Chemo Meds

Common Chemotherapy Agents

Agent Mechanism Genetic Issues Side Effects Renal/Hepatic Dosage Adjustment

Comments

Alkylating AgentsCyclophosphamide (Cytoxan)

Cross-link DNA None Myelosuppression; Hemorrhagic cystitis; Frequently causes alopecia; Pulmonary toxicity (not dose related); Cardiotoxic at high doses; Delayed nausea and vomiting; SIADH with doses over 50 mg/kg

CrCl <10 mL/min: decrease dose by 25%; Bilirubin 3.1-5 mg/dL or transaminases >3xULN: decrease dose 25%

With doses over 1200 mg/m2 hydration and mesna (Mesnex) at 60-80% of the Cytoxan dose to protect against hemorrhagic cystitis; Consider mesna with doses over 750 mg/m2

Chlorambucil (Leukeran)

Cross-link DNA None Myelosuppression; Alopecia; Pulmonary toxicity (after at least 6 mo. of treatment with a total cumulative dose >2 g)

CrCl 10-50 mL/min: decrease dose by 25%;CrCl <10 mL/min: decrease dose by 50%;Dosage adjustment may be necessary with hepatic dysfunction

Busulfan (Myleran, Busulfex)

Cross-link DNA Philadelphia (Ph1) chromosome absence predicts poor leukemia response

Prolonged myelosuppression; Hyperpigmentation; Pulmonary toxicity; Severe nausea and vomiting, seizures, and sinusoidal obstruction syndrome with high doses

Dosage adjustment may be needed with hepatic dysfunction

Anticonvulsant prophylaxis for patients receiving high doses

Ifosfamide (Ifex) Cross-link DNA None Myelosuppression; Hemorrhagic cystitis; Frequently causes alopecia; Encephalopathy (confusion, lethargy, psychosis); Cranial nerve toxicity (lid lag, facial palsy, trigeminal neuralgia)

CrCl <10 mL/min: decrease dose by 25%

Guidelines recommend mesna (Mesnex) at 60% of the ifosfamide dose at zero, 4, and 8 hours after ifosfamide to avoid cystitis – other regimens include an equal mg dose

Carmustine (BiCNU, Gliadel)

Cross-link DNA None Delayed myelosuppression; Severe nausea and vomiting; Hepatotoxic and nephrotoxic at high doses; High doses can cause encephalopathy (confusion, seizures); Pulmonary toxicity (doses >1,400 mg/m2)

CrCl 46-60 mL/min: decrease dose by 20%; CrCl 31-45 mL/min: decrease dose by 25%; CrCl <30 mL/min: avoid use

Gliadel Wafer for brain tumors; Placed in tumor cavity after tumor removal and allowed to dissolve over 3 weeks

Lomustine (CeeNU) Cross-link DNA None Delayed myelosuppression; Pulmonary toxicity; Nephrotoxic at high doses

CrCl 10-50 mL/min: decrease dose by 25%; CrCl <10 mL/min: decrease dose by 50-75%

Administration at bedtime with an antiemetic lowers the risk and severity of nausea; Usually single oral dose per cycle



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 <30 mL/min: decrease dose by 30%

Doesn’t cross the blood-brain barrier

Temozolomide (Temodar)

Alkylation of DNA leading to inhibition of DNA, RNA, and protein synthesis

Increased sensitivity with MGMT promoter methylation

Myelosuppression; Nausea and vomiting; Headache; Fatigue; Constipation; Immunosuppressive with continuous dosing

Dosage adjustments may be needed with moderate to severe renal or hepatic dysfunction

Crosses the blood-brain barrier well; Minimize nausea by giving the dose at bedtime

Procarbazine (Matulane)

Alkylation of DNA leading to inhibition of DNA, RNA, and protein synthesis

None Myelosuppression; Nausea and vomiting; Flu-like syndrome; Encephalopathy (confusion, lethargy, psychosis); Pulmonary toxicity

