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Oncology 421

The "EdPrezi" primer on options for education change
by

Yasmin ELSobky

on 1 November 2014

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Transcript of Oncology 421


Leukemia

education
environment
global
economic
opportunity
Help!
I'm Lost in the Weeds!
How do I even think about education change? The topic is too big!!!
We thought, "Hey, let's make it easier for
Full Circle members to
learn about education change ideas!
anyone
...and where to look for more!
...and how to get involved!
...and invite readers
to comment/contribute!
Acute Myelogenous Leukemia
Tumor Lysis Syndrome
Treatment of AML
Chronic leukemia
...that $upports...
What is leukemia?.
1
2
3
4
5
6
7
education
Acute lymphocytic (lymphoblastic) leukemia
What is leukemia?
Bone Marrow Suppression
What is Acute Myeloid Leukemia (AML)?
Etiology
Epidemiology
Morphologic Classification of Myeloid LeukemiaFrench-American-British (FAB)
AML: Cytogenetics
AML : Age-Related Differences in
Molecular Mutations
AML: Signs and Symptoms
What is TLS?
Risk of TLS
Prevention and monitoring strategies
Infectious Complications
Infectious Complications
Common Pathogens
White Blood Cell
Growth Factors
Role of Transplantation
Strategies of post remission therapy
Bone Marrow Tranplantation
(Hematopoetic Stem Cell Transplantation)
Treatment Issues
Case Study
Etiology in Adults
ALL – Physical Findings
ALL – Laboratory Data
Classification of Lymphoid Leukemia
ALL: induction
Treatment Strategies in Adults.
Treatment Strategies in Adults
ALL:
Treatment Strategies in Adults
ALL: CNS Involvement
Chronic Leukemia
Chronic Myelogenous Leukemia
Chronic Phase
Goals of therapy:
Accelerated Phase
Goals of therapy
Blast Crisis
Chronic Lymphocytic Leukemia
Case Study
2.1
Should classes be the same size, no matter what?
Some teachers manage large classes rather well.
Should they be paid more?
.org
more on
http://ed100.org
.org
education
So... What Can I do?
Policy
Advice
The Unit of Change is EACH
education
education
education
The Goal of CR
education
education
education
education
education
Risk Grouping for AML: Cytogenetics
education
education
education
education
education
education
education
education
Hematopoietic growth factors
education
Tip: Are you viewing this Prezi full screen?
Use the "More" button below, on the right side.
"Ahhh, that's better!"
Oncology
An Overview of Leukemia:
Focus on Pharmacy Practice
“ The leukemias are heterogenous hematologic malignancies characterized by unregulated proliferation of the blood-forming cells of the bone marrow.”
Acute leukemia: immature cells (blasts)
Blast crowd out production of normal cells
Blast may infiltrate tissue
Chronic leukemia: mature cells
Types of Leukemia
Acute Leukemia
Chronic Leukemia
Chronic myelogenous leukemia
Chronic lymphocytic
leukemia
Acute myelogenous
leukemia
Acute lymphocytic
(lymphoblastic) leukemia
JW is a 66 y/o female admitted to the hospital with newly diagnosed acute myelogenous leukemia (AML).
flu-like symptoms X 3 wks  treated with antibiotics
bruising noted on physical exam when she presented to physician for management of “resistant flu”
Laboratory:
WBC 63 x 103/cu mm
blast 75%
platelets 50 K
Hgb 10 gm/dl
creatinine 2.6 mg/dl

Physical Exam:
temp 39° C P:68 BP:140/72 R:30
indwelling central venous catheter (new)
CBC:
 High white blood cell count WBC
presence of peripheral blasts.
Bone marrow biopsy and aspirate diagnosis of AML (M2)

Social / Family history:
married with 2 grown children
retired physican
parents alive and live locally
three sisters
AML is a heterogeneous group of malignant diseases of hematopoietic progenitor cells
characterized by their
lack of maturation
leukemia progenitor cells inhibit normal hematopoietic maturation
At least 20% of cells in peripheral blood or bone marrow are blasts that are
myeloid
in origin.
(World Health Organization 1999)
Increase incidence in higher socioeconomic groups
increase treatment-related MDS and treatment-related leukemia in survivors of childhood cancer
rate of AML rises after the age of 50 y/o
- increase of myelodysplastic syndrome
- increase of secondary AML
the cause of AML in most cases is
unknown
believed to be caused by a
genetic predisposition
combined with
exposure to toxins
chemotherapy (t-AML)
alkylating agents 5 - 10 yrs after treatment
topoisomerase II inhibitors (e.g. etoposide)
radiation
viruses
cigarette smoke
environmental carcinogens
Benzene
Electromagnetic radiation
M0
undifferentiated; blast cells express myeloid antigens
M1
acute myeloblastic leukemia with minimal differentiation
M2
acute myeloblastic leukemia with maturation
M3
acute promyelocytic leukemia
M4
acute myelomonocytic leukemia
M5
acute monoblastic leukemia without differentiation
M5
acute monoblastic leukemia with differentiation
M6
acute erythroleukemia
M7
Megakaryocytic leukemia
Cytogenetics are an important
prognostic factor
in patients with newly diagnosed AML
patients with normal karyotype : 30 - 35%
patients with favorable karyotype: < 30%
there is a variation in response to treatment with each cytogenetic group
Karyotype Incidence(%) CR(%)
favorable:
t(8;21) 5-10 90
inversion 16 5-10 90
t(15;17) 5-10 80-90
intermediate:
diploid, -y 40 - 50 70-80
unfavorable:
-5,-7 20-30 40
+8 10 60
11q23, 20q- 10-20 60
Better Risk:
normal cytogenetics with isolate NPM1 mutation
Intermediate Risk:
- c-KIT in patients with t(8;21) or inv(16)
Poor Risk:
- normal cytogenetics with isolated FLT3 mutations
abnormal blood counts
Abnormal white blood count
decrease red blood cells (anemia)
decrease in platelets (thrombocytopenia)
peripheral blasts
increased LDH
signs of TLS

change in white blood cell count
30 % patient have increase WBC (may cause pain)
30 % patients have decrease in WBC
30% patients have normal WBC
bone marrow failure
 dec. red blood cell (RBC)
 dec. platelets
 dec. WBC
 dec. functioning neutrophils
extramedullary tissue invasion
skin lesions are called chloroma
tumor cell break down–can lead(TLS)
Clinical manifestation of AML
Bone marrow depression from leukemia:
abnormal WBC count:
 high WBC - leukostasis of blood flow
 decrease WBC (neutropenia) increase risk of infection
decrease red blood cells (anemia)
fatigue, malaise, weakness, Cardiac effects
decrease in platelets (thrombocytopenia)
risk of bleeding
TLS is a metabolic oncologic emergency characterized by hyperuricemia, hyperkalemia, hyperphosphatemia and hypocalcemia.
Patients with
high

