hypokalemia CAx4 7 ( 1%) 0 ( 0%) 0 ( 0%) 761
CAx6 5 ( 1%) 0 ( 0%) 0 ( 0%) 741
Tx4 4 ( 1%) 0 ( 0%) 0 ( 0%) 761
Tx6 1 ( 0%) 0 ( 0%) 0 ( 0%) 745
Hyponatremia CAx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 761
CAx6 0 ( 0%) 0 ( 0%) 0 ( 0%) 741
Tx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 761
Tx6 1 ( 0%) 1 ( 0%) 0 ( 0%) 745
Lipase CAx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 761
CAx6 1 ( 0%) 0 ( 0%) 0 ( 0%) 741
Tx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 761
Tx6 0 ( 0%) 0 ( 0%) 0 ( 0%) 745
Musculoskeletal/Soft tissue
Muscle weakness, generalized or
specific area
CAx4 2 ( 0%) 0 ( 0%) 0 ( 0%) 761
CAx6 0 ( 0%) 1 ( 0%) 0 ( 0%) 741
Tx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 761
Tx6 0 ( 0%) 0 ( 0%) 0 ( 0%) 745
Myositis (inflammation/damage of
muscle)
CAx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 761
CAx6 0 ( 0%) 0 ( 0%) 0 ( 0%) 741
Tx4 1 ( 0%) 0 ( 0%) 0 ( 0%) 761
Tx6 0 ( 0%) 0 ( 0%) 0 ( 0%) 745
Neurology
Arachnoiditis/meningismus/radiculitis CAx4 1 ( 0%) 0 ( 0%) 0 ( 0%) 761
CAx6 0 ( 0%) 0 ( 0%) 0 ( 0%) 741
Tx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 761
Tx6 0 ( 0%) 0 ( 0%) 0 ( 0%) 745
Ataxia (incoordination) CAx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 761
CAx6 0 ( 0%) 0 ( 0%) 0 ( 0%) 741
Tx4 1 ( 0%) 0 ( 0%) 0 ( 0%) 761
Tx6 0 ( 0%) 0 ( 0%) 0 ( 0%) 745
Dizziness CAx4 1 ( 0%) 0 ( 0%) 0 ( 0%) 761
CAx6 1 ( 0%) 0 ( 0%) 0 ( 0%) 741
Tx4 1 ( 0%) 0 ( 0%) 0 ( 0%) 761
June 2008 Breast Committee CALGB 40101
Breast - 12
Grade of Adverse Event
Arm 3-Severe 4-LifeThr 5-Lethal Total
n (%) n (%) n (%)
Tx6 0 ( 0%) 0 ( 0%) 0 ( 0%) 745
Mood alteration CAx4 2 ( 0%) 1 ( 0%) 0 ( 0%) 761
CAx6 0 ( 0%) 0 ( 0%) 0 ( 0%) 741
Tx4 2 ( 0%) 0 ( 0%) 0 ( 0%) 761
Tx6 3 ( 0%) 0 ( 0%) 0 ( 0%) 745
Neuropathy: motor CAx4 1 ( 0%) 0 ( 0%) 0 ( 0%) 761
CAx6 1 ( 0%) 0 ( 0%) 0 ( 0%) 741
Tx4 14 ( 2%) 1 ( 0%) 0 ( 0%) 761
Tx6 23 ( 3%) 0 ( 0%) 0 ( 0%) 745
Neuropathy: sensory CAx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 761
CAx6 1 ( 0%) 0 ( 0%) 0 ( 0%) 741
Tx4 33 ( 4%) 0 ( 0%) 0 ( 0%) 761
Tx6 73 ( 10%) 1 ( 0%) 0 ( 0%) 745
Syncope (fainting) CAx4 1 ( 0%) 0 ( 0%) 0 ( 0%) 761
CAx6 2 ( 0%) 0 ( 0%) 0 ( 0%) 741
Tx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 761
Tx6 6 ( 1%) 0 ( 0%) 0 ( 0%) 745
Ocular/Visual
Ocular/Visual-Other CAx4 1 ( 0%) 0 ( 0%) 0 ( 0%) 761
CAx6 0 ( 0%) 0 ( 0%) 0 ( 0%) 741
Tx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 761
Tx6 0 ( 0%) 0 ( 0%) 0 ( 0%) 745
Vision-photophobia CAx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 761
CAx6 1 ( 0%) 0 ( 0%) 0 ( 0%) 741