SCr >2 mg/dL or bilirubin >3 mg/dL: decrease the dose; SCr >5 mg/dL or transaminases >3xULN: consider avoiding

Monoamine oxidase inhibitor - tyramine-rich foods must be avoided; Disulfiram-like reaction with alcohol

Thiotepa Cross-link DNA None Myelosuppression; Nausea and vomiting; Venous irritation

Reduced dose may be necessary for patients with renal impairment

May be used intrathecally

Altretamine (Hexalen)

Cross-links DNA None Less prominent myelosuppression; Nausea; Encephalopathy (confusion, lethargy, psychosis); Mood swings; Neuropathy

Barbiturates increases metabolism; Cimetidine inhibits metabolism

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 <10 mL/min: decrease dose by 50%

Mechlorethamine (Mustargen)

Cross-link DNA None Myelosuppression; Nausea and vomiting

Vesicant; Can cause patients to become sterile; Can be prepared into an ointment; Unused vials should be neutralized with 5% sodium thiosulfate and 5% sodium bicarbonate



Comments

Angiogenesis InhibitorsBevacizumab (Avastin)

Recombinant humanized MoAb directed against VEGF that prevents neoangiogenesis

None Hypertension – responds to antihypertensive agents; Bleeding – transient nose bleeds most common, but fatal CNS and GI bleeds can occur; Thrombosis – deep vein thrombosis, pulmonary embolism, heart attack; Proteinuria; GI perforation

Used in combination with traditional chemotherapeutic agents; Counsel patients to report abdominal pain immediately; Check urine protein – if 2+ or more by dipstick bevacizumab may not be safe to administer; Use caution when used before or after surgery due to risk of wound healing complications

AnthracyclinesDaunorubicin (Cerubidine)

Daunorubicin liposomal (DaunoXome)

Intercalate with DNA and inhibit 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: decrease dose by 50%

Vesicant; Extravasation can cause significant injury; Avoid cumulative doses over 400 to 600 mg/m2 to avoid risk of cardiomyopathy; Acetaminophen and BCNU increase liver toxicity



Comments

Doxorubicin (Adriamycin)

Doxorubicin liposomal (Doxil)


HER2 breast cancers are often sensitive to anthracyclines

Myelosuppression; Cardiotoxicity (liposomal may be less cardiotoxic); Arrhythmias; Frequently causes alopecia; Palmar-plantar dysesthesias or hand-foot syndrome (redness, tenderness, blistering of palms and soles of the feet); Mucositis; Hyperpigmentation; Nausea and vomiting; Red urine

Bilirubin >3 mg/dL: decrease dose by 75%Bilirubin >1.5 mg/dL: decrease dose by 50%

Vesicant; Extravasation can cause significant injury; To avoid significant risk of cardiomyopathy give no more than a total cumulative dose of 450 mg/m2 in patients with one or more cardiac risk factors and no more than 550 mg/m2 in those without risk factors; Radionuclide ventriculography (RNV) or MUGA scans or echocardiograms recommended to check cardiac function at baseline, if signs of failure appear, when dose reaches 400 mg/m2 and again at 500 mg/m2, and with every additional 50 mg/m2 dose; When given with paclitaxel, separate doses by 24 hours to avoid enhanced doxorubicin exposure; To avoid cardiac toxicity, consider dexrazoxane (Zinecard) when cumulative dose exceeds 300 mg/m2; Acetaminophen and BCNU increase liver toxicity

Epirubicin (Ellence) Intercalate with DNA and inhibit RNA synthesis; Topoisomerase II inhibitor


Myelosuppression; Cardiotoxicity; Frequently causes alopecia; Hyperpigmentation; Red urine; Nausea and vomiting

Bilirubin >1.2-3 mg/dL or AST 2-4xULN: decrease dose by 50%Bilirubin >3 mg/dL or AST >4xULN: decrease dose by 75%; SCr >5 mg/dL: consider dose decrease or avoid