tumor burden
( WBC, blasts, LDH)
tumors with high, rapid growth fraction
chemoresponsive tumors (AML)
Complications of TLS:
hyperuricemia
renal failure
K+, PO4, Ca+
AML: Prognostic Factors
Age
Etiology
FAB classification
Cytogenetics
Molecular mutations
Response to treatment
LDH
TLS is a metabolic oncologic emergency characterized by cell break down:
Hyperuricemia ( high uric acid) which lead to renal failure
Hyperkalemia ( high potassium)
hyperphosphatemia (high phosphorus)
Hypocalcemia (decrease calcium)
Risk of TLS:
patients with high tumor burden ( WBC,  blasts,  LDH)
tumors with high, rapid growth fraction
chemoresponsive tumors (AML)
- initiate with diagnosis
- loading dose maybe needed if treatment to start immediately
Prevention strategies:
hydration
maintain urine output
allopurinol
rasburicase
- choice and rate of hydration should be based on patient factors
Electrolyte Management
(Elitek)
Recombinant form of
urate oxidase
 acts as a catalyst in enzymatic oxidation of uric acid to allantoin (> solubility than uric acid)
Pros
Cons
5+7=
(cc) image by anemoneprojectors on Flickr
- rapid onset of action ( UA within 2 - 4 hrs)
- does not increase xanthine or hypoxantine
- no drug interactions with 6MP
- cost
- derived from protein from Aspergillus flavus
hypersensitivity: quick onset,  with subsequent use
risk of hemolysis with 6GPD
Rasburicase
Neutropenia
extended period of neutropenia associated with
increase infection
role of prophylactic anti-infectives
empiric antibiotics
? role of colony stimulating factor
Risk Factors for Infection:
absolute neutropenia (ANC < 500)
ANC = WBC x (% neutrophils + % bands)
disruption of the normal mucosal barriers
secondary infections
with use of antiinfectives
environment
(hospital versus home)
Historically:
bacterial pathogens:
gram -ve aerobes trend toward gram +ve bacteria
Emergence of antibiotic resistant bacteria
secondary fungal infections
colony stimulating factors (CSF) or hematopoetic growth factors
proteins  stimulate white blood cells
G-CSF and GM-CSF have been given
after
chemotherapy to accelerate neutrophil recovery and reduce infectious mortality
commonly use d after chemotherapy for solid tumors with high risk of prolonged neutropenia
Associated with:
Dec. duration of neutropenia
Dec. risks associated with neutropenia
allows subsequent courses of chemotherapy to be given on time
G-CSF and GM-CSF have been given
after
induction chemotherapy
to accelerate neutrophil recovery and reduce infectious mortality.
- shorten period of neutropenia btw 2-7 days
- decrease in infection rates (some studies)
- decrease in infectious mortality (some studies)
- no consistent benefit on CR rate or overall survival (OS)
Concern (no support) - Does G-CSF and GM-CSF increase leukemia cells?
Hematopoetic Growth Factors:G-CSF
(granulocyte colony stimulating factor)
GM-CSF
(granulocyte macrophage colony stimulating factor)
Names or terms:
colony stimulating factors
hematopoetic growth factors
white blood cell growth factors
Use:
- given after chemotherapy to minimize the impact of chemotherapy on suppression of neutrophils
Potential problems:
concern with use is AML unless the leukemia has been adequately treated
can be used in ALL
Bone Marrow Suppression
Thrombocytopenia
menses suppression
birth control
gastric ulcer prophylaxis
management of bleeding episodes
education
goal is to prevent / delay relapse
Autologous HSCT
Donor: patient
Allogeneic HSCT
Donor: family (MRD)
Donor: donor bank (MUD)
Syngenic HSCT
Donor: identical twin
Role of HD Chemotherapy + Allogeneic HSCT:
- hematopoietic reconstitution following HD chemotherapy
- graft-versus-leukemia effect
Refractory AML
Relapsed AML
Treatment of older patients with AML
AML in pregnancy
Acute Promyelocytic Leukemia M3
APL is a
subclass
of AML
APL accounts for 10% of all AML cases
Considered the most curable of the AML subtypes
Differentiation and maturation arrest are caused by alteration of the retinoic acid receptor
because of translocation of chromosomes 15 and 17



Associated with disseminated intravascular coagulation (DIC) with diagnosis and cytotoxic chemotherapy
Chronic myelogenous leukemia
Chronic lymphocytic leukemia
Chronic leukemias are distinguished by uncontrolled expansion of mature cells; onset is slow
Leukemic cells crowd out normal cells causing disruption in normal hematopoiesis
Phases of Disease:
CML chronic-phase:
- resembles benign expansion of myelopoiesis
progresses to clonal evolution
typical duration 1 – 4 years without treatment

CML accelerated phase:
molecular and chromosomal abnormalities

CML blast phase:
- impairment of hematopoietic differentiation AML or ALL
Maintain chronic phase
Symptomatic control of WBC and splenomegaly
Delay progression to accelerated phase / blast crisis

Treatment
Tyrosine kinase inhibitors (imatinib)

Induction chemotherapy or targeted agents to return to a second chronic phase (not definitive therapy)
Treatment
tyrosine kinase inhibitors (imatinib, dasatinib, nilotinib)
Stem cell transplant
education
Goals of therapy
Induction chemotherapy or targeted agents to return to a second chronic phase

