Antineoplastics Drugs
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Transcript of Antineoplastics Drugs
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Common Chemotherapy Agents
Agent Mechanism Genetic Issues Side Effects Renal/Hepatic Dosage
Adjustment
Comments
Dacarbazine (DTIC) Alkylation of DNA
leading to inhibition of
DNA, RNA, and protein
synthesis
None Myelosuppression; Severe
nausea and vomiting; Flu-like
syndrome starting a week after
treatment and lasting 1 to 3
weeks
CrCl 46-60 mL/min:
decrease dose by 20%; CrCl
31-45 mL/min: decrease
dose by 25%; CrCl 2 mg/dL or bilirubin
>3 mg/dL: decrease the
dose; SCr >5 mg/dL ortransaminases >3xULN:
consider avoiding
Monoamine oxidase inhibitor -
tyramine-rich foods must be
avoided; Disulfiram-likereaction with alcohol
Thiotepa Cross-link DNA None Myelosuppression; Nausea and
vomiting; Venous irritation
Reduced dose may be
necessary for patients withrenal impairment
May be used intrathecally
Altretamine
(Hexalen)
Cross-links DNA None Less prominent
myelosuppression; Nausea;Encephalopathy (confusion,
lethargy, psychosis); Moodswings; Neuropathy
Barbiturates increases
metabolism; Cimetidine inhibitsmetabolism
Melphalan (Alkeran) Cross-link DNA None Myelosuppression; Nausea and
vomiting; Pulmonary toxicity
not dose related; Anorexia;
Diarrhea; Neuropathy; Agitation;
Confusion
CrCl 10-50 mL/: decrease
dose 25%;
CrCl
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Common Chemotherapy Agents
Agent Mechanism Genetic Issues Side Effects Renal/Hepatic Dosage
Adjustment
Comments
Angiogenesis Inhibitors
Bevacizumab
(Avastin)
Recombinant humanized
MoAb directed against
VEGF that prevents
neoangiogenesis
None Hypertension responds to
antihypertensive agents;
Bleeding transient nose bleeds
most common, but fatal CNSand GI bleeds can occur;
Thrombosis deep veinthrombosis, pulmonaryembolism, heart attack;
Proteinuria; GI perforation
Used in combination with
traditional chemotherapeutic
agents; Counsel patients to
report abdominal painimmediately; Check urine
protein if 2+ or more bydipstick bevacizumab may not
be safe to administer; Use
caution when used before or
after surgery due to risk of
wound healing complications
Anthracyclines
Daunorubicin(Cerubidine)
Daunorubicin
liposomal(DaunoXome)
Intercalate with DNA andinhibit RNA synthesis;
Topoisomerase II
inhibitor
None Myelosuppression;Cardiotoxicity; Frequently
causes alopecia; Mucositis; Mild
to moderate nausea and
vomiting; Red urine
Bilirubin >3 mg/dL:decrease dose by 50%;
Bilirubin >5 mg/dL: avoid;
SCr >3 mg/dL: decreasedose by 50%
Vesicant; Extravasation cancause significant injury; Avoid
cumulative doses over 400 to
600 mg/m2
to avoid risk of
cardiomyopathy;Acetaminophen and BCNU
increase liver toxicity
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Common Chemotherapy Agents
Agent Mechanism Genetic Issues Side Effects Renal/Hepatic Dosage
Adjustment
Comments
Aldesleukin (IL-2,
Proleukin)
Stimulates the
development of cytoxic
cells that recognize and
destroy tumor cells
None Dose-related hypotension, fluid
retention, and kidney
dysfunction especially in
patients with cardiac or kidney
problems; Thrombocytopenia;Anemia; Eosinophilia;Reversible cholestasis; Skin
redness with burning and itching
Vasopressor, fluids, and
diuretic support often needed
due to vascular leak syndrome;
Acetaminophen for fever;
Severe rigor and chills mayrequire meperidine; Skinredness and itching may
respond to oral antihistamines
avoid all steroids including
topicals
Denileukin (Ontak) Recombinant fusion
protein combining active
portions of IL-2 and
diphtheria toxin thatinhibits protein synthesis
and causes cell death
None Acute hypersensitivity reactions
hypotension, vasodilation,
rash, chest tightness; Flu-like
symptoms; Diarrhea; Vascular-leak syndrome (delayed onset
and usually self-limited); Nausea
and vomiting; Asthenia;Hepatotoxicity
Slow the rate or interrupt the
infusion for hypersensitivity
reactions and treat with a
steroid, antihistamine, andacetaminophen
Inhibitors of EGFR Receptors
Cetuximab (Erbitux) Recombinant chimericMoAb that binds to
endothelial growth factor
receptor (EGFR) causinginhibition of cell growth