Vesicant; Extravasation can cause significant injury; Avoid a total cumulative dose of >900 mg/m2 due to risk of cardiomyopathy; Cimetidine can significantly increase exposure

Idarubicin (Idamycin)



Myelosuppression; Cardiotoxicity; Mucositis; Red urine; Mild to moderate nausea and vomiting

Bilirubin >5 mg/dL: avoid use; Consider dose reductions for bilirubins lower than this (no published guidelines)

Vesicant; Extravasation can cause significant injury; Avoid cumulative dose >150 mg/m2 to avoid significant risk of cardiomyopathy



Comments

Mitoxantrone (Novantrone)

Not technically an anthracycline but often listed with them; Intercalate with DNA and inhibit RNA synthesis; Topoisomerase II inhibitor


Myelosuppression; Cardiotoxicity (less than doxorubicin); Blue urine, sclerae, and nails; Nausea and vomiting

Consider dose reduction with hepatic dysfunction (no published guidelines)

Less extravasation injury; Avoid a total cumulative dose of >160 mg/m2 or >100 mg/m2 with previous doxorubicin due to risk of cardiomyopathy

AntifolatesMethotrexate (MTX)

Prevents DNA synthesis None Myelosuppression; High dose IV occasionally causes encephalopathy; Palmar-plantar dysesthesias or hand-foot syndrome (redness, tenderness, blistering of palms and soles of the feet); Mucositis; Intrathecal use can cause chemical meningitis; Nephrotoxicity with high doses; Pulmonary toxicity (not dose related); Hepatotoxicity with daily dosing; Accumulates in third spaced fluids

CrCl 61 to 80 mL/min: decrease dose 25%;CrCl 51 to 60 mL/min: decrease dose 30%;CrCl 10 to 50 mL/min: decrease dose 50% to 70%;CrCl <10 mL/min: avoid use

Therapeutic monitoring to ensure clearance and help determine leucovorin doses; Leucovorin rescue administered for doses >1000 mg/m2 until levels fall below 5 x 10-8 M; Urinary alkalinization required for high doses; Acetazolamide may be used with high dose therapy to keep urine pH >7 and avoid nephrotoxicity; Avoid NSAIDs and penicillins (increased risk of toxicity); May be administered intrathecally; Check for pleural effusions prior to administration

Pemetrexed (Alimta) Prevents DNA synthesis but uses more routes than MTX so resistance is less of a problem

None Severe neutropenia may result in sepsis; Anemia; Thrombocytopenia; Interstitial pneumonitis; Erythematous rash

CrCl >80 mL/min: 600 mg/m2;CrCl 40-79 mL/min: 500 mg/m2; Grade 4 transaminase elevation (>20 times ULN): reduce dose by 75%

Use with B12 and folate to lower cystathionine and homocysteine levels and lower risk of death due to neutropenic sepsis; Dexamethasone 4 mg BID the day before, day of, and day after administration helps the rash; Avoid NSAIDs

Biologic and Immune TherapiesRetinoids – Tretinoin (ATRA, Vesanoid), Alitretinoin (Panretin), Bexarotene (Targretin)

Works through retinoid X and retinoic acid receptors to affect the growth and differentiation of cells

PML/RAR (alpha) fusion gene absence predicts poor response

Retinoic acid syndrome - fever, respiratory distress, and hypotension; Skin dryness – cracking of lips; Edema; Headache; Fever; Malaise; Hyperlipidemia; Nausea and vomiting; Pulmonary toxicity

Effects of hepatic or renal dysfunction isn’t known, but may need to hold or discontinue if liver function tests >3xULN

Treat differentiation syndrome with dexamethasone 10 mg every 12 hours



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 may require meperidine; Skin redness 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 that inhibits 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, and acetaminophen