Treatment
Tyrosine kinase inhibitor
Induction chemotherapy
ALL-type chemotherapy for lymphoid blast crisis
AML-type chemotherapy for myeloid blast crisis
Allogeneic stem cell transplant
Clinical trial
Clonal expansion of small lymphocytes accumulating in the marrow, lymph nodes, blood, spleen, liver and other organs.
LEARNING OBJECTIVES
Upon completion of the chapter, the reader will be able to:
1. Describe the pathogenesis of acute leukemia.
2. Compare the classification systems for acute lymphocytic leukemia (ALL) and acute myelogenous leukemia (AML).
3. Identify the risk factors associated with a poor outcome for the acute leukemias.
4. Explain the importance of minimal residual disease (MRD) and its implication on early bone marrow relapse.
5. Explain the role of induction, consolidation, and maintenance phases for acute leukemia.
6. Define the role of CNS preventive therapy for acute leukemia.
7. Recognize the treatment complications associated with therapy for acute leukemias.
8. Describe the late effects associated with the treatment of long-term survivors of acute leukemias.
HPI:
Jenny M. is a 3 year old girl brought to the pediatric clinic by her parents.
Report that for the past week she has been fatigued, and has had fevers, easy bruising and puffiness of the extremities.
PMH:
Up to date on immunizations
No prior surgeries or serious medical problems
FH:
No family history of cancer
SH: not applicable
ROS: not contributory
Medications: none
All: NKDA
Physical Exam
General:
Alert, interactive, well-developed but ill appearing child
VS:
BP 130/83 P 95 RR 34 T 36.8
Ht: 38” Wt: 17.3 kg BSA: 0.6 m2
Skin:
diffuse pallor
random bruises just inferior to the hairline, face and over the proximal upper extremity
petechial-appearing rash over the buttocks and lower left flank
Etiology in unknown in majority of cases
chemical exposure
radiation exposure linked with development of ALL although only found in Japanese atomic bomb survivors
genetic conditions:
Down’s syndrome
Bloom syndrome
Fanconi anemia
Kleinfelter’s syndrome
Pallor
Petechiae
Ecchymoses
Lymphadenopathy
Splenomegaly
Hepatomegaly
Pancytopenia
Most patients present with WBC > 100,000
Elevated LDH, uric acid (correlates with large tumor burden)
t(9;22) Philadelphia (Ph) chromosome most common abnormality in adult ALL
17-25% of cases
Morphologic Classification of Lymphoid LeukemiaFrench-American-British (FAB)
L1

small cells
with minimal cytoplasm
- 30% of adult form
- seen more often
in children
L2

large cells
with moderate cytoplasm and predominant nucleoli
- 60% of adult form
L3
large cells with basophilic cytoplasm
- 10 % adult form
- Burkitt’s type leukemia
Immunophenotyping :
- majority of cells are B lineage
- characteristics consistent with a pre-B cell phenotype
- 25% of adult patients are T-cell lineage
Cytogenetics:
- most common cytogenetic abnormality is 9;22 translocation (30% of adults ALL)
- Philadelphia chromosome is
poor
prognostic indicator
- translocation of 11q23 and 1;9 are associated with
poor
outcomes
- translocation with 12;21 associated with improved prognosis in children
Therapeutic Approaches
Induction Therapy
- goal is to induce a CR
Post Remission Therapy
- goal is to prevent/delay relapse
- intensification
(dose / alternative drugs)
- consolidation
Maintenance Therapy
Historically induction therapy has been built around vincristine + steroid
most modern regimens have intensified the regimen based on poor prognostic factors in adult patient
- asparaginase
- cyclophosphamide
- anthracycline
role of CNS prophylaxis
Prior to therapy:
- patient evaluation issues (eg.sperm banking)
- identification of risk associated with treatment
- evaluation for specific chemotherapy
cyclophosphamide
vincristine
asparaginase
prednisone
- patient/ caregiver education
Induction with 5 drugs:
CTX +VCR +Pred +l-aspar +dauno
Early intensification (course II):
CTX + SQ araC + 6MP+ VCR + sq l-aspar
CNS Prophylaxis + Maintenance:
cranial XRT + 6MP + MTX
Late intensification:
doxo + VRC + dex + CTX + 6TG + cytarabine
Prolonged Maintenance:
VCR + pred + MTX + 6MP

CR: 85% (median survival 45+ months)
Median Survival: 36 months
Failure to achieve CR: 7% (resistance)
9% (early death)
Therapeutic approaches
Vincristine
Mechanism:
vinca alkaloid
microtubule poison
Side Effects:
neurotoxicity
minimal bone marrow depression
vesicant if extravasation occurs
Note:
- NEVER give intrathecal
Corticosteroids in ALL
Chemotherapy
Mechanism:
- anti lymphocyte effect causes cell kill
Side Effects
:
Hyperglycemia
Increase blood pressure
Adrenal suppression
GI upset / bleed
Infection
Note:
- can cause immediate tumor cell break down (TLS)
Mechanism:
alkylating agent
toxicity is dose dependent
Side Effects:
bone marrow suppression
nausea and vomiting
hemorrhagic cystitis
infertility and sterility
secondary cancers
Cyclophosphamide
Acute Leukemia: Infectious Complications
Risk Factors for Infection:
absolute neutropenia (ANC < 500)
disruption of the normal mucosal barriers
secondary infections with use of antiinfectives
environment (hospital versus home)
drug therapy that causes IMMUNOSUPPRESSION
CNS involvement < 5% children and < 10% adults with ALL at diagnosis, but eventual relapse secondary to CNS relapse initiated use of CNS prophylaxis for ALL
CNS relapse occurs in only 5 - 10% of patients treated with contemporary protocols
Prognosis
- age (increase in younger age)
- L3 of FAB classification (mature B cell immunophenotype)
- ? T cell
- disease burden ( increase LDH, high WBC)
- extramedullary involvement
- proliferative disease
Diagnosis :
- presence of 5 WBC/mcL in CSF with morphological lymphoblasts
- presents of blasts in CSF (may have lower WBC)
Treatment Strategies in Adults
Issues with CNS Prophylaxis
optimal timing of therapy
optimal drug / dose / regimen
role of craniospinal irradiaton
effect of systemic chemotherapy
identification of patients at risk of
CNS leukemia
method of administration
(i.e. LP vs omaya reservoir)
==>Constipation
Normally Blasts do not appear in the blood
If it is found
their is a blasts in the bone marrow
http://www.tree.com/health/leukemia-diagnosis.aspx
but some times no blasts appears in blood stream
but their is blasts in the bone marrow
To diagnose Leukemia
By Ways
2
http://www.daviddarling.info/encyclopedia/B/bone_marrow.html
Normal bone marrow contains 5% blasts
Most aggressive
More curable
Translocation
Deletion
Addition
Translocation
Deletion
Addition
Complete response
M0
undifferentiated; blast cells express myeloid antigens
M1
acute myeloblastic leukemia with minimal differentiation
M2
acute myeloblastic leukemia with maturation
M3
acute promyelocytic leukemia
M4
acute myelomonocytic leukemia
M5
acute monoblastic leukemia without differentiation
M5
acute monoblastic leukemia with differentiation
M6
acute erythroleukemia
M7
Megakaryocytic leukemia
Monitoring parameters:
K+
phosphorous
Ca+
renal function
urine output
WBC
Post Remission Therapy
Induction Therapy
cytarabine x 7 days
idarubicin x 3 days
Evaluation of leukemia 10 – 14 days after beginning chemotherapy
Determination of next treatment
Continous infusion
100 - 200 mg /m2/day CI
12 mg /m2 IVP
Anthracycline / anthracycline derivative:
daunorubicin 45 - 60 mg /m2 IVP x 3 days
- or -
idarubicin 12 mg /m2 IVP x 3 days
- or -
mitoxantrone 12 mg /m2 IVP x 3 days
If blast remain in the bone marrow 14-21 days after starting chemotherapy:

