Transcript TnI

A Multidisciplinary Approach to
Successful Management of
Cardiovascular Disease in the
Cancer Patient
The India Association Cultural & Educational Center
Saturday, January 22, 2011
Ocala, Florida
Program Moderator
Rama Balaraman, MD
Medical Oncologist/Hematologist
Ocala Oncology
Ocala, Florida
Dr. Balaraman’s Disclosures
Advisory Board
• PNH-Alexion Pharmaceuticals
• Genentech
Commercial Supporter
This certified CME activity is supported by an education
grant from
• Pfizer
Learning Objectives
At the end of this program you should be able to:
• Explain the etiology and epidemiology of short and longterm cardiovascular effects of anti-cancer treatments.
• Detail the evidence-based guidelines that provide
recommended evaluation/assessment of risk and/or
management of short and long-term cardiovascular
effects of anticancer treatments using evidence-based
methods.
Learning Objectives (cont)
• Describe the therapeutic goals for management of
short and long-term cardiovascular effects of
anticancer treatments.
• Incorporate into practice, assessment and
management recommendations so that communitybased oncologists, cardiologists, internal medicine
and family practitioners can provide optimal
multidisciplinary care to cancer patients and
survivors with short and long-term cardiovascular
effects of anticancer treatments.
Accreditation
• Oncology TodayTM and The University of Texas
Medical Branch at Galveston are pleased to provide
CME credit
• In order to receive credit, please complete the
Attendance Record/Evaluation found in your
program folder and leave it at the registration desk
Successful Management of Cardiovascular
Disease in the Cancer Patient: A Focus on
Hypertension and Cardiomyopathy
Discussion and Case Studies
JEAN-BERNARD DURAND, M.D., FCCP, FACC
ASSOCIATE PROFESSOR OF MEDICINE
MEDICAL DIRECTOR CARDIOMYOPATHY SERVICES
UNIVERSITY OF TEXAS
M. D. ANDERSON CANCER CENTER
HOUSTON, TEXAS
Jean-Bernard Durand, M.D. Disclosures
• I will not discuss off label use and/or investigational
use in my presentation.
• I have the following financial relationships to disclose:
– DSMB- Steba Biotech
• Employee of: University of Texas M. D. Anderson
Cancer Center
Overview
• No standard of care exist evaluation of Patients
prior to being enrolled in tyrosine Kinase
inhibitors protocols
• Cardiovascular disease is the number two Killer
of cancer survivors
• 108 Million Baby Boomers will enter Healthcare
Industry by 2015
• By 2015 Over 15 Million U.S. Cancer Survivors
– Many definitions of cancer survivor:
Cardiologist viewpoint, survivor starts at time
of diagnosis (Dr. Fitzhugh)
Tyrosine Kinases
Growth Factors
src, , fgr, yes
lyn, syn, slk, fps,
abl, rel,
(PDGF-),PDGF-B, GDVEGF FGFs, (acidic, basic
hst,int-2,
FGF5
FGF6, KGF)
TGF (1-8), activin, BMPs,
MIS,
IGF-I, IGF-II
EGF,TGFa,
JE KC
GTP
GDP
Effectors
PLA2,
PLC,crk Kinases
Protein
raf/mil, l(1)polehole,
mos
Messenger
s
Ca
Nuclear Proteins
c,L,N,B myc
fos, fosB, fra-1,-2
jun (AP1), junB,
junD
myb
erbA
ski
PKC
Coupling
Proteins
H, K, N, R ras
rho, ral, rev,
ypt, rap, bcl2
Intracellul
ar
Receptors
EGF-R (erb), neu,
erbB-2,
PDGF-Rs (A, B), kit,
fms IGF-R, ros,
met
FGFR, flg, trk
Cardiac
Signaling
Pathways
Ca MK
TF
determination genes (myoD,myogenin,
myf-5, MRF4; ld)
homeotic genes (Xhox,3)
“zinc finger” transcription factors (EGR1)
B-ZIP transcription factors
(CREB)
anti-oncogenes
(rb, p53, s-myc)
Heart Failure Classifications
ACC/AHA Guidelines for the Evaluation and the
Management of Chronic Heart Failure in the Adult
ACE Inhibitor Therapy
A
Stage
High risk for developing
heart failure (HF)
B
Asymptomatic HF
C
Symptomatic HF
D
Refractory end-stage HF
Guideline Recommendation
ACE inhibition in patients with history of
atherosclerotic vascular disease, diabetes
mellitus, or hypertension and associated risk
factors
ACE inhibition in patients with recent or
remote history of myocardial infarction
regardless of ejection fraction
ACE inhibition in patients with reduced
ejection fraction, whether or not they have
experienced a myocardial infarction
ACE inhibition in all patients, unless
contraindicated
Includes all the above listed
Hunt SA et al. J Am Coll Cardiol. 2001; 38:2101–2113.
