Oncology Pharmacotherapeutics

Reeves_Oncology Intro
Tuesday, February 02, 2016
9:32 AM
2/2/2016
Therapeutics 4 Page 1
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9:33 AM
- All cancers are different, but they

typically share these traits
- Benign tumors don't show local tissue
invasion & distant metastases
- New cases are a little different than deaths

- Prostate & breast cancer
- Know the top 4
Sxs, staging
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Cancer Screening
- A lot of the decreases in male cancer

is due to less smoking
- Colon cancer screening is most
beneficial. HPV & Pap tests are very
good for detecting Cervical. Varying
opinions overall on screening
- Thyroid cancer is typically curable
- Men death decreasing a little more
than women
- ~40% (or 1/3) people will develop
cancer. Men have higher chance,
mainly due to prostate cancer
- Over 1 million deaths avoid in 2013,
but cost was around 75 billion
- Signs vary widely

- Need to know if malignant or benign
(no need to do chemotherapy if
benign)
- Colon cancer shown

- Stage IV --> goes to other sites
- Hematologic cancers are staged differently
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9:33 AM
- Generally, a patient will have a tumor

for a long time before it is detected
- Body puts up an immunologic defense,
but tumor can eventually overcome
these
- Angiogenic switch - tumors get their
own nutrients
- Ideal to treat tumors early on when there
are fewer of them and they're growing
rapidly
- Surgery not recommended once cancer is

metastatic
- Radiation can be used after surgery if they
do not think they got all of the tumor
- Also good for treating certain symptoms
- Adjuvant therapy - an "insurance"

mechanism to make sure pieces of tumor
didn't metastasize elsewhere
Chemo Regimens
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- Want to give chemotherapy that will kill as

much of the tumor as possible
- Certain chemotherapies target specific areas
of the cell cycle
- Tumors can be resistant
- Allow hematologic recovery between

chemo doses (i.e. WBC count)
- Mostellar is more common equation

- Most cancer drugs are dosed using BSA
~ 1.84 m2
ADR's
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- Wrong drug or wrong route
- Chemotherapy can cause cancer; protect

employees
N/V
9:33 AM
- Nausea/vomiting is now treated better,

and is not on the patient's "top fear" list
- Less of a big deal than it used to

be, but still a problem
- How chemo causes N/V

Serotonin is main cause
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- Risk factors
- Cisplatin most often causes delayed N/V

Failing to control acute --> delayed
N/V
- Anxiety can play a role
- Breakthrough: N/V that occurs despite
adequate treatment
- Level 4 is highest risk

Doxorubicin /
cyclophosphamide
Prophylactic therapy
Dolasetron no longer recommended
Ondasetron is most commonly used
Granisetron comes as a patch - helps
w/ delayed N/V
- Palonsetron is a new drug
AE: Headache, increased LFTs, constipation,

QT prolongation
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9:33 AM
- Palonosetron vs. other drugs in

high emesis risk
- This study shows palonosetron is pretty

much equivalent to granisetron.
- The long term N/V benefits came from
adding a steroid
- Generally well tolerated

- Aprepitant & Fosaprepitant are most
common
Remember: interacts with
dexamethasone --> requires
dose adjustment
- Rolapitant is a new drug with fewer
drug interactions
- Dexamethasone is most
commonly used
AE - hyperglycemia, insomnia, dyspepsia, fluid retention, mood changes, weight gain
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9:33 AM
- Other options
- Biggest problem is
extrapyramidal effects
- Given on day of
chemotherapy
Highly emetic
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- Remember the dose reduction with

dexamethasone (exception is rolapitant)
- Olanzapine regimen possibly better at preventing
delayed N/V
- At risk for acute and delayed N/V

- Palonsetron has longer half-life
- *Prochlorperazine*
- Why we typically wait for 3-4 weeks

between doses
CSF's
9:33 AM
- G-CSF is Filgrastim (Neupogen)