Dec in blasts ==>
second course of induction therapy
Bone marrow is hypoplastic
==> second course is delayed until status of marrow is clear
Minimal residual leukemia without circulating blasts:
==> observation for 3 - 7 days and repeat BM
Cytarabine (AraC)
Mechanism of action:
antimetabolite
Dosing: depends on combination and use
Side Effects:
Bone marrow depression
Mucositis
High dose cytarabine used in post remission therapy:
cerebellar toxicity – presents as ataxia, unsteady gait
ocular toxicity – irritation
Skin toxicity
Consolidation
Intensification
intensification ( dose / alternative drugs)
Example: high dose cytarabine
Example: bone marrow transplantation
Goal: is to prevent/delay relapse
Goal: is to induce CR complete remission

high-dose cytarabine (HDAC)
bone marrow transplantation:
HD chemotherapy + allogeneic HSCT
HD chemotherapy + autologous HSCT
Non-myeloablative chemotherapy + allogeneic HSCT
consolidation with similar agents used in
induction therapy
HD cytarabine (HDAC) x 4 courses
100 mg/m2/day x 5 days CI
400 mg/m2/day x 5 days CI
3 gm/m2 q 12 hours x 6 doses (d1,3,5)
Patients < 60 y/o : DFS and OS with high dose cytarabine
Who should receive HD cytarabine?
- pts that benefit most appear to have favorable cytogenetics
- benefits for HDARAC in pts < 55-60 y/o
- older pts receiving HDAC increase toxicity and mortality
Mayer RJ, 1994
Bone Marrow transplantation
the escape of blood into the tissues from ruptured blood vessels
there is a reduction in the number of red and white blood cells, as well as platelets
Induction with 5 drugs:
CTX +VCR +Pred +l-aspar +dauno
Early intensification
(course II):
CTX + SQ araC + 6MP+ VCR + sq l-aspar
CNS Prophylaxis + Maintenance:
cranial XRT + 6MP + MTX
Late intensification:
doxo + VRC + dex + CTX + 6TG + cytarabine
Prolonged Maintenance:
VCR + pred + MTX + 6MP
CR: 85% (median survival 45+ months)
Median Survival: 36 months
Failure to achieve CR: 7% (resistance)
9% (early death)
Prior to therapy:
Prior to therapy:
- patient evaluation issues (eg.sperm banking)
- identification of risk associated with treatment
- evaluation for specific chemotherapy
cyclophosphamide
vincristine
asparaginase
prednisone
- patient/ caregiver education
historically
induction therapy has been built around vincristine + steroid
most modern regimens have intensified the regimen based on
poor
prognostic factors in adult patient
- asparaginase
- cyclophosphamide
- anthracycline
role of CNS prophylaxis


goal is to induce a CR
Post Remission Therapy
- goal is to prevent/delay relapse
- intensification ( dose / alternative drugs)
- consolidation
let's us sum it up
CNS Prophylaxis + Maintenance:
cranial XRT + 6MP + MTX
cranial XRT + 6MP + MTX
cranial XRT + 6MP + MTX
cranial XRT + 6MP + MTX
cranial XRT + 6MP + MTX
cranial XRT + 6MP + MTX
cranial XRT + 6MP + MTX
CR
Median survival
Failure to achieve CR
(cc) image by rocketboom on Flickr
(cc) image by quoimedia on Flickr

An Overview of Breast Cancer :Focus on Pharmacy Practice
Breast cancer
Epidemiology:
breast cancer is the leading cause of cancer death in women world wide

Dec. new cases
- reduction in hormone replacement therapy

decrease mortality
early diagnosis
improved treatment
Genetics:
Familial breast cancer: 5 – 10% of all breast cancer
Tumor suppressor gene mutations (BRCA1 and BRCA 2)
Protooncogene HER2/neu (human epidermal growth factor receptor-2)
Others include c-myc, cyclin D1
Tumorigenesis involves many steps:

atypical hyperplasia


ductal carcinoma in situ



invasive ductal carcinoma
Malignant progression involves early changes in the proliferation of cells
systemic hormones (e.g. estrogen, progesterone)
growth factors
Risk Factors
female
gender
inc. pt
age
FH of it at a young age
Estrogen
exposure
Prolonged hormone replacement therapy
benign breast disease
radiation
exposure
genetic
mutations
obesity
alcohol
physical
activity
prevention
Early Detection
clinical breast examination (CBE) not uniformly recommended
beneficial with mammograms
training of personnel
The Role of Self Examination
Annual screening mammography reduces the mortality from breast cancer in women > 50
Less sensitive in young women with dense breast tissue.
Current controversy:
over management
cost
benefit
Mammograms
Magnetic resonance imaging (MRI)
MRI screening is appropriate as adjunct to mammography in women with the following:
BRCA mutation carrier
increase lifetime risked based on risk models
maybe considered in other high risk women
Prevention
Prevention in women at risk for breast cancer
Prevention in breast
cancer recurrence
prophylactic mastectomies
bilateral oophorectomy
tamoxifen
raloxifene (less effective than tamoxifen preventing LCIS and DCIS)
aromatase inhibitors (clinical trial)
tamoxifen
aromatase inhibitors
low fat diet
Tamoxifen:
(+) reduction in incidence of invasive and noninvasive breast cancers
(+) reduction in invasive breast cancers in women with LCIS and AH
(+) reduction in ER + breast cancer (but not ER – tumors)
(-) increase incidence of endometrial cancer, VTE, cataracts, hot flashes
Raloxifene:
(+) similar reduction in incidence of invasive breast cancers as compared to tamoxifen
(-) endometrial cancer, VTE, cataracts, hot flashes
Raloxifene is approved for reduction in risk of invasive breast cancer in postmenopausal women with osteoporosis and postmenopausal women at high risk for invasive cancer.
Every thing about Breast cancer
Signs + Symptoms
painless lump
breast pain
nipple discharge (not common)
dimpling of breast (not common)
nipple retraction (less common)
inflammatory breast cancer : orange peel
symptoms of metastatic disease ( < 10%)
Pathologic Types
Most breast cancers are adenocarcinomas
Breast Cancer
Invasive Carcinoma
Non-Invasive Carcinoma
invasive ductal carcinoma (IDC) – most common
ductal carcinoma
in situ (DCIS)
lobular carcinoma
in situ (LCIS)
risk factor for breast cancer
invasive lobular carcinoma (ILC)
premalignant
Sites of Metastatic Disease
Bone
Liver
Lung
Brain
Skin
Prognosis
Disease related factors
Staging
Hormone Receptors
Histologic/nuclear grade
Genetics
Gene expression
Metastises
Markers for
angiogenisis
Bone, Liver, Lung, Brain, Skin
TNM Classification
T – primary tumor
T1 :
tumor not > 2 cm greatest dimension
T2
: tumor >2 cm but not > 5 cm greatest dimension
T3
: tumor > 5 cm greatest dimension
T4
: tumor of any size with direct extension to chest wall or skin
T4
d
: inflammatory breast cancer
N – regional lymph nodes
M – distant metastasis
Stage 0
DCIS
cells look like cancer but have not invaded surrounding tissue
Stage I
invasive ductal cancer
cells invade the
duct