Tx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 761
Tx6 0 ( 0%) 0 ( 0%) 0 ( 0%) 745
Watery eye (epiphora tearing) CAx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 761
CAx6 1 ( 0%) 0 ( 0%) 0 ( 0%) 741
Tx4 1 ( 0%) 0 ( 0%) 0 ( 0%) 761
Tx6 0 ( 0%) 0 ( 0%) 0 ( 0%) 745
Pain
Arthralgia (joint pain) CAx4 2 ( 0%) 0 ( 0%) 0 ( 0%) 761
CAx6 3 ( 0%) 0 ( 0%) 0 ( 0%) 741
Tx4 15 ( 2%) 0 ( 0%) 0 ( 0%) 761
Tx6 18 ( 2%) 2 ( 0%) 0 ( 0%) 745
Headache CAx4 5 ( 1%) 0 ( 0%) 0 ( 0%) 761
CAx6 7 ( 1%) 1 ( 0%) 0 ( 0%) 741
Tx4 1 ( 0%) 0 ( 0%) 0 ( 0%) 761
Tx6 0 ( 0%) 1 ( 0%) 0 ( 0%) 745
Neuropathic pain (e.g. jaw pain ) CAx4 1 ( 0%) 0 ( 0%) 0 ( 0%) 761
June 2008 Breast Committee CALGB 40101
Breast - 13
Grade of Adverse Event
Arm 3-Severe 4-LifeThr 5-Lethal Total
n (%) n (%) n (%)
CAx6 0 ( 0%) 0 ( 0%) 0 ( 0%) 741
Tx4 1 ( 0%) 1 ( 0%) 0 ( 0%) 761
Tx6 3 ( 0%) 0 ( 0%) 0 ( 0%) 745
Pain CAx4 9 ( 1%) 0 ( 0%) 0 ( 0%) 761
CAx6 10 ( 1%) 0 ( 0%) 0 ( 0%) 741
Tx4 36 ( 5%) 1 ( 0%) 0 ( 0%) 761
Tx6 40 ( 5%) 3 ( 0%) 0 ( 0%) 745
Pain - Other CAx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 761
CAx6 2 ( 0%) 0 ( 0%) 0 ( 0%) 741
Tx4 1 ( 0%) 0 ( 0%) 0 ( 0%) 761
Tx6 3 ( 0%) 0 ( 0%) 0 ( 0%) 745
Pulmonary
Adult respiratory distress syndrome
(ARDS)
CAx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 761
CAx6 0 ( 0%) 1 ( 0%) 0 ( 0%) 741
Tx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 761
Tx6 0 ( 0%) 0 ( 0%) 0 ( 0%) 745
Dyspnea (shortness of breath) CAx4 3 ( 0%) 0 ( 0%) 0 ( 0%) 761
CAx6 7 ( 1%) 1 ( 0%) 0 ( 0%) 741
Tx4 3 ( 0%) 0 ( 0%) 0 ( 0%) 761
Tx6 3 ( 0%) 1 ( 0%) 0 ( 0%) 745
Pneumonitis/pulmonary infiltrates CAx4 1 ( 0%) 0 ( 0%) 0 ( 0%) 761
CAx6 3 ( 0%) 2 ( 0%) 0 ( 0%) 741
Tx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 761
Tx6 0 ( 0%) 0 ( 0%) 0 ( 0%) 745
Pulmonary-Other CAx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 761
CAx6 1 ( 0%) 0 ( 0%) 0 ( 0%) 741
Tx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 761
Tx6 0 ( 0%) 0 ( 0%) 0 ( 0%) 745
Pulmonary/Upper Respiratory
Hypoxia CAx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 761
CAx6 1 ( 0%) 0 ( 0%) 0 ( 0%) 741
Tx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 761
Tx6 1 ( 0%) 0 ( 0%) 0 ( 0%) 745
Renal/Genitourinar
Dysuria (painful urination) CAx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 761
CAx6 1 ( 0%) 0 ( 0%) 0 ( 0%) 741
Tx4 1 ( 0%) 0 ( 0%) 0 ( 0%) 761
Tx6 0 ( 0%) 0 ( 0%) 0 ( 0%) 745
Incontinence CAx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 761
CAx6 1 ( 0%) 0 ( 0%) 0 ( 0%) 741
June 2008 Breast Committee CALGB 40101
Breast - 14
Grade of Adverse Event