Inhibitors of EGFR ReceptorsCetuximab (Erbitux) Recombinant chimeric

MoAb that binds to endothelial growth factor receptor (EGFR) causing inhibition of cell growth and vascular endothelial growth factor (VEGF) production and increased programmed cellular death (apoptosis)

EGFR mutation may predict benefit; KRAS mutation predicts lack of benefit; Consider BRAF 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 back within the first 2 weeks of therapy; Fatigue; GI effects – nausea, vomiting, diarrhea, constipation, abdominal pain; Hypomagnesemia; Hypersensitivity reactions; Fever

Use diphenhydramine prior to administration

Panitumumab (Vectibix)

Recombinant human IgG2 MoAb that binds to the epidermal growth factor receptor inhibiting cell survival, growth, and proliferation

EGFR mutation may predict benefit; Not recommended 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



Comments

Trastuzumab (Herceptin)

Recombinant humanized MoAb the selectively binds to HER2 that inhibits cell-cycle progression, decreases cell proliferation, and causes apoptosis

Documented HER2/neu over-expression required for use

Cardiomyopathy; Infusion reactions – mild to moderate fever and chills during first cycle; Hypersensitivity reactions; Myelosuppression infrequent when given alone but synergistic when given with traditional agents; Headache; Rash; Insomnia

Cardiac function should be evaluated prior to use; Synergistic with many traditional chemotherapeutic agents; Avoid with anthracyclines due to risk of additive cardiotoxicity; Existing cardiac disease or previous anthracycline therapy: use with extreme caution;Ejection fraction <50% or >10% decrease: consider discontinuing therapy

Miscellaneous AgentsThalidomide (Thalomid)

Most likely immunomodulation resulting in inhibition of angiogenesis

None Somnolence; Constipation; Dizziness; Orthostatic hypotension; Rash; Peripheral neuropathy; Thrombosis

Pregnancy category X; All pharmacies and prescribers must be enrolled in the System for Thalidomide Education and Prescribing Safety (STEPS) program to dispense; Give at least 1 hour after the evening meal

Lenalidomide (Revlimid)

Analog of thalidomide Use with myelodysplastic syndrome with deletion of chromosome 5q(del(5q))

Neutropenia; Thrombocytopenia; Thrombosis

Pregnancy category X; Only available under restricted distribution program RevAssist

Bleomycin (Blenoxane)

Damages DNA strands None Pulmonary toxicity; Frequently causes alopecia; Hyperpigmentation; Raynaud’s syndrome; Anemia; Hypersensitivity reactions; Nausea and vomiting

CrCl 40-50 mL/min: decrease by 30%; CrCl 30-40 mL/min: decrease by 40%; CrCl 20-30 mL/min: decrease by 45%; CrCl 10-20 mL/min: decrease by 55%; CrCl 5-10 mL/min: decrease by 60%

Some use test dose administered prior to the first treatment; Premedicate with acetaminophen to avoid fever; Avoid total dose >450 mg or 200 mg/m2 due to increased risk of pulmonary toxicity; Monitor pulmonary function tests

Hydroxyurea (Hydrea)

Inhibits ribonucleotide reductase

None Myelosuppression; Nausea and vomiting; Diarrhea; Constipation; Palmar-plantar dysesthesias or hand-foot syndrome (redness, tenderness, blistering of palms and soles of the feet); Mucositis

CrCl 10-50 mL/min: decrease dose by 50%; CrCl <10 mL/min: decrease dose by 80%



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; Hypersensitivity reactions

Test dose prior to the first dose or when restarting therapy after 7 days or more; Inhibits synthesis of fibrinogen and other coagulation factors and can 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, pleural or pericardial effusion

Use with caution in renal dysfunction, but effects in renal or hepatic dysfunction are unknown

ECG twice a week during dosing; Avoid other QT prolonging drugs; Monitor and replace potassium and magnesium as needed