no

evidence of lymph node involvement
Stage II
larger tumor size
may have limited spread to LN
Stage III
lymph node involvement
large tumor (T4) with no lymph node involv.
Stage IV
cancer has spread beyond the breast & lymph
Hormone receptors are cytoplasmic proteins that transmit signals to the nucleus of the cell for growth and proliferation
-
50 – 70% women are
hormone receptor +
- more common in
postmenopausal women
Estrogen receptor (ER)
Progesterone receptor (PR)
Hormone receptors help predict response to hormone therapy
amplified /over expression in
25-30% women
more common in
premenopausal
women
used to determine patients who may benefit from drug therapy directed at HER2 neu
trastuzumab therapy
lapatinib therapy
Testing:
- Immunohistochemistry (IHC)
- Fluorescence in-situ hybridization (FISH)
Familial clustering of breast cancer in specific inherited breast-cancer syndromes associated with single gene
BRCA1, BRCA2, PTEN, TP53
rare in general population
account <25% of inherited component of breast cancer
Empirical genomewide association studies have identified breast cancer susceptibility alleles common in the general population
small number of susceptibility alleles could help identify women at
high risk
of breast cancer
Oncotype DX
- genetic test that screens for expression of 21 genes
- used to determine
re
currence score
Application in practice
- determination of risk of recurrence or death from breast cancer in women with HR+,LN-, invasive breast cancer
Treatment Options
Early Breast Cancer Trialists’ Collaborative Group (EBCTCG)
Clark M, et al. Lancet 2005
Analysis of data from 78 randomized controlled clinical trials (42K patients )
Results:
improved local control at 5 yrs resulted in improvement in DFS and OS at 15 yrs
strong causal link between local control and overall survival
Drug Therapy Management:
treatment of newly diagnosed breast cancer
treatment of recurrent breast cancer
treatment of refractory breast cancer
management of disease-related complications
prevention and management of therapy-related complicaitons
post-treatment complications
treatment of comorbidities
surviorship issues
Pharmacotherapy
Radiation
Surgery
resection of the cancer
Lymph node disection (LND)
radiation therapy is used after lumpectomy as adjuvant therapy
radiation is not used after mastectomy
course of radiation is given over weeks
Hormone therapy
Chemotherapy
Targeted therapy
Targeted therapy for angiogenesis
Single Agent:
anthracyclines:

doxorubicin or epirubicin
taxanes:

paclitaxel or docetaxel
cyclophosphamide
methotrexate
5 fluorouracil / capecitabine
gemcitabine
ixabepilone
Combination therapy:
CA
CA  T
CMF
TAC
Rationale:
some breast cancers are hormonal responsive
Early Stage Breast Cancer:
improved disease free survival (DFS) and overall survival (OS) with the use of hormonal therapy in adjuvant setting
Metastatic Breast Cancer:
disease regression in metastatic breast cancer with hormonal therapy
Strategy to decrease impact of estrogen:
interfere with estrogen
synthesis
interfere with estrogen
receptors

Selective estrogen receptor modulator (
SERM)
Tamoxifen
Toremifene
Raloxifene
Estrogen receptor antagonist
Fulvestrant
This strategy is effective for both
postmenopausal
and premenopausal woman
Strategy: interfere with estrogen receptor

interfere with estrogen synthesis

Premenopausal women :

estrogen production
ovaries
and
adrenal




Postmenopausal women:

estrogen production from
adrenal
Strategy to decrease impact of estrogen:
Strategy:
Blocking estrogen synthesis

in
premenopausal women
via ovarian ablation:
Surgical resection of ovaries (BSO)
LHRH agonist
chemotherapy
Suggestion that premenopausal women who cease to menstruate after adjuvant chemotherapy have  OS vs. those who continue to menstruate
LHRH vs ovarian ablation (surgery or radiation)
Meta analysis demonstrated benefit with ovarian ablation (surgery or radiation) compared to control patients.
Studies suggest similar benefit from ovarian suppression with LHRH agonist or antagonist to ovarian ablation.
Postmenopausal women:
aromatase inhibitor