Arm 3-Severe 4-LifeThr 5-Lethal Total
n (%) n (%) n (%)
Tx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 761
Tx6 0 ( 0%) 0 ( 0%) 0 ( 0%) 745
Renal/Genitourinary - Other CAx4 1 ( 0%) 0 ( 0%) 0 ( 0%) 761
CAx6 0 ( 0%) 0 ( 0%) 0 ( 0%) 741
Tx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 761
Tx6 0 ( 0%) 0 ( 0%) 0 ( 0%) 745
Urinary frequency/urgency CAx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 761
CAx6 1 ( 0%) 0 ( 0%) 0 ( 0%) 741
Tx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 761
Tx6 0 ( 0%) 0 ( 0%) 0 ( 0%) 745
Sexual/Reproductiv
Irregular menses (change from
baseline)
CAx4 4 ( 1%) 0 ( 0%) 0 ( 0%) 761
CAx6 4 ( 1%) 0 ( 0%) 0 ( 0%) 741
Tx4 3 ( 0%) 0 ( 0%) 0 ( 0%) 761
Tx6 3 ( 0%) 0 ( 0%) 0 ( 0%) 745
Sexual/Reproductive Function - Other CAx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 761
CAx6 0 ( 0%) 0 ( 0%) 0 ( 0%) 741
Tx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 761
Tx6 1 ( 0%) 0 ( 0%) 0 ( 0%) 745
Vascular
Acute vascular leak syndrome CAx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 761
CAx6 0 ( 0%) 0 ( 0%) 0 ( 0%) 741
Tx4 1 ( 0%) 0 ( 0%) 0 ( 0%) 761
Tx6 0 ( 0%) 0 ( 0%) 0 ( 0%) 745
Thrombosis/embolism (vascular
access-related)
CAx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 761
CAx6 0 ( 0%) 0 ( 0%) 0 ( 0%) 741
Tx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 761
Tx6 1 ( 0%) 0 ( 0%) 0 ( 0%) 745
Thrombosis/thrombus/embolism CAx4 4 ( 1%) 1 ( 0%) 0 ( 0%) 761
CAx6 0 ( 0%) 5 ( 1%) 0 ( 0%) 741
Tx4 0 ( 0%) 1 ( 0%) 0 ( 0%) 761
Tx6 1 ( 0%) 0 ( 0%) 0 ( 0%) 745
SUMMARY
Maximum Non-Hematologic AE CAx4 122 ( 16%) 8 ( 1%) 1 ( 0%) 761
CAx6 173 ( 23%) 18 ( 2%) 1 ( 0%) 741
Tx4 136 ( 18%) 5 ( 1%) 0 ( 0%) 761
Tx6 175 ( 23%) 10 ( 1%) 0 ( 0%) 745
SUMMARY
Maximum Overall AE CAx4 145 ( 19%) 137 ( 18%) 1 ( 0%) 761
June 2008 Breast Committee CALGB 40101
Breast - 15
Grade of Adverse Event
Arm 3-Severe 4-LifeThr 5-Lethal Total
n (%) n (%) n (%)
CAx6 173 ( 23%) 192 ( 26%) 1 ( 0%) 741
Tx4 150 ( 20%) 12 ( 2%) 0 ( 0%) 761
Tx6 186 ( 25%) 15 ( 2%) 0 ( 0%) 745
B. Adverse Events after Completing Protocol Therapy:
2837 patients have follow-up data which reported long-term or delayed toxicity after the completion of protocol
therapy.
One hundred twelve (112) of these 2837 patients reported adverse events of Grade 3 or higher severity during post-
treatment follow-up.
Four patients died of treatment-related causes (AML/MDS) secondary to protocol CA.
Nineteen patients experienced significant LVEF toxicity during post-treatment follow-up. Eighteen were randomized to
the CA regimens and one to the Tx6 regimen.
