MD Conference Express AHA 2013 - (Page 41)
events, but outpatient primary chemoprophylaxis is not
currently advocated in the national guidelines due to lack of
adequate data determining long-term safety and mortality
benefit [Streiff M et al. J Natl Compr Canc Netw 2013; Lyman
G et al. J Clin Oncol 2013]. Risk stratification tools are
needed to determine which patients may benefit the most
from primary outpatient VTE chromoprophylaxis. The
best validated model to date to predict cancer associated
thrombosis was developed by Khorana et al. [Blood 2008].
The Khorana score uses five variables: site of cancer,
platelet count, hemoglobin and/or use of erythropoiesisstimulating agents, leukocyte count, and body mass index
of ≥35 kg/m2 to predict which patients are at highest risk for
incident thrombosis. A Phase 3 randomized trial to evaluate
the utility of primary prevention among patients with high
VTE risk is currently ongoing [NCT00876915]. In addition,
the ongoing discovery of novel biomarkers associated with
incident VTE, will likely help us build better prediction
scores in the future.
Figure 2. Incidence Rate of VTE Versus Cancer Type Mortality
20. Cancer; Fig3
Breast
Prostate
Bone
Colorectal
Hematologic
Brain
Lung
Pancreas
Incidence Rate per 1000 Person-Years
100
75
50
25
0
0
25
50
1-Year Relative Mortality (%)
75
trials in women with surgically removed HER2-positive
breast cancer treated with trastuzumab showed significant
(p=0.0001) improvement in disease-free survival at 4 years
[Romond EH et al. N Engl J Med 2005].
Although there is some risk of cardiac dysfunction with
the addition of trastuzumab to adjuvant chemotherapy
in these patients, the benefits of outweigh the risks, and
cardiac toxicity, if it develops, can be managed [Romond
EH et al. J Clin Oncol 2012]. Assessment of left ventricular
ejection fraction (LVEF) prior to initiation of trastuzumab
and at regular intervals during treatment is recommended
[Herceptin (trastuzumab) Highlights of Prescribing
Information. South San Francisco, CA: Genentech; 2013
(rev)]. The standard of care is 12 months of trastuzumab
treatment [Pivot X et al. Lancet Oncol 2013]. ACE inhibitors
are recommended for HER2 patients with LVEF <40% with
no signs and symptoms of heart failure (asymptomatic
LV dysfunction) [Heart Failure Society of America.
J Card Fail 2010].
Many chemotherapy agents that are routinely used
have been associated with cardiotoxicity. Apostolia M.
Tsimberidou, MD, PhD, University of Texas M.D. Anderson
Cancer Center, Houston, Texas, USA, discussed the various
cancer therapies and the cardiac dysfunction associated
with their use. The use of agents such fluorouracil,
interleukin-2, and sorafenib are associated with ischemia.
QT prolongation associated with arrhythmias can result
from thalidomide and vandetanib use. LV dysfunction
is seen with anthracyclines, trastuzumab, and antivascular endothelial growth factor drugs such as sunitinib,
bevacizumab, and pazopanib.
Changes in the management of cardiotoxicity in
cancer patients receiving chemotherapy, improved patient
screening and monitoring, identifying patients at increased
risk, and establishing standardized procedures and
decision support systems, have helped improve outcomes.
Reproduced with permission from A Tafur, MD.
Patients who develop VTE, have a lower likelihood of
thrombosis recurrence with no increased risk of bleeding
if treated with low-molecular weight heparin (LMWH)
compared with warfarin [Lee AYY et al. N Engl J Med 2003].
Therefore, LMWH is currently the preferred treatment for
cancer associated VTE. To date, the data evaluating novel
anticoagulants in the specific setting of active cancer is
limited and such agents should not be used as primary
treatment option.
The unlabeled use of trastuzumab for the treatment of
human epidermal growth factor receptor 2 (HER2)-positive
breast cancer was the topic of discussion by Richard
Steingart, MD, Memorial Sloan-Kettering Cancer Center,
New York, New York, USA. The combined results from two
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