ACC/AHA Guidelines for the Evaluation and
Management of Chronic Heart Failure in the Adult
-Blockade Therapy
Stage
Patient Description
A
High risk for developing
heart failure (HF)
For patients that are on combination therapy for
hypertension (HTN), drugs that treat HTN and HF (eg,
diuretics, ACE inhibitors, and
-blockers) are preferred
B
Asymptomatic HF
Patients with a recent myocardial infarction, regardless
of ejection fraction
Patients with a reduced ejection fraction, whether or not
they have experienced a myocardial infarction
C
Symptomatic HF
In all stable patients, unless contraindicated. Patients
should have no or minimal evidence of fluid retention
and should not have required treatment recently with a
intravenous positive inotropic agent
D
Refractory end-stage HF
Includes all the above listed
Hunt SA et al. J Am Coll Cardiol. 2001; 38:2101–2113.
Beta Blockers Proven Effective
in Preventing and Treating CHF
Examples:
• Carvedilol (Coreg®)
• Metoprolol (Toprol XL®)
LET’S VOTE!
Question # 1
• 56 y/o patient with breast cancer Her-2-Neu
positive. No h/o DM. Present for treatment
with Trastuzumab
• BP on presentation to clinic was 168/92.
What is your treatment of choice for HTN?
A) Start Beta Blocker
B) Start Ace-Inhibitor or ARB
C) Neither, start Trastuzumab immediately
D) A and B
Cardiotoxicity
 One of the major factors limiting
the use of chemotherapy
 Acute or Subacute
within 2 weeks
 Chronic (more frequent);
 Early Onset
within 1 year
 Late Onset
> 1 year
 dose dependent
 dilated/hypokinetic cardiomyopathy
 poor prognosis
DEFINITION OF CARDIOTOXICITY
- Oncology Guidelines -
LVEF absolute  > 10 % units and < 50 %
Schwartz RG. Am J Med 1987
ANTRACYCLINES
INTERRUPTION
CARDIOTOXICITY
ONCOLOGICAL
IMPLICATIONS
CARDIOLOGICAL
IMPLICATIONS
ONCOLOGICAL IMPLICATIONS
LIMITATION TO TREATMENT
LVEF < 30%
LVEF 30-49%
SHOULD NOT
RECEIVE
ANTRACYCLINE
ANTRACYCLINE ADAPTED DOSE
Am J Med 1987
STOP IN CASE OF FURTHER
LVEF REDUCTION >10%




703 patients (216 males)
age 47±12 years
treated with HDC
poor prognosis malignancies
♫ Follow-up = 48 months
♫ MACE incidence
 TnI serum determination:
 Baseline
= before HDC
 Early
= soon after HDC (0,12,24,36,72 hours)
 Late
= 1 month after HDC
Circulation 2004
Results
n = 63 pts (9%)
TnI +/+
n = 145 pts (21%)
TnI +/-
n = 495 pts (70%)
TnI -/-
Left ventricular ejection fraction
(%)
65
TnI -/-
60
55
50
*
45
*
*
40
0
1
3
* = p<0.01 vs. TnI -/-;
6
*
*
*
§*
§*
§*
12
18
TnI +/TnI +/+
48
months
§= p<0.01 vs. TnI +/-.