- GM-CSF is rarely ever used
Sargramostim
- There are benefits to giving dose

dense regimens in certain cancers (i.e.
breast cancer)
- *Bone pain* is most common complaint

from filgrastim
- Pegfilgrastim is longer lasting - only for
pts with 2 weeks between chemo
regimens
- Many AE's with sargramostim
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9:33 AM
Colony stimulating factors
- To use or not to use is somewhat dependant upon

goals (i.e. curative vs. quality of life)
- Death risk is slightly lower

- But also risk of AML/MDS
- Not much evidence to use CSF drug

in these patients (i.e. come to the
hospital with febrile neutropenia)
- Anemia is common complication

- Risk increases with each cycle
Anemia
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Anemia, cont'd
- These drugs have risk of progressing tumors

and/or causing death
- Why they are only indicated for pts with
concomitant chemotherapy
Agent specific supportive care

9:33 AM
- Only for patients with goal of prolonging

survival (not for curing disease due to risk
of tumor progression)
- Both cyclo- and Ifosfamide are

prodrugs with extensive metabolism
- Cyclophosphamide can cause
secondary leukemias, and both can
cause secondary bladder cancer
- Daily "UA's"
^ antidote
*there is no prevention for the encephalopathy*
- Mesna binds to inactive metabolite
Platinum
9:33 AM
- One of the most toxic medications

(lots of N/V)
At risk for acute and
delayed N/V
- Ototoxicity can be permanent
(more of an issue with pediatric
patients)
- Use N/S for hydration - helps against toxicity

Mannitol may / may not help
- Hypersensitivity to carboplatin can occur after 7

courses (i.e. on 8th time they receive)
- Oxaliplatin neurotoxicity - acute is typically
reversible (typically triggered by cold); chronic
neuropathies are due to drug accumulation - can
take "drug holiday" --> can lead to fine motor
difficulties
Less N/V overall than carbo-
- Target AUC is a pre-defined goal
Use if obese
MTX
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Requires a lot of monitoring
Can form as a "depot" of the drug

Drugs that compete with MTX for elimination
- Nephrotoxicity is less likely when

pH is higher (wait until urine pH is
7 or above)
- Use oral dose unless you need to give

more than 25mg
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9:33 AM
FYI
-
- Actively break down MTX - accidental overdose,

or cannot eliminate the MTX (elevated SCr)
- Drug would get "preoccupied" with LV

instead of MTX
- Only give one dose

- Should quickly see decrease in MTX
Start 7 days before first dose of Pemetrexed
- Painful rash/peeling on hands and soles of feet
^ given to increase effect of drug in this instance
5-FU
9:33 AM
- BBW with warfarin

- See more mucositis and hand/foot
syndrome with this
- Rate limiting step
- Common choice for hematologic cancers
Anthracyclines
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- Typically give patient a basic neuro

exam before giving each higher dose
- Chemical conjunctivitis seen at high
doses (drug excreted in tears)
- Vesicant - can cause damage if

given outside of vein
Constant monitoring during
administration
- Dexrazoxane is a cardio-protectant; not

commonly given b/c it may also protect
cancer cells
- Baseline ejection fraction
CHF chance goes up starting ~ 450

There is a lifetime cap for these drugs
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9:33 AM
"I run to the can"
^ patients can be hypersensitive to polysorbate 80
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9:33 AM
- Vincristine is most neurotoxic

- Fatal if given intrathecally (all of
them)
- Overall, similar to paclitaxel
- Prostate cancer
- Lots of diarrhea (even fatal)
Targeted Tx
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"Newer" drugs
Increased risk of ADR's if chimeric