(e.g. anastrazole, letrozole)
aromatase inactivator

(e.g. exemestane)
Strategy:
Aromatase Inhibitors:
MOA:
inhibit cytochrome P450 enzymes responsible for estrogen production through peripheral aromatization
SE:
hot flashes, mild nausea, headache, vaginal dryness, possible bone loss with long term use
Colorectal Cancer
Prostate cancer
Hormone receptors
are cytoplasmic proteins that transmit signals to the nucleus of the cell for growth and proliferation
- 50 – 70% women are hormone receptor +
- more common in postmenopausal women
Estrogen receptor (ER)
Progesterone receptor (PR)
Hormone receptors help predict response to hormone therapy
Monoclonal antibody
Trastuzumab (Herceptin)
Monoclonal antibody that binds to HER2neu
Given IV weekly (or q 3 week)
Side effects:
hypersensitivity (first dose)
cardiotoxicity
Resistance:
altered receptor antibody interaction
signaling through other growth factor receptors
decrease impact on downstream signals
Lapatinib:
Dual tyrosine kinase inhibitor:
HER2
EGFR
Small molecule that competes with ATP for binding sites on intracellular portion of HER1 and HER2
No cross resistance with trastuzumab
Current clinical application in patients who have had disease progression on trastuzumab therapy
May cross blood brain barrier
Daily oral dose
Targeted therapy for Her2/neu + cancers
Angiogenesis is important for tumor growth and metastases
Vascular endothelial growth factor (VEGF) is associated with angiogenesis in many cancers
Target for drug therapy for angiogenesis:
monoclonal antibody to VEGF
monoclonal antibody to VEGF
receptor
Tyrosine kinases
that work downstream the VEGF pathway
Bevacizumab
Monoclonal
antibody
against VEGF
Used in many cancers:
colorectal cancer
lung cancer
renal cell cancer
pancreatic cancer
glioma
breast cancer is
now controversial
Breast cancer: metastatic disease
- improvement in progression free survival
Toxicity:
hypertension, bleeding, thrombosis
High affinity binding to ER → downregulates ER
estrogen receptor antagonist
FDA labeled indication:
metastatic breast cancer, hormone receptor-positive, postmenopausal with disease progression following antiestrogen therapy
CONFIRM study demonstrated improvement PFS for dose fulvestrant
500mg
(vs 250mg)
Antiestrogen Therapy: Fulvestrant
Pharmacogenomics: Tamoxifen
4-hydroxy tamoxifen
is
100 x more potent
than the parent drug tamoxifen in suppressing
estrogen dependent cell growth
Allelic variations in CYP2D6 is an important determinant of tamoxifen’s activity
-anti-cancer action
-toxicity
shorter disease-free survival time in women who are
poor
metabolizers
Breast Cancer:
Hormonal Therapy
Ovarian Ablation in Premenopausal Women
Vasomotor Symptoms with
Antiestrogen Therapy
Women who take tamoxifen have been reported to have
night sweats
(>50%) and
hot flashes
(>75%)
Increased severity of vasomotor symptoms associated with
depression
and
insomnia
.
Classical management strategies
:
Hormone replacement therapy is contraindicated
Megesterol acetate
Transdermal clonidine
Selective serotonin reuptake inhibitor (SSRI)
(e.g. venlafaxine)
Acupuncture for Vasomotor Symptoms
Pilot studies indicate acupuncture treatment for 5 – 8 weeks ↓ vasomotor symptoms in ≈ 50% menopausal women
Randomized clinical trial : acupuncture vs placebo
Decreased in severity of hot flashes
No decrease in frequency of hot flashes
Randomized clinical trial: acupuncture to venlafaxine in individuals with hormone receptor positive breast cancer
Both groups - inc. hot flashes, dec. depressive symptoms
Both groups exhibited: improvements in mental health
Venlafaxine : inc. incidence of adverse effects from medication
Acupuncture: inc. sex drive, inc. energy, inc. sense of well-being.
Cancer Treatment
Induced Bone Loss
Management strategies

Monitoring of BMD
prior to initiation of therapy
DEXA scans yearly
Lifestyle management strategies
institute regular weight bearing exercise
avoid cigarette smoking
avoid chronic alcohol use
vitamin D and calcium
Prevention of CTIBL
Bisphophonate therapy
Denusomab
Bisphosphonate-Associated
Osteonecrosis
Management considerations:
Dental examination
for patient
prior
to initiation of bisphosphonate therapy
assessment of risk
procedures prior to therapy (e.g. extraction, restorative dentistry )
management of potential sites of infection
education for oral hygiene
Breast Cancer
and Surviorship
“ As advances in cancer medicine turn this once uniformly fatal illness into a curable disease for growing number and a chronic illness for many, understanding and meeting the needs of long-term cancer survivors and their caregivers has become a major public health challenge…”
Breast Cancer and Surviorship
Breast Cancer
and Survivorship
Quality of life (QOL) issues
physiological sequelae
psychological distress
social life distructions
Long term health effects of cancer and cancer treatment
Challenges in current literature:
_ cancer survivorship vs breast cancer survivorship _impact of non-cancer related issues
ethnic, cultural, socioeconomic background age
health, comorbidities
Late Effects of Breast Cancer Treatment: Menopause in Breast Cancer Survivors
Short-Term Effects:
vasomotor symptoms
vaginal effects
sexual health
body image
Long-Term Effects
osteoporosis
vaginal effects
cardiovascular disease
cognitive functioning
Breast Cancer
Disease related factors:
Stage (tumor, lymph nodes, metastatic disease)
Hormonal status
Histologic / nuclear grade
Proliferative rate
Lymphatic and vascular invasion
Her2/neu amplification / over expression
? markers of angiogenesis
genetic profile (Oncotype DX)
site of metastases
Treatment related factors:
Response to primary therapy
NOTE: there are prognostic tools to help evaluate treatment options (www.adjuvantonline.com)
An Overview of Prostate Cancer:Focus on Pharmacy Practice
Inc. incidence of prostate cancer since introduction of prostate specific antigen (PSA) but now has started to decline.
Dec. in death rates secondary to prostate cancer
Etiology
Hormonal:
testosterone growth signal to prostate
Inc. exposure to testosterone risk
Genetic:
Familial clustering
Prostatitic intraepithelial neoplasia (PIN):
Premalignant lesion proceeds prostate cancer
Age: median age diagnosis is 66 y/o (rare <40)
Gender : only occurs in male
Race: thought to be related to androgen receptors and testosterone production
Family History : increase risk in first degree relative
Diet : high fat diet may increase (?)
Occupation: exposure to industrial chemicals
Vasectomy: long term vasectomy (> 20 y/o) may increase risk
Risk Factors
Finasteride (5 alpha reductase inhibitor)
PCPT (prostate cancer prevention trial):
finasteride 5 mg po vs. placebo
 acute urinary retention
 need for surgery for symptomatic benign prostatic hyperplasia
 2.8% reduction of prostate cancer over 7 yrs.
treated patients had higher gleason score
Selenium
Lycopene
Prostate Specific Antigen (PSA)
PSA > 4 =>  evaluations
PSA > 10=>  suspicious for malignancy
PSA range increases with age
PSA velocity
% free PSA => <25% free PSA associated with prostate cancer
ScreeningFactors that Effect PSA
Increase:
Androgen receptor blockers
Ejaculation
Prostate manipulation
Prostate biopsy
Digital rectal exam
Decrease:
Finasteride (50% dec. )
Saw palmetto (unpredicatable)
Digital Rectal Examination (DRE)
Digital Rectal Examination (DRE)
Consistency of cancer vs normal tissue
Any changes in consistency  evaluated
Sensitivity 70 – 80%
Specificity 85 – 98%