Grade of Adverse Event
Arm 3-Severe 4-LifeThr 5-Lethal Total
n (%) n (%) n (%)
ALLERGY/IMMUNOLOGY
Hypersensitivity NOS CAx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 707
CAx6 0 ( 0%) 0 ( 0%) 0 ( 0%) 705
Tx4 1 ( 1%) 0 ( 0%) 0 ( 0%) 728
Tx6 0 ( 0%) 0 ( 0%) 0 ( 0%) 697
BLOOD/BONE MARROW
Haemoglobin CAx4 1 ( 1%) 0 ( 0%) 0 ( 0%) 707
CAx6 0 ( 0%) 1 ( 1%) 0 ( 0%) 705
Tx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 728
Tx6 1 ( 1%) 0 ( 0%) 0 ( 0%) 697
Leukopenia NOS CAx4 1 ( 1%) 1 ( 1%) 0 ( 0%) 707
CAx6 0 ( 0%) 1 ( 1%) 0 ( 0%) 705
Tx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 728
Tx6 0 ( 0%) 0 ( 0%) 0 ( 0%) 697
Neutrophil count CAx4 1 ( 1%) 1 ( 1%) 0 ( 0%) 707
CAx6 0 ( 0%) 1 ( 1%) 0 ( 0%) 705
Tx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 728
Tx6 0 ( 0%) 0 ( 0%) 0 ( 0%) 697
Packed red blood cells CAx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 707
CAx6 1 ( 1%) 0 ( 0%) 0 ( 0%) 705
Tx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 728
Tx6 0 ( 0%) 0 ( 0%) 0 ( 0%) 697
Platelet count decrease CAx4 1 ( 1%) 0 ( 0%) 0 ( 0%) 707
CAx6 0 ( 0%) 0 ( 0%) 0 ( 0%) 705
Tx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 728
Tx6 0 ( 0%) 0 ( 0%) 0 ( 0%) 697
CARDIAC GENERAL
Pulmonary hypertension CAx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 707
June 2008 Breast Committee CALGB 40101
Breast - 16
Grade of Adverse Event
Arm 3-Severe 4-LifeThr 5-Lethal Total
n (%) n (%) n (%)
CAx6 1 ( 1%) 0 ( 0%) 0 ( 0%) 705
Tx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 728
Tx6 0 ( 0%) 0 ( 0%) 0 ( 0%) 697
Restrictive cardiomy CAx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 707
CAx6 0 ( 0%) 1 ( 1%) 0 ( 0%) 705
Tx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 728
Tx6 0 ( 0%) 0 ( 0%) 0 ( 0%) 697
CARDIOVASCULAR
(ARRHYTHMIA)
Palpitations CAx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 707
CAx6 0 ( 0%) 0 ( 0%) 0 ( 0%) 705
Tx4 1 ( 1%) 0 ( 0%) 0 ( 0%) 728
Tx6 0 ( 0%) 0 ( 0%) 0 ( 0%) 697
Sinus bradycardia CAx4 1 ( 1%) 0 ( 0%) 0 ( 0%) 707
CAx6 1 ( 1%) 0 ( 0%) 0 ( 0%) 705
Tx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 728
Tx6 0 ( 0%) 0 ( 0%) 0 ( 0%) 697
Supraventricular
arrhythmia CAx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 707
CAx6 0 ( 0%) 0 ( 0%) 0 ( 0%) 705
Tx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 728
Tx6 1 ( 1%) 0 ( 0%) 0 ( 0%) 697
Ventricular arrhythmia CAx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 707
CAx6 0 ( 0%) 0 ( 0%) 0 ( 0%) 705
Tx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 728
Tx6 0 ( 0%) 1 ( 1%) 0 ( 0%) 697
CARDIOVASCULAR (GENERAL)
Hypertension NOS CAx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 707
CAx6 0 ( 0%) 0 ( 0%) 0 ( 0%) 705
Tx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 728
Tx6 1 ( 1%) 0 ( 0%) 0 ( 0%) 697
Left ventricular failure CAx4 3 ( 1%) 0 ( 0%) 0 ( 0%) 707
CAx6 13 ( 2%) 2 ( 1%) 0 ( 0%) 705
Tx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 728
Tx6 0 ( 0%) 1 ( 1%) 0 ( 0%) 697
Myocardial ischaemia CAx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 707