Cardinale et al. Circulation 2004
Cardiac Events
3.5 year-follow-up
Sudden death
Cardiac death
Acute pulmonary edema
Heart failure
Asymptomatic LVEF >25%
Life-threatening arrhythmias
Conduction disturbances
requiring PM implantation
*= p<0.001 vs. TnI -
Negative Transient Persistent
TnI +
TnI
TnI +
* #
#= p<0.001 vs. TnI +-
84%
37%*
1%
Circulation 2004
Cardiac risk stratification
Persistent TnI+
=
High risk
Transient TnI+
=
Intermediate risk
Negative TnI
=
Low risk
Positive predictive value = 84% Negative predictive value = 99%
Troponin I Early Positivity
443 pts
High-dose CT
TnI + = 114 pts (24%)
Enalapril
 n = 56 pts
 started 1 month after HDC
 continued for 1 year
Controls
 n = 58 pts
 physical examination, ECG, ECHO: b,1,3,6,12 months
Secondary end-points:
Follow-up 12 months
Total
n=112
ACEI
n=54
Sudden death
Cardiac death
Acute pulmonary edema
Heart failure
Life-threatening arrhythmias
0 (0%)
2 (2%)
4 (2%)
14 (12%)
11 (10%)
0
0
0
0
1
(0%)
(0%)
(0%)
(0%)
(2%)
CUMULATIVE EVENTS
31 (28%) 1 (2%)
Controls
n=58
P
0 (0%)
NS
2 (3%)
NS
4 (3%)
NS
14 (22%) <0.001
10 (16%)
0.01
30 (52%)
0.001
Cardinale et al. Circulation 2006
There is evidence that cardiac protection
agents may be useful to minimize toxicity
Lipshultz, et. al. NEJM. 2004. 351:145-53.
Valsartan for Prevention of
Cardiotoxicity
Cancer 2005; 104:2492-8
Comparison of LVEF at Baseline
and After Chemotherapy
Data expressed as mean values.
Kalay et al. JACC. Dec 2006. 48:2258-62
LET’S VOTE!
Question # 2
• Which of the following agents from RCT have been
shown to reduce the incidence of Left Ventricular
Systolic Dysfunction?
A) Carvedilol
B) Valsartan
C) Dexrazoxane
D) A and B
E) All of the above
Limited Time to start therapy
Journal of American College of Cardiology January 2010
Responders have less Cardiac event
rates
Journal of American College of Cardiology January 2010
LVEF Changes with Withdrawal of
therapy
AHA 2008
Withdrawal of Heart Failure Therapies
American Heart Association 2008
Paradigm Shift
New Targets/New Agents
Monoclonal Antibodies
Molecular Oncogene
Products
(Erb B 1-4)
Host support tissue
neovasculature
extracellular matrix
Trastuzumab
(Herceptin)
Bevacizumab (Avastin)
Small Molecules
Imatinib (Gleevec)
Sunitinib (Sutent)
Bevacizumab
Sorafenib/Sunitinib/ZD6474/PTK ZK
Sorafenib
Biochem. Soc. Trans. (2003) 31, 1171-1177
Things to Consider
• More than 500 known tyrosine kinases from Human
Genome Project
– Over 250 of these tyrosine kinases are cloned, and
expressed
– 7 Tyrosine Kinases are FDA approved
– 4 Tyrosine Kinases targeted (17 kinases in vivo)
– How many kinases in the human genome are cardiac
specific?
ATP-Binding Sites
• Selective ATP competitive kinases, but difficult to “dial
out” some extra activities (RAF, PDGF, from ABL
inhibitors)
• Beneficial if inhibition of the “extra” targets add to the
therapeutic value of the kinase rather than adverse
toxicity such as collateral cardiac damage. “ A Drive By
Inhibition”!