Follow-up after abnormal PSA or DRE
Can use PSA density after TRUS
PSA / prostate volume as determined by TRUS
Transrectal
ultrsonography
(TRUS)
Digital Rectal Examination (DRE)
Prostate Specific Antigen (PSA)
Transrectal ultrsonography (TRUS)
Recommendation for screening:
men > 50 y/o be offered PSA screening with DRE by health care provider
men with < 10 yr life expectancy should not be routinely offered PSA
Screening
Prostate Specific Antigen
(PSA)
PSA is a glycoprotein produced by epithelial cells of prostate
Specific for prostate
Not specific for prostate cancer
Maybe effected by medications, etc.
Prevention
Assymptomatic with early disease
Advanced disease:
Changes in urination
Impotence
Lower extremity edema
Anemia
Weight loss
Pain
Signs and Symptoms
Natural History of Disease
Majority of prostate cancer are adenocarcinoma (99%)
Initial: indolent growth in prostate
Local extension: spread within the prostate capsule  beyond
Spread via lymph nodes and blood
Metastasizes to organs:
Bone, Liver, Lung
Diagnosis
Physical exam
PSA TRUS
Bone scan
Laboratories
Biospy of the prostate
- transurethral resection of the prostate (TURP)
GradingGleason Grade
Biopsy of the prostate
Score of 1 – 5 are assigned to the primary and secondary growth patterns  added together for Gleason score
Gleason score 1 – 4 : slow growing, well differentiated
Gleason scores 8 – 10 : poorly differentiated, aggressive
Note: The higher the score the greater the chance of extracapsular spread.
Staging
TNM system
T – confined to prostate / extends through prostatic capsule
N – regional lymph nodes
M – metastatic disease (bone vs other)
American Urological Society
A - D
Treatment Strategies
Surgery
Radiation Therapy
Pharmacotherapy
Hormonal therapy
Chemotherapy
Supportive care

Active Surveillance
observation, watchful waiting, expectant management or deferred treatment
active monitoring of patient and disease status with expectation to intervene if cancer progresses
appropriate candidates:
men with very low risk prostate cancer and life expectancy < 20 years
men with low risk prostate cancer and life expectancy < 10 years
Surgery
Resection of prostate
Hormonal manipulation with surgery

Surgery: radical prostatectomy
appropriate for patients whose tumor is clinically confined to the prostate
pelvic lymph node dissection (PLND)
side effects of radical prostatectomy
urinary incontinence
erectile dysfunction



Definition: long term incontinence defined as incontinence > 1 year
Risk factors
nerve resection
anastomotic stricture
age

Sexual Dysfunction
Erectile dysfunction (ED)
Orgasm difficulties
Difficulty reaching orgasm
Dry orgasm
Painful orgasm
Orgasm associated with urinary leak
Painful ejaculation
Changes in penis
Low sexual desire

Erectile Dysfunction: Management Strategies
Phosphodiesterase type- 5 inhibitors
Impact of therapy
efficacy seen post prostatectomy => increasing data to use early post operative
efficacy seen post radiation

Pharmacotherapy
Radiation Therapy
fewer side effects compared to surgery
improved targeting of radiation with emerging techniques decrease in side effects
Strategies:
External beam radiotherapy (30+ fractions)
Brachytherapy – placing radioactive sources into the prostate tissue
Proton therapy – clinical trials
Radiation Therapy
Surgery
Urinary incontinence
block with antiandrogens
Antiandrogens
Examples:
flutamide
,
bicalutamide,

nilutamide
Used as monotherapy and combination therapy (with LHRH or orchiectomy)
Used to reduce flare symptoms from LHRH
Dosing based on product:
flutamide
is dosed 3 x daily
bicalutamide
and nilutamide is dosed q day

Common side effects:
Diarrhea (most common with flutamide
)
Hematuria
Disulfiram reaction (
nilutamide
)
Hot flashes, decrease libido, impotence

weight gain
gynecomastia
loss of muscle mass, strength
decreased size of penis and testes
hair changes



median weight gain of 3 –6 kg over year ADT
difficult to loose weight post ADT
decrease in lean body mass
increase in total body fat (10 –20%)
management strategies
weight gain
Gynecomastia
breast tenderness
alteration in body image
management strategies: prophylactic radiation

Systemic
symptoms

fatigue
lack of energy
lack of initiative
aches and pains

Emotional
symptoms

depression
emotional liability
spatial memory

Metabolic/
physiologic

anemia
loss of BMD
bone mineral density

worsening
of comorbidities:

lipid disorder
hypertension
diabetes
heart disease

Prostate Cancer: Localized Disease
Treatment depends:
Stage
Grade
Patient’s age
Patient’s health
Patient’s preference
Options:
Close evaluation – watchful waiting
Radiation therapy
Surgery
Androgen ablation
Hormonal therapy
Surgery – not with metastatic disease
Radiation Therapy – palliation to bone disease
First line
Second line
Orchiectomy (removal of testes)
Immediate drop in testosterone levels
Relatively inexpensive
Side effects:
Impotence
Hot flashes
LHRH agonists
Examples
: leuprolide, gosrelin
Reversible method of androgen ablation
Dosage forms:
IM daily
IM depot q month
IM depot q 3 to 4 months
Common side effects:
flare-response
hot flashes
decrease libido
impotence
Focus is androgen deprivation
bicalutamide 50 mg po q day
Combined Androgen Blockade (CAB)
Strategy: LHRH + antiandrogen
CAB response is best in patients that are previously untreated
Some controversy if CAB is needed vs LHRH
CAB maybe more beneficial for improving survival in patients with minimal disease
CAB helps minimize tumor flare with LHRH
Common side effects:
Side effects from LHRH agonist
Side effects of antiandrogen
Mechanism of action
Irreversible inhibitor of CYP17
Inhibits androgen synthesis
Clinical trials:
- Patients with metastatic prostate cancer with disease progression after chemotherapy
Dose:
1000 mg po daily WITHOUT food
Given with prednisone
Side effects:
Fatigue, Nausea, Fluid retention, hypertension
Abiraterone Acetate
Androgen Deprivation Therapy (ADT)
Loss of libido
Erectile dysfunction
Hot flashes
Loss of libido ± erectile dysfunction
assessment of baseline sexual function
individuals have different interest levels
depressive symptoms associated with ED
application of ED treatments
relationship issues

incidence maybe as high as 75%
severity of hot flash ranges within population
impact on other symptoms  sleep