and vascular endothelial
growth factor (VEGF)
production and increased
programmed cellular
death (apoptosis)
EGFR mutation maypredict benefit;KRASmutation predicts lack
of benefit; ConsiderBRAF testing if
BRAF mutation is
present may predict
lack of response
Severe infusion reactions airway obstruction and
hypotension; Acne-like rash on
face upper chest, and backwithin the first 2 weeks of
therapy; Fatigue; GI effects
nausea, vomiting, diarrhea,
constipation, abdominal pain;
Hypomagnesemia;
Hypersensitivity reactions; Fever
Use diphenhydramine prior toadministration
Panitumumab
(Vectibix)
Recombinant human IgG2
MoAb that binds to the
epidermal growth factor
receptor inhibiting cellsurvival, growth, and
proliferation
EGFR mutation may
predict benefit;Notrecommended to use
with KRAS mutation;Consider BRAF testing
if BRAF mutation is
present may predict
lack of response
Dermatologic toxicities common
(acne-like lesions, itching,
redness, rash, skin exfoliation,
etc); Diarrhea
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Common Chemotherapy Agents
Agent Mechanism Genetic Issues Side Effects Renal/Hepatic Dosage
Adjustment
Comments
L-Asparaginase
(Elspar)
Deaminates asparagines
and inhibits protein
synthesis
None Hepatotoxicity; Encephalopathy
(lethargy and confusion);
Occasional cerebral dysfunction
(stupor, coma, disorientation,
hallucinations); Pancreatitis;Hyperglycemia; Hypersensitivityreactions
Test dose prior to the first dose
or when restarting therapy after
7 days or more; Inhibits
synthesis of fibrinogen and
other coagulation factors andcan result in an increased INR,PTT, and bleeding
complications; Blocks the
action of methotrexate; With
allergic reactions use
pegaspargase instead
Arsenic trioxide
(Trisenox)
Metabolized to arsenic
that damages genes in
leukemic cells
None Prolongation of QT interval;
Peripheral neuropathy;
Musculoskeletal pain; Dry skin;Hyperglycemia; APL
differentiation syndrome:
pulmonary dysfunction, pleuralor pericardial effusion
Use with caution in renal
dysfunction, but effects in
renal or hepatic dysfunctionare unknown
ECG twice a week during
dosing; Avoid other QT
prolonging drugs; Monitor andreplace potassium and
magnesium as needed
Mitomycin C(Mutamycin)
Cross-link DNA None Delayed myelosuppression;Pulmonary toxicity; Hemolytic
uremic syndrome; Cardiac
toxicity; Pulmonary toxicity
CrCl 1.5x
ULN: decrease dose to 0.7
mg/m2
Temsirolimus(Torisel)
Binds to FKBP-12 andinhibits the activity of
mammalian target ofrapamycin (mTOR)
resulting in inhibition of
protein synthesis and
angiogenesis
None Rash; Fatigue; Mucositis;Nausea; Edema; Loss of
appetite; Increases in creatinineand liver function tests;
Thrombocytopenia;
Neutropenia; Hyperglycemia;
Hyperlipidemia; Rash; Shingles
Monitor blood glucose andlipids; Affected by CYP3A4
inhibitors and inducers
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Common Chemotherapy Agents
Agent Mechanism Genetic Issues Side Effects Renal/Hepatic Dosage
Adjustment
Comments
Monoclonal Antibodies
Rituximab (Rituxan) Chimeric MoAb directed
against the CD20 antigen
on normal and malignant
B-cells that causes B-celllysis
Malignancies with
CD20-antigen
expression
Hypersensitivity reactions
(fever, chills, nausea, asthenia,
headache); Tumor lysis;
Neutropenia, thrombocytopenia,and anemia are relatively rare;
Progressive multifocalencephalopathy
Use diphehydramine and
acetaminophen prior to
administration; Severe infusion
reaction are most likely duringthe first infusion
Ibritumomab
(Zevalin)
Murine anti-CD20 MoAb
to which indium-111
(imaging and dosimetry)
or yttrium-90
(radiotherapy) are
attached causing radiationinduced cell death
Malignancies with
CD20-antigen
expression
Infusion reactions including life-
threatening anaphylaxis with
greatest risk during the first
infusion of rituximab; Prolonged
thrombocytopenia and
neutropenia are common
Use diphenhydramine and
acetaminophen prior to
administration; Regimen
involved administration of
rituximab to decrease B-cells,
then In-111 ibritumomab fordosimetry (calculating the
necessary radiation dose) and
imaging, then a second dose of
rituximab followed by Y-90