CAx6 0 ( 0%) 1 ( 1%) 0 ( 0%) 705
Tx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 728
Tx6 0 ( 0%) 0 ( 0%) 0 ( 0%) 697
Thrombosis CAx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 707
CAx6 0 ( 0%) 2 ( 1%) 0 ( 0%) 705
Tx4 1 ( 1%) 0 ( 0%) 0 ( 0%) 728
Tx6 3 ( 1%) 0 ( 0%) 0 ( 0%) 697
Other CAx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 707
CAx6 1 ( 1%) 0 ( 0%) 0 ( 0%) 705
Tx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 728
Tx6 0 ( 0%) 0 ( 0%) 0 ( 0%) 697
CONSTITUTIONAL SYMPTOMS
Fatigue CAx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 707
June 2008 Breast Committee CALGB 40101
Breast - 17
Grade of Adverse Event
Arm 3-Severe 4-LifeThr 5-Lethal Total
n (%) n (%) n (%)
CAx6 3 ( 1%) 0 ( 0%) 0 ( 0%) 705
Tx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 728
Tx6 0 ( 0%) 0 ( 0%) 0 ( 0%) 697
DERMATOLOGY/SKIN
Culture wound positive CAx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 707
CAx6 1 ( 1%) 0 ( 0%) 0 ( 0%) 705
Tx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 728
Tx6 0 ( 0%) 0 ( 0%) 0 ( 0%) 697
ENDOCRINE
Hot flushes NOS CAx4 2 ( 1%) 0 ( 0%) 0 ( 0%) 707
CAx6 0 ( 0%) 0 ( 0%) 0 ( 0%) 705
Tx4 1 ( 1%) 0 ( 0%) 0 ( 0%) 728
Tx6 2 ( 1%) 0 ( 0%) 0 ( 0%) 697
Virilism CAx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 707
CAx6 1 ( 1%) 0 ( 0%) 0 ( 0%) 705
Tx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 728
Tx6 0 ( 0%) 0 ( 0%) 0 ( 0%) 697
GASTROINTESTINAL
Dehydration CAx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 707
CAx6 0 ( 0%) 1 ( 1%) 0 ( 0%) 705
Tx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 728
Tx6 0 ( 0%) 0 ( 0%) 0 ( 0%) 697
Diarrhoea NOS CAx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 707
CAx6 0 ( 0%) 0 ( 0%) 0 ( 0%) 705
Tx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 728
Tx6 1 ( 1%) 0 ( 0%) 0 ( 0%) 697
Nausea CAx4 1 ( 1%) 0 ( 0%) 0 ( 0%) 707
CAx6 0 ( 0%) 0 ( 0%) 0 ( 0%) 705
Tx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 728
Tx6 0 ( 0%) 0 ( 0%) 0 ( 0%) 697
Vomiting NOS CAx4 1 ( 1%) 0 ( 0%) 0 ( 0%) 707
CAx6 0 ( 0%) 0 ( 0%) 0 ( 0%) 705
Tx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 728
Tx6 0 ( 0%) 0 ( 0%) 0 ( 0%) 697
HEPATIC
Alanine aminotransfer. CAx4 0 ( 0%) 1 ( 1%) 0 ( 0%) 707
CAx6 0 ( 0%) 0 ( 0%) 0 ( 0%) 705
Tx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 728
Tx6 1 ( 1%) 0 ( 0%) 0 ( 0%) 697
Aspartate aminotrans. CAx4 0 ( 0%) 1 ( 1%) 0 ( 0%) 707
CAx6 0 ( 0%) 0 ( 0%) 0 ( 0%) 705
Tx4 2 ( 1%) 0 ( 0%) 0 ( 0%) 728
Tx6 0 ( 0%) 0 ( 0%) 0 ( 0%) 697
Gamma-glutamyltransf CAx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 707
CAx6 0 ( 0%) 0 ( 0%) 0 ( 0%) 705
Tx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 728
Tx6 1 ( 1%) 0 ( 0%) 0 ( 0%) 697
INFECTION
June 2008 Breast Committee CALGB 40101
Breast - 18
Grade of Adverse Event
Arm 3-Severe 4-LifeThr 5-Lethal Total
n (%) n (%) n (%)
Febrile neutropenia CAx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 707
CAx6 1 ( 1%) 1 ( 1%) 0 ( 0%) 705
Tx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 728
Tx6 0 ( 0%) 0 ( 0%) 0 ( 0%) 697
INFECTION/FEBRILE NEUTRO.