Mass spectrometric analysis of kinobead purifications from 14 human and rodent cell lines and tissues (human HEK 293, HeLa, Jurkat, K562,
Ramos, THP-1, kidney, placenta; mouse heart, liver, brain, muscle, kidney; and rat RBL-2H3) identified 307 kinases (269 human and 196
rodent) across all branches of the phylogenetic tree. Kinases that were found both in human and rodent samples are shown as green dots,
whereas those specific for either human or rodent are shown in blue or red, respectively. Kinase tree adapted with permission from Cell
Signaling Inc. (http://www.cellsignal.com/). Nature Biotechnology 25(9)2007.
Imatinib is highly selective
Tyrosine Kinase Inhibitor
Kinase-binding profiles of the ABL inhibitors imatinib (upper panel), dasatinib (middle panel),
and bosutinib (bottom panel) across a set of protein kinases simultaneously identified from
K562 cells. The bars indicate the IC50 values, defined as the concentration of drug at which halfmaximal competition of kinobead binding is observed.
Nature Biotechnology 25(9)2007
Drug-Induced Hypertension of
FDA-Approved Cancer Therapies
DRUG AND THERAPEUTIC CATEGORY
HYPERTENSION (%)
Monoclonal antibodies
Bevacizumab (Avastin)
Sunitinib (Sutent)
Hypertension ( 23% to 34%
vs. 14%, severe life-threatening)
Hypertension (>15%)
Alemtuzumab (Campath)
Hypertension ( 11%)
Gemtuzumab (Mylotarg)
Hypertension ( >5%)
Infliximab (Remicade)
Hypertension (10%)
Muromanoab-CD3 (Orthoclone® OKT 3)
Hypertension ( < 1%)
Rituximab (Rituxan)
Sorafenib (Bay49-3006)
Hypertension (6%)
Hypertension (17%)
Common Terminology Criteria for Adverse
Events (v3.0) Grading of Hypertension
Grade
0
1
2
3
4
5
Adverse Event
None
Asymptomatic, transient (≤24 hours) increase by > 20 mmHg (diastolic) or to >150/100
mmHg if previously within normal limits; intervention not indicated
Recurrent of persistent (≥24 hours) or symptomatic increase by
> 20 mmHg (diastolic) or to >150/100 mmHg if previously within normal limits;
monotherapy may be indicated
Requiring more than one drug or more intensive therapy than previously
Life-threatening consequences (e.g., hypertensive crisis)
Death
Clin J Onco Nursing;2005:9(4);407-11
The Definition of “Uncontrolled Hypertension”
varies in Oncology Clinical Trials
JNC 7 Blood Pressure Classification
Blood Pressure Classification
Normal
Prehypertension
Stage 1 hypertension
Stage 2 hypertension
Clin J Onco Nursing;2005:9(4);407-11
Systolic Blood Pressure Diastolic Blood Pressure
(mmHg)
(mmHg)
<120
120-139
140-159
≥160
<80
80-90
90-99
≥ 100
Drug-Induced HF of FDA-Approved
Targeted Cancer Therapies
Drug
Action
Approval
CHF
Sorafenib (Nexavar)
2007
VEGF1,2,3/PDGF
1%
Dasatinib (BMS-354825)
2006
BCR-ABL/SRC
C-Kit,PDGF
4%
Sunitinib (Sutent)
2006
VEGF/PDGF/
C-KIT
3-14%
Bevacizumab (Avastin)
2004
VEGF
2-14%
Everolimus
2010
mTor/VEFG/HIF-1
?
Temsirolimus (Torisel)
2007
mTor/VEFG/HIF-1
?
Hypothetical Mechanism of Hypertension
and VEFG
Acetylcholine
EDRF
Sunitinib/PDGF?