Androgen Deprivation Therapy (ADT)
Physical side effects
Treatment approaches:
progestational agents
estrogens
SSRI
gabapentin
Accupuncture
Complications:
osteopenia
osteoporosis
fracture
Inc. fracture starting 1 year post diagnosis
Strategies:
IV. bisphosphonates prevent bone loss due to ADT
oral bisphosphonate may prevent bone loss due to ADT

MOA:
reduction of bone resorption
interferes with osteoclast activation
Agents:
alendronate
clodronate
etidronate

Management of Advanced Prostate Cancer:
The Role of Bisphosphonates

skeleton is the most common site of recurrence of metastatic prostate cancer
manifestations of bone involvement range:
asymptomatic
hypercalcemia
pain
cord compression
fractures

ibandronate
pamidronate
risendronate
zolendronic acid

Bisphosphonates
Chemotherapy
Localized Disease
Treatment depends:
Stage
Grade
Patient’s age
Patient’s health
Patient’s preference
Options:

Options: Radiation therapy
Strategies:
external beam
brachytherapy
Radiation therapy = surgery
Options for patients not surgical options
Complications:
Impotence
Rectal symptoms
Bladder symptoms
Options: Surgery
Strategies:
Radical prostectomy (curative)
Radiation therapy = surgery
Benefit :
surgery => radiation
Complications:
Surgical complications
Bladder contraction
Incontinence
Impotence ( dec. incidence with nerve sparing)
Options: Androgen Ablation
Strategies:
LHRH  antiandrogen
Orchiectomy
Benefit
:
may be used in combination with RT
Complications:
Used in patients with high risk of recurrence

Options: Radiation therapy ± Neoadjuvant
hormonal therapy
Strategies:
Neoadjuvant hormonal therapy starts 2-3 months prior to radiation through radiation
Optimal duration not known
Rationale:
Radiation alone produces 5 yr survival 50 –60%
Neoadjuvant hormonal therapy improves DFS
Neoadjuvant hormonal therapy does not improve OS
Complications

Locally Advanced Disease
Metastatic Prostate Cancer
Options: Hormonal Therapy - first line
Strategies
:
CAB
LHRH
Rationale
Complications

Options: Hormonal Therapy - second line
Strategies:
Anti androgen withdrawal (20 – 30% response from androgen withdrawal)
Corticosteroids
- suppresses ACTH and adrenal angrogens
Aminoglutethimide
Ketoconazole
Megestol acetate

Abiraterone Acetate
Mechanism of action
Irreversible inhibitor of CYP17
Androgen synthesis inhibitor
Clinical trials:
- Patients with metastatic prostate cancer with disease progression after chemotherapy
Dose:
1000 mg po daily
Given with prednisone
Side effects:
Fatigue
Nausea
Fluid retention
hypertension

Close evaluation
watchful waiting

Castration Resistant Prostate Cancer
Ensure castration (testosterone< 50 ng/dl)
Antiandrogen → antiandrogen withdrawal
Asymptomatic disease: Sipuleucel T
Chemotherapy:
First line
Docetaxel + prednisone
Second line
Cabazitaxel
Abiraterone + prednisone
Ensure castration (testosterone< 50 ng/dl)
Antiandrogen → antiandrogen withdrawal
Asymptomatic disease: Sipuleucel T
Chemotherapy:
First line
Docetaxel + prednisone
Second line
Cabazitaxel
Abiraterone + prednisone (NOT CHEMOTHERAPY)
Sipuleucel-T (Provenge)
Active cellular immunotherapy- stimulates T-cell immunity against prostatic acid phosphatase
Preparation:
1.5- 2 blood volume mononuclear cell leukapheresis
Isolation of antigen presenting cells (APCs)
APCs cultured with fusion protein of PAP-GMCSF

Phase III Trials :
2 phase two trials in mCRPC with progressive diseaase
sipuleucel T infused over 30 minutes q 2 weeks x 3 treatment versus placebo
Time to progression (primary endpoint):
sipuleucel-T : 11.1 weeks
Placebo: 9.7 weeks
Median Survival:
sipuleucel-T : 23.2 months
Placebo: 18.9 months
Cerebrovascular events:
sipuleucel-T : 7.5 %
Placebo: 2.6 %

Phase III Trial in asymptomatic mCRPC (IMPACT) :
Patient s with antibody > 400 titers against PA2024 or PAP lived longer
Benefit mainly in asymptomatic , docetaxel-naïve disease
Overall survival different although TTP was not different

Options: Chemotherapy
Rationale:
All patients will become hormone refractory
Assess clinical benefit for treatment response
Strategies:
Docetaxel + prednisone ( survival)
Cabazitaxel + prednisone
Mitoxantrone + prednisone
Estramustine
paclitaxel

Castration-Recurrent Prostate Cancer
Cabazitaxel:
Mechanism of action:
Novel taxane with antitumor activity in paclitaxel and docetaxel restistant tumors
Dosing:
Cabazitaxel 25 mg/m2 q 3 weeks + prednisone 10 mg po daily
Side effects:
neutropenia
Anemia
Diarrhea
Peripheral neuropathy

http://www.youtube.com/watch?v=rQjddHhI-OQ&feature=related
Anthracylines:
Doxorubicin, Daunorubicin, Idarubicin
Mechanism of action:
intercalation into DNA  DNA strand breaks
topoisomerase inhibition
Side Effects:
bone marrow depression
mucositis
cardiac damage  cardiomyopathy
infertility and sterility
vesicant if drug is extravasated  cold
nausea / vomiting
alopecia
Asparaginase:
MOA:
enzyme that catalyzes the hydrolysis of asparagine (nonessential amino acid) to aspartic acid and ammonia
Toxicities:
- hypersensitivity reaction
- anorexia
-neurologic: HA, lethargy, depression, confusion, obtundation, coma, seizures (rare)
- rare BMD (transient)
- decrease albumin
- decrease fibrinogen
- decrease vitamin K dependent clotting factors
- decrease antithrombin III
- pancreatitis (5%)
(recommend keep > 100)
Full transcript