Infection NOS CAx4 1 ( 1%) 0 ( 0%) 0 ( 0%) 707
CAx6 1 ( 1%) 0 ( 0%) 0 ( 0%) 705
Tx4 1 ( 1%) 0 ( 0%) 0 ( 0%) 728
Tx6 2 ( 1%) 0 ( 0%) 0 ( 0%) 697
LYMPHATICS
Lymphangiopathy NOS CAx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 707
CAx6 2 ( 1%) 0 ( 0%) 0 ( 0%) 705
Tx4 1 ( 1%) 0 ( 0%) 0 ( 0%) 728
Tx6 0 ( 0%) 0 ( 0%) 0 ( 0%) 697
MUSCULOSKELETAL/SOFT
Other CAx4 1 ( 1%) 0 ( 0%) 0 ( 0%) 707
CAx6 0 ( 0%) 0 ( 0%) 0 ( 0%) 705
Tx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 728
Tx6 0 ( 0%) 0 ( 0%) 0 ( 0%) 697
NEUROLOGY
Anxiety CAx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 707
CAx6 0 ( 0%) 0 ( 0%) 0 ( 0%) 705
Tx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 728
Tx6 1 ( 1%) 0 ( 0%) 0 ( 0%) 697
Cerebral ischaemia CAx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 707
CAx6 0 ( 0%) 1 ( 1%) 0 ( 0%) 705
Tx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 728
Tx6 0 ( 0%) 0 ( 0%) 0 ( 0%) 697
Extrapyramidal disorder CAx4 1 ( 1%) 0 ( 0%) 0 ( 0%) 707
CAx6 0 ( 0%) 0 ( 0%) 0 ( 0%) 705
Tx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 728
Tx6 0 ( 0%) 0 ( 0%) 0 ( 0%) 697
Insomnia CAx4 1 ( 1%) 0 ( 0%) 0 ( 0%) 707
CAx6 0 ( 0%) 0 ( 0%) 0 ( 0%) 705
Tx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 728
Tx6 0 ( 0%) 0 ( 0%) 0 ( 0%) 697
Memory impairment CAx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 707
CAx6 1 ( 1%) 0 ( 0%) 0 ( 0%) 705
Tx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 728
Tx6 0 ( 0%) 0 ( 0%) 0 ( 0%) 697
Peripheral motor
neuropathy CAx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 707
CAx6 0 ( 0%) 0 ( 0%) 0 ( 0%) 705
Tx4 4 ( 1%) 0 ( 0%) 0 ( 0%) 728
Tx6 1 ( 1%) 0 ( 0%) 0 ( 0%) 697
Peripheral sensory
neuropathy CAx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 707
CAx6 1 ( 1%) 0 ( 0%) 0 ( 0%) 705
Tx4 5 ( 1%) 0 ( 0%) 0 ( 0%) 728
June 2008 Breast Committee CALGB 40101
Breast - 19
Grade of Adverse Event
Arm 3-Severe 4-LifeThr 5-Lethal Total
n (%) n (%) n (%)
Tx6 7 ( 2%) 0 ( 0%) 0 ( 0%) 697
Syncope CAx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 707
CAx6 0 ( 0%) 0 ( 0%) 0 ( 0%) 705
Tx4 1 ( 1%) 0 ( 0%) 0 ( 0%) 728
Tx6 0 ( 0%) 0 ( 0%) 0 ( 0%) 697
OCULAR/VISUAL
Cataract CAx4 1 ( 1%) 0 ( 0%) 0 ( 0%) 707
CAx6 0 ( 0%) 0 ( 0%) 0 ( 0%) 705
Tx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 728
Tx6 1 ( 1%) 0 ( 0%) 0 ( 0%) 697
PAIN
Abdominal pain NOS CAx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 707
CAx6 0 ( 0%) 0 ( 0%) 0 ( 0%) 705
Tx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 728
Tx6 1 ( 1%) 0 ( 0%) 0 ( 0%) 697