Endothelium
Nitric oxide (NO•)
nitroprusside
NO
Soluble guanylate
cyclase
Vascular smooth
muscle
GTP
Relaxation
cGMP
FDA Approved Targeted Therapies
HTN/CMP
Responds
to ACE/BB
Sorafenib (Nexavar)
CMP
Yes
SHF
Dasatinib (BMS-354825)
CMP
Yes
SHF
Sunitinib (Sutent)
HTN/CMP Yes
SHF/DHF
Bevacizumab (Avastin)
HTN/CMP Yes
SHF/DHF
Trastuzumab (Herceptin)
CMP
Yes
SHF
Imatinib (Gleevec)
CMP
Yes
SHF
Drug
SHF/DHF
Sunitinib Experience in North America
Institution
Sample Size Incidence
SHF/DHF
Dana Farber
(Lancet)
98
8%
SHF
Stanford
(ASCO-GU)
48
12.5%
SHF
MD Anderson
(Cancer)
1100
3%
SHF/DHF
MRCC Registry
1200
21%
SHF
MSKCC
(JAMA)
106
10%
SHF
Hypertension, Potentially Leading to Heart Failure, Associated
with Anti-Vascular Endothelial Growth Factor Therapy Can Be
Predicted by Baseline Levels of Circulating Serum Biomarkers
Figure 1: Levels of VEGF-A and IL-6
prior to treatment with sunitinib or sorafenib
HFSA 2008
VEGF HTN Management
Initial Assessment, Surveillance, and Management of
Blood Pressure in Patients Receiving Vascular
Endothelial Growth Factor Signaling Pathway
Inhibitors
Michael L. Maitland, George L. Bakris, Henry R.
Black, Helen X. Chen, Jean-Bernard Durand, William
J. Elliott, S. Percy Ivy, Carl V. Leier, JoAnn
Lindenfeld, Glenn Liu, Scot C. Remick, Richard
Steingart, W. H. Wilson Tang, Cardiovascular
Toxicities Panel, Convened by the Angiogenesis
Task Force of the National Cancer Institute
Investigational Drug Steering Committee
J Natl Cancer Inst 2010;102:1–9
Hypertension is a Biomarker of
Efficacy in Patients with
Metastatic Renal Cell Carcinoma
Treated with Sunitinib
BI Rini,1 DP Cohen,2 DR Lu,2 I Chen,2 S Hariharan,3 RA
Figlin,4 MS Baum,5 RJ Motzer5
1Cleveland
Clinic Taussig Cancer Institute, Cleveland,
OH; Pfizer Oncology, 2La Jolla, CA, 3New York, NY;
4City of Hope National Medical Center, Duarte, CA;
5Memorial Sloan-Kettering Cancer Center, New York,
NY, USA
57
Study Design
• HTN was defined by both maximum and mean SBP
≥140 mmHg and
DBP ≥90 mmHg as measured in the clinic.
• Sunitinib was administered at a starting dose of 50
mg orally once daily on Schedule 4/2.
• Anti-HTN medications and/or sunitinib dose
schedule modifications were used to manage HTN
as per each clinical trial protocol.
1Motzer
3Motzer
RJ, et al. J Clin Oncol 2006;24:16–24; 2Motzer RJ, et al. JAMA 2006;295:2516–2524;
RJ, et al. N Engl J Med 2007;356:115–124; 4Gore ME, et al. Lancet Oncol 2009;10:757–763.
58
Blood Pressure Assessment
and HTN Status
• Of 544 patients included in the efficacy analysis (after cycle 1, day
1):
– 441 (81%) had HTN as defined by maximum SBP ≥140 mmHg
– 362 (67%) had HTN as defined by maximum DBP ≥90 mmHg.
• Most patients reached maximum BP within the first 3 treatment
cycles.
• With HTN
160 (140–220) mmHg
– Median (range) maximum SBP / DBP =
98 (90–129) mmHg
• Without HTN
– Median (range) maximum SBP / DBP =
130 (100–139) mmHg
82 (59–89) mmHg
• Relative sunitinib dose intensity did not correlate with maximum
SBP (r=–0.072).