ibritumomab to deliverradiation directly to cells
expressing the CD20 antigen
Tositumomab
(Bexxar)
Murine anti-CD20 MoAb
that can be linked to I-131to cause radiation induced
cell death
Malignancies with
CD20-antigenexpression
Similar to ibritumomab Renal dysfunction may
delay elimination ofI-131
Use diphenhydramine and
acetaminophen prior toadministration; Thyroid is
protected by pre-administration
of SSKI 4 drops TID starting at
least 24 hours in advance of I-
131 tositumomab and continued
for 14 days; Regimen involvesnaked tositumomab first to
lower B-cell count followed by
I-131 labeled tositumomab at a
lower dose for imaging anddosimetry, then a larger dose if
I-131 labeled tositumomab is
given to deliver radiation
directly to cells expressing the
CD20 antigen
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Common Chemotherapy Agents
Agent Mechanism Genetic Issues Side Effects Renal/Hepatic Dosage
Adjustment
Comments
Azacitidine (5AZC,
Vidaza)
Not completely
understood; Inhibits DNA
methyltransferase
insertion into DNA;
Promoteshypomethylation of DNAnormalizing cells that
control cell differentiation
None Myelosuppression; Renal tubular
acidosis; Renal dysfunction;
Injection-site reactions; Nausea
and vomiting with high doses
Renally excreted, so some
experts suggest delaying the
next cycle and reducing
dose by 50% if increases in
BUN/SCr occur
Decitabine
(Dacogen)
Not completely
understood; Inhibits DNA
methyltransferase
insertion into DNA;
Promotes
hypomethylation of DNAnormalizing cells that
control cell differentiation
None Myelosuppression; Injection-site
reactions with non-IV dosing
Hold for SCr >2 mg/dL or
ALT/Bilirubin >2xULN
Taxanes
Paclitaxel (Taxol)
Paclitaxel albumin-bound (Abraxane)
Inhibit function ofmicrotubules; Inhibition
of angiogenesis
None Myelosuppression;Neurotoxicity (glove and
stocking numbness);Bradycardia; Hypersensitivity
reactions (less of a problem with
the albumin bound product) ;
Frequently causes alopecia;
Cardiac conduction disturbances;
Nausea is infrequent
24-hour infusion:Transaminases
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Common Chemotherapy Agents
Agent Mechanism Genetic Issues Side Effects Renal/Hepatic Dosage
Adjustment
Comments
Docetaxel
(Taxotere)
Inhibit function of
microtubules; Inhibition
of angiogenesis
None Myelosuppression; Stomatitis;
Fluid retention; Frequently
causes alopecia; Neurotoxicity
(numbness); Hypersensitivity
reactions
Bilirubin > ULN or
transaminases >1.5xULN
with alkaline phosphatase
>2.5xULN: contraindicated
Premedicate with
dexamethasone 8 mg BID for 3-
5 days starting the day before
treatment to prevent fluid
retention and hypersensitivityreactions; Administer beforecisplatin to avoid reduced
clearance of docetaxel; Lower
the dose of gemcitabine when
administered concurrently;
Lower warfarin dose and
monitor INR when usedconcurrently
Topoisomerase InhibitorsEtoposide (VePesid,
VP-16)
Damage DNA and
prevent repair;
Topoisomerase II
inhibitor
None Myelosuppression;
Neurotoxicity (numbness)
Hepatotoxicity with high dose;
Alopecia; Nausea and vomiting;
Hypotension-fever-asthmaticepisode after infusion; Mucositis
CrCl 10-50 mL/min:
decrease dose by 25%;
CrCl 180 units: decrease
dose by 75%;
Bilirubin >5 mg/mL: Dontadminister
Teniposide (Vumon) Damage DNA and
prevent repair;
Topoisomerase I inhibitor
None Myelosuppression;
Neurotoxicity (numbness)
Hepatotoxicity with high dose;
Alopecia; Nausea and vomiting;Hypotension-fever-asthmatic
episode after infusion; Mucositis
Dose adjustment may be
necessary for renal or
hepatic dysfunction
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C Ch th A t
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Common Chemotherapy Agents
Agent Mechanism Genetic Issues Side Effects Renal/Hepatic Dosage
Adjustment
Comments
Imatinib (Gleevec) Selective inhibitor of
BCR-Abl tyrosine kinase
resulting in prevention of
cell proliferation,
apoptosis, and arrest ofgrowth in cells expressingBCR-Abl mutation (aka
Philadelphia
chromosome); also
inhibits mutated c-KIT
and PDGF
BCR-ABL testing for
Philadelphia
chromosome-positive
(Ph+) leukemia and c-
KIT expression forc-KIT (CD117)-positivetumors; T315I