Arthralgia CAx4 1 ( 1%) 0 ( 0%) 0 ( 0%) 707
CAx6 1 ( 1%) 0 ( 0%) 0 ( 0%) 705
Tx4 3 ( 1%) 0 ( 0%) 0 ( 0%) 728
Tx6 4 ( 1%) 0 ( 0%) 0 ( 0%) 697
Bone pain CAx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 707
CAx6 0 ( 0%) 0 ( 0%) 0 ( 0%) 705
Tx4 1 ( 1%) 0 ( 0%) 0 ( 0%) 728
Tx6 0 ( 0%) 0 ( 0%) 0 ( 0%) 697
Chest pain CAx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 707
CAx6 1 ( 1%) 0 ( 0%) 0 ( 0%) 705
Tx4 1 ( 1%) 0 ( 0%) 0 ( 0%) 728
Tx6 0 ( 0%) 0 ( 0%) 0 ( 0%) 697
Headache CAx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 707
CAx6 0 ( 0%) 0 ( 0%) 0 ( 0%) 705
Tx4 1 ( 1%) 0 ( 0%) 0 ( 0%) 728
Tx6 0 ( 0%) 0 ( 0%) 0 ( 0%) 697
Headache NOS CAx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 707
CAx6 0 ( 0%) 0 ( 0%) 0 ( 0%) 705
Tx4 1 ( 1%) 0 ( 0%) 0 ( 0%) 728
Tx6 0 ( 0%) 0 ( 0%) 0 ( 0%) 697
Myalgia CAx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 707
CAx6 1 ( 1%) 0 ( 0%) 0 ( 0%) 705
Tx4 1 ( 1%) 0 ( 0%) 0 ( 0%) 728
Tx6 2 ( 1%) 0 ( 0%) 0 ( 0%) 697
Neuralgia NOS CAx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 707
CAx6 0 ( 0%) 0 ( 0%) 0 ( 0%) 705
Tx4 1 ( 1%) 0 ( 0%) 0 ( 0%) 728
Tx6 0 ( 0%) 0 ( 0%) 0 ( 0%) 697
PULMONARY
Dyspnoea NOS CAx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 707
CAx6 1 ( 1%) 0 ( 0%) 0 ( 0%) 705
Tx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 728
Tx6 0 ( 0%) 0 ( 0%) 0 ( 0%) 697
June 2008 Breast Committee CALGB 40101
Breast - 20
Grade of Adverse Event
Arm 3-Severe 4-LifeThr 5-Lethal Total
n (%) n (%) n (%)
Pulmonary fibrosis CAx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 707
CAx6 0 ( 0%) 0 ( 0%) 0 ( 0%) 705
Tx4 0 ( 0%) 1 ( 1%) 0 ( 0%) 728
Tx6 0 ( 0%) 0 ( 0%) 0 ( 0%) 697
Other CAx4 1 ( 1%) 0 ( 0%) 0 ( 0%) 707
CAx6 0 ( 0%) 0 ( 0%) 0 ( 0%) 705
Tx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 728
Tx6 0 ( 0%) 0 ( 0%) 0 ( 0%) 697
RENAL/GENITOURINARY
Other CAx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 707
CAx6 0 ( 0%) 0 ( 0%) 0 ( 0%) 705
Tx4 1 ( 1%) 0 ( 0%) 0 ( 0%) 728
Tx6 0 ( 0%) 0 ( 0%) 0 ( 0%) 697
SECONDARY MALIGNANCY
Secondary to cancer rx CAx4 0 ( 0%) 0 ( 0%) 1 ( 1%) 707
CAx6 0 ( 0%) 0 ( 0%) 3 ( 1%) 705
Tx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 728
Tx6 0 ( 0%) 0 ( 0%) 0 ( 0%) 697
SEXUAL/REPRODUCTIVE
Menstrual irregularity CAx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 707
CAx6 1 ( 1%) 0 ( 0%) 0 ( 0%) 705
Tx4 0 ( 0%) 0 ( 0%) 0 ( 0%) 728
Tx6 0 ( 0%) 0 ( 0%) 0 ( 0%) 697
SUMMARY
Maximum Overall AE CAx4 12 ( 2%) 4 ( 1%) 1 ( 0%) 707
CAx6 29 ( 4%) 8 ( 1%) 3 ( 0%) 705
Tx4 25 ( 3%) 2 ( 0%) 0 ( 0%) 728
Tx6 26 ( 4%) 2 ( 0%) 0 ( 0%) 697