59
Clinical Outcome by HTN Status
Max. SBP
≥140 mmHg
(n=441)
Max. SBP
<140 mmHg
(n=93)
P-value
241 (54.6%)
9 (9.7%)
<0.0001
Progression-free survival, months
12.5
2.5
<0.0001
Overall survival, months
30.5
7.8
<0.0001
Max. DBP
≥90 mmHg
(n=362)
Max. DBP
<90 mmHg
(n=172)
P-value
207 (57.2%)
43 (25.0%)
<0.0001
Progression-free survival, months
13.4
5.3
<0.0001
Overall survival, months
32.1
15.0
<0.0001
Objective response, n (%)
Objective response, n (%)
60
Probability of overall survival
Median OS by Use of Anti-HTN Agents, HTNinduced Dose Reductions and HTN status as
Defined by Maximum SBP ≥140 mmHg on Sunitinib
1.0
0.9
0.8
0.7
0.6
0.5
0.4
0.3
0.2
0.1
0.0
Dose reduction only
Anti-HTN drug only
Both
Neither
No HTN
0
5
10
15
20
25
30
Time (months)
35
40
45
50
61
Which Antihypertensives are Better
Suited for TKI’s?
Agent Class
Agent
Initial Dose
Maximum dose
Hepatic metabolism
Nifedipine XL
Felodipine
30 mg/d
2.5 mg/d
90 mg/d
10 mg/d
CYP 3A4
CYP 3A4
(CYP 3A4 inhibitor)
Metoprolol
Atenolol
25 mg BID
25 mg/d
100 mg BID
100 mg/d
CYP 2D6
None
ACEIs
Lisinopril
Captopril
Enalapril
5 mg/d
12.5 mg TID
5 mg/d
40 mg/d
50 mg TID
40 mg/d
None
CYP 2D6
CYP 3A4
ARBs
Candesartan
Valsartan
4 mg/d
80 mg/d
32 mg/d
160 mg/d
CYP 2C9
Inhibits CYP 2C8/9
(weak)
 &  Blocker
Carvedilol
6.25 mg BID
25 mg BID
CYP2C8/9 & CYP2D6
Vasodilator
Minoxidil
5 mg/d
100 mg/d
Glucuronidation
DHP-CCB
Selective  Blockers
J Clin Oncol 24: 1329, 2006
JNC 7: Antihypertensive Drug Classes
for High-Risk Hypertensive Conditions
Recommended Drugs
High-Risk Condition
With Compelling
Indication
HF
ThiazideType
Diuretic
•
-Blocker
•
•
Post-MI
ACEI
•
•
High Coronary
Disease Risk
•
•
•
Diabetes
•
•
•
•
Chronic Kidney
Disease
Recurrent Stroke
Prevention
•
•
ARB
CCB
•
•
•
•
•
Aldosteron
e
Antagonist
Clinical Trial Basis
•
ACC/AHA HF
Guidelines, MERITHF, COPERNICUS,
CIBIS, SOLVD, AIRE,
TRACE, Val-HeFT,
RALES
•
ACA/AHA Post-MI
Guidelines, BHAT,
SAVE, CAPRICORN*,
EPHESUS
•
ALLHAT, HOPE,
ANBP2, LIFE,
CONVINCE
•
NKF-ADA Guidelines,
UKPDS, ALLHAT
NKF Guidelines,
Captopril Trial,
RENAAL, IDNT,
REIN, AASK
PROGRESS
LET’S VOTE!
Question # 3
• When initiating Antihypertensive Therapy,
the following considerations should be
considered;
A) Underlying Co-Morbid conditions
B) Baseline Renal Function/proteinuria
C) Drug/Drug Interaction
D) All of the above
Heart Failure Specialist Perspective
Continuum of Cancer Intervention
Lymphoma Patient-R-Chop
Cycle 1
Cycle 2
Baseline
ECG
BNP/Troponin
Echo/Strain
(+) Echo,
Consider
Ace/BB?
Troponin
BNP
(-) proceed,
Cycle 3
BNP/Troponin
Cycle 4
BNP/Troponin
(-) proceed,
(-) proceed,
(+) Echo,
Consider
Ace/BB?
(+) Echo, Consider
Ace/BB?
Continue Chemo
Continue Chemo
ECG HR<60 (Qtc)
Any symptoms
Continue Chemo
Stop dox LVEF<40%
LET’S VOTE!
Question # 4
• 56 year old patient with history of Breast Ca
treated with FAC, now has progression of disease.