mutations can decrease
response
Myelosuppression; Mild to
moderate edema, but severe fluid
retention can occur; Liver
function test elevation; Nausea;
Muscle cramps; Headache; Rash(rare Stevens-Johnsonssyndrome requiring permanently
stopping therapy)
Effect of hepatic or renal
impairment unknown
Able to eliminate the
Philadelphia chromosome
genetic defect; Monitor for
swelling of legs, feet, or
shortness of breath; Affected by3A4 inhibitors and inducers
Dasatinib (Sprycel) Same as imatinib but
retains activity in imatinib
resistant cases; InhibitsSrc kinase
BCR-ABL testing for
Philadelphia
chromosome-positive(Ph+) leukemia
Similar to above Indicated for leukemia resistant
to imatinib; Monitor for
swelling of legs, feet, orshortness of breath; Affected by
3A4 inhibitors and inducers
Nilotinib (Tasigna) Same as imatinib but
retains activity in imatinib
resistant cases
BCR-ABL testing for
Philadelphia
chromosome-positive(Ph+) leukemia;
UGT1A1*28 predicted
increases in bilirubin
Myelosuppression; Rash;
Pruritus; Nausea; Fatigue;
Headache; Constipation;Diarrhea; Vomiting; QT
prolongation
Indicated for leukemia resistant
to imatinib; Inhibitor of
CYP2C8, CYP2C9, andCYP2D6
Sunitinib (Sutent) Inhibitor of tyrosine
kinase, VEGFR-2, platelet
derived growth factor
receptor, c-KIT (GI
stromal tumors), and
FLT3 (leukemia)
None Diarrhea; Rash; Fatigue;
Hypertension; Congestive heart
failure; Neutropenia;
Hyperpigmentation;
Hepatotoxicity; Palmar-plantar
dysesthesias or hand-foot
syndrome (redness, tenderness,blistering of palms and soles of
the feet); Bleeding; Yellow skin
with dryness and cracking; Hair
may depigment with doses over50 mg/day
Affected by 3A4 inhibitors and
inducers
Sorafenib (Nexavar) Similar to above, plus
inhibits serine/threonine
kinase Raf which isinvolved in cell
proliferation
None Diarrhea; Rash; Fatigue;
Hypertension; Palmar-plantar
dysesthesias or hand-footsyndrome (redness, tenderness,
blistering of palms and soles of
the feet)
C Ch th A t
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Common Chemotherapy Agents
Agent Mechanism Genetic Issues Side Effects Renal/Hepatic Dosage
Adjustment
Comments
Vinca Alkaloids
Vincristine
(Vincasar PFS,
Oncovin)
Inhibit function of
microtubules
None Mild myelosuppression;
Neurotoxicity (paresthesias,
depression of reflexes,
stumbling, falling); Loss ofreflexes common with
cumulative doses over 6 to 8 mg;Cranial nerve toxicity (lid lag,facial palsy, trigeminal
neuralgia); Constipation; SIADH
Bilirubin 1.5-3.0 mg/dL or
AST 60-180 units: decrease
dose by 50%; Bilirubin 3-5
mg/dL: decrease dose by75%;
Bilirubin >5 mg/dL or AST>180 units: avoid use
Vesicant; Fatal if given
intrathecally; Stimulant
laxatives (senna, bisacodyl) +/-
stool softener prophylacticallyto prevent constipation; Some
cap the total dose at 2 mg toavoid neuropathic side effects;Affected by CYP 3A4
inhibitors or inducers (for
example, itraconazole can cause
severe neurotoxicity when
administered concurrently)
Vinblastine (Velban) Inhibit function ofmicrotubules
None Dose limiting myelosuppression;Neurotoxicity less than
vincristine (paresthesias,
depression of reflexes,
stumbling, falling); Cranial
nerve toxicity (lid lag, facialpalsy, trigeminal neuralgia);
Constipation; Pulmonary
toxicity in combo with
mitomycin; Rash; Stomatitis
Bilirubin 1.5-3.0 mg/dL orAST 60-180 units: decrease
dose by 50%; Bilirubin 3-5
mg/dL: decrease dose by
75%;
Bilirubin >5 mg/dL or AST>180 units: avoid use
Vesicant; Fatal if givenintrathecally; Affected by CYP
3A4 inhibitors or inducers
Vinorelbine
(Navelbine)
Inhibit function of
microtubules
None Dose limiting myelosuppression;
Dyspnea/cough; Neurotoxicity
(paresthesias, depression of
reflexes, stumbling, falling);
Cranial nerve toxicity (lid lag,
facial palsy, trigeminalneuralgia)
Bilirubin >2.1-3.0 mg/dL:
decrease dose by 50%;
Bilirubin >3 mg/dL:
decrease dose by 75%
Vesicant; Fatal if given
intrathecally; Affected by CYP
3A4 inhibitors or inducers
APL = acute promyelocytic leukemia
CrCl = creatinine clearance
PCP = Pneumocystis pneumoniaSCr = serum creatinine
SIADH = syndrome of inappropriate antidiuretic hormone
ULN = upper limit of normal