(xi) or mouse (o)
Disrupt the tumor's

attempt to gain its
own blood supply
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9:33 AM
- Hyperglycemia, hyperTG,
hypercholesterolemia
^ benadryl
Having some skin

rash is fine (it is
associated with
better patient
response)
Similar ADR's
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9:33 AM
- Less rash
- More cardiotoxicity
Typically
cycled with
anthracyclines
(two meds that
can cause
cardiotoxicity)
Autoimmune type
reactions b/c they allow
immune system to
attack
- Edema,
hepatotoxicty,
myelosuppression are
common ADR's
Used in patients
with CML
AE management
9:33 AM
(stem cell transplant)
- We don't have very good

prevention or treatment
measures : /
Ice cubes in mouth can limit drug effects
- Not used commonly
(hand-foot syndrome)
- Want to see some acniform rash b/c

associated with better response to tx
- Still occurs, just less severe
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9:33 AM
- Extravasation (drug mistakenly

does not go into vein)
- Prefer IV push (nurse is there
the entire time)
Emergencies
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Tumor presses on spinal cord

Tumor presses on superior vena cava
- Generally want to see tumor lysis syndrome
- Butdon't want to see body's inability to break
down tumor components
- Main problems are electrolyte related
DNA from tumors
- Leukemias are typically high risk

- Bulky disease = bigger tumors =
higher risk
Lab values that tell when

patient is in tumor lysis
syndrome
- Manage electrolyte
abnormalities as they
come up
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9:33 AM
- Prevent xanthine from being formed with

allopurinol
- Break down existing uric acid with rasburicase
(Kayexalate)
Page 30
9:33 AM
- Rasburicase is very expensive; typically

don't use it unless you have to
- Rasburicase breaks down current uric acid
but doesn't do anything for future uric
acid (why allopurinol also used)
- Just a one-time dose of rasburicase
- Secretion of protein (similar to PTH)

by the cancer
And mental status changes
Page 31
9:33 AM
- Bisphosphonates can cause renal

dysfunction

Oncology Pharmacotherapeutics

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Reeves_Oncology Intro

Tuesday, February 02, 2016

- All cancers are different, but they

- New cases are a little different than deaths

- A lot of the decreases in male cancer

- Signs vary widely

- Colon cancer shown

- Generally, a patient will have a tumor

- Surgery not recommended once cancer is

- Adjuvant therapy - an "insurance"

- Want to give chemotherapy that will kill as

- Tumors can be resistant

- Allow hematologic recovery between

- Mostellar is more common equation

- Wrong drug or wrong route

- Chemotherapy can cause cancer; protect

- Nausea/vomiting is now treated better,

- Less of a big deal than it used to

- How chemo causes N/V

- Cisplatin most often causes delayed N/V

- Level 4 is highest risk

AE: Headache, increased LFTs, constipation,

- Palonosetron vs. other drugs in

- This study shows palonosetron is pretty

- Generally well tolerated

AE - hyperglycemia, insomnia, dyspepsia, fluid retention, mood changes, weight gain

- Remember the dose reduction with

- At risk for acute and delayed N/V

- Why we typically wait for 3-4 weeks

- G-CSF is Filgrastim (Neupogen)

- There are benefits to giving dose

- *Bone pain* is most common complaint

- Many AE's with sargramostim

Colony stimulating factors

- To use or not to use is somewhat dependant upon

- Death risk is slightly lower

- Not much evidence to use CSF drug

- Anemia is common complication

- These drugs have risk of progressing tumors

Agent specific supportive care

- Only for patients with goal of prolonging

- Both cyclo- and Ifosfamide are

- Mesna binds to inactive metabolite

- One of the most toxic medications

- Use N/S for hydration - helps against toxicity

- Hypersensitivity to carboplatin can occur after 7

- Target AUC is a pre-defined goal

Requires a lot of monitoring

Can form as a "depot" of the drug

- Nephrotoxicity is less likely when

- Use oral dose unless you need to give

- Actively break down MTX - accidental overdose,

- Drug would get "preoccupied" with LV

- Only give one dose

Start 7 days before first dose of Pemetrexed

- Painful rash/peeling on hands and soles of feet

^ given to increase effect of drug in this instance

- BBW with warfarin

- Rate limiting step

- Common choice for hematologic cancers

- Typically give patient a basic neuro

- Vesicant - can cause damage if

- Dexrazoxane is a cardio-protectant; not

CHF chance goes up starting ~ 450

- Bone pain is most common complaint