Her-2-Neu +++ progressed with Trastuzumab now
on Avastin. Had LVEF of 45% with no symptoms.
BP=141/85
• What is your therapy of choice?
A)Start Carvedilol
B) Start ACE-inhibitor or ARB
C) Start Both
D) Neither
Future of TKI’s in Drug Development
• Hypertension is a significant problem in drug
development and no current guidelines or consensus
exist regarding its MOA or treatment
• Need for early treatment prior to starting therapy and
define control of hypertension during chemotherapy
• Treatment modalities should consider Non-invasive
Cardiac performance and less dependence on LV
ejection fraction
• Need greater understanding of specific agents on
pathways of proliferation, angiogenesis and stresspathways as it relates to new therapies, i.e. nonselective beta blockers, ARB
Conclusions
• Exciting new cancer therapies are being discovered,
however, in order to maximize their potential, cardiac
toxicities need to be identified and addressed upfront
• Cardiologists should collaborate with oncologist in trial
design
• Although recent clinical experience has shown
significant cardiotoxicity post-trial with cancer
therapies, we have also seen resolution of toxicity
using evidence-based cardiology guidelines
• In order for continued success in making cancer history
– cardiology and oncology must align their goals in
clinical and translational research
• [email protected]
Conclusions
Organizations for future:
•
•
•
•
Conquer- MD Anderson Cancer Center
Cardiology Oncology Partnership Vanderbilt USA
International Society for Cardioncology Milan, Italy
Brazilian Cardiology Oncology 2009 Sao Paulo, Brazil
Question & Answer
• Please wait for the microphone to ask your
question so all participants can benefit from
the discussion
Case Presentations
and Discussion
Rama Balaraman, MD
Medical Oncologist/Hematologist
Ocala Oncology
Ocala, Florida
68 year old with diarrhea
• After extensive work up found to have carcinoid
• Sandostatin LAR started
• Great diarrhea control
• But BP is now 190 /90 and patient feels great
70 year old with SOB
• Non smoker
• After biopsy diagnosed with adenocarcinoma
• Started treatment with tarceva
• Did well with no sob for 18 mts
• Then progressed on scans
• Added avastin to tarceva
• Patients pet scan dramatically better after 4 doses
• After one year on tarceva avastin c/o increasing sob
• Rpt scans show stable disease but BP –150 /90
59 year old with hematuria
• Work up shows renal cell cancer with pulm mets
• Started on sutent
• Patient feels better in 8 weeks except fatigue
• Now BP is 180/90
80 year old with increased wbc
• Flow shows aml –m2
• No medical problems except minor deafness
• Should we treat her
• Should we get cardiac evaluation before initiating
• Treatment??
• If so what tests??
Postsession Survey
Please take a moment
to answer the postsession survey
questions
Question # 1
• 56 y/o patient with breast cancer Her-2-Neu
positive. No h/o DM. Present for treatment
with Trastuzumab
• BP on presentation to clinic was 168/92.
What is your treatment of choice for HTN?
A) Start Beta Blocker
B) Start Ace-Inhibitor or ARB
C) Neither, start Trastuzumab immediately
D) A and B
Question # 2
• Which of the following agents from RCT have been
shown to reduce the incidence of Left Ventricular
Systolic Dysfunction?
A)Carvedilol
B)) Valsartan
C) Dexrazoxane
D) A and B
E) All of the above
Question # 3
• When initiating Antihypertensive Therapy,
the following considerations should be
considered;
A) Underlying Co-Morbid conditions
B) Baseline Renal Function/proteinuria
C) Drug/Drug Interaction
D) All of the above
Question # 4
• 56 year old patient with history of Breast Ca
treated with FAC, now has progression of disease.
Her-2-Neu +++ progressed with Trastuzumab now
on Avastin. Had LVEF of 45% with no symptoms.
BP=141/85
• What is your therapy of choice?
A)Start Carvedilol
B) Start ACE-inhibitor or ARB
C) Start Both
D) Neither
Closing Remarks
Rama Balaraman, MD
Medical Oncologist/Hematologist
Ocala Oncology
Ocala, Florida