Antineoplastics Drugs

8/6/2019 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


3/17



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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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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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


9/17



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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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


14/17



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


15/17

C Ch th A t


16/17



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


17/17



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

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Antineoplastics Drugs