Mitomycin C (Mutamycin)

Cross-link DNA None Delayed myelosuppression; Pulmonary toxicity; Hemolytic uremic syndrome; Cardiac toxicity; Pulmonary toxicity

CrCl <10 mL/min: decrease dose by 25%

Vesicant; Extravasation risk

Estramustine (Emcyt)

Inhibits microtubule assembly and weak estrogenic activity

None Edema; Nausea and vomiting; Diarrhea; Thromboembolism; Gynecomastia

Take at least 1 hour before or 2 hours after eating

Miscellaneous Targeting AgentsBortezomib (Velcade)

Inhibits proteasomes (enzyme complex that degrades proteins responsible for cancer growth)

None Usually mild to moderate; Asthenia (fatigue, malaise, weakness); Nausea and diarrhea; Decreased appetite; Constipation; Thrombocytopenia; Anemia; Neutropenia; Peripheral neuropathy; Fever

Bilirubin >1.5x ULN: decrease dose to 0.7 mg/m2

Temsirolimus (Torisel)

Binds to FKBP-12 and inhibits the activity of mammalian target of rapamycin (mTOR) resulting in inhibition of protein synthesis and angiogenesis

None Rash; Fatigue; Mucositis; Nausea; Edema; Loss of appetite; Increases in creatinine and liver function tests; Thrombocytopenia; Neutropenia; Hyperglycemia; Hyperlipidemia; Rash; Shingles

Monitor blood glucose and lipids; Affected by CYP3A4 inhibitors and inducers



Comments

Monoclonal AntibodiesRituximab (Rituxan) Chimeric MoAb directed

against the CD20 antigen on normal and malignant B-cells that causes B-cell lysis

Malignancies with CD20-antigen expression

Hypersensitivity reactions (fever, chills, nausea, asthenia, headache); Tumor lysis; Neutropenia, thrombocytopenia, and anemia are relatively rare; Progressive multifocal encephalopathy

Use diphehydramine and acetaminophen prior to administration; Severe infusion reaction are most likely during the first infusion

Ibritumomab (Zevalin)

Murine anti-CD20 MoAb to which indium-111 (imaging and dosimetry) or yttrium-90 (radiotherapy) are attached causing radiation induced cell death


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 for dosimetry (calculating the necessary radiation dose) and imaging, then a second dose of rituximab followed by Y-90 ibritumomab to deliver radiation directly to cells expressing the CD20 antigen

Tositumomab (Bexxar)

Murine anti-CD20 MoAb that can be linked to I-131 to cause radiation induced cell death


Similar to ibritumomab Renal dysfunction may delay elimination of I-131

Use diphenhydramine and acetaminophen prior to administration; 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 involves naked tositumomab first to lower B-cell count followed by I-131 labeled tositumomab at a lower dose for imaging and dosimetry, then a larger dose if I-131 labeled tositumomab is given to deliver radiation directly to cells expressing the CD20 antigen



Comments

Alemtuzumab (Campath)

Recombinant humanized MoAb against CD52 on leukemic lymphocytes and causing cell death


Severe infusion reactions – fever, severe rigors, mild to moderate nausea and vomiting, rash; Severe prolonged neutropenia and thrombocytopenia; Severe decreases in CD4 and CD8 counts

Use diphenhydramine and acetaminophen prior to administration; Prophylax for P. jiroveci pneumonia with TMP-SMX DS BID three times a week and herpes virus with acyclovir for up to 6 months after therapy or until CD4 counts above 200 cells/mm3

Platinum AnalogsCisplatin (Platinol) Cross-link DNA None Myelosuppressive;

Nephrotoxicity; Severe nausea and vomiting acute and delayed; Hypersensitivity reactions; Encephalopathy (confusion, lethargy, psychosis); Glove and stocking neuropathy; Cranial nerve toxicity (ototoxicity, etc); Hypersensitivity reactions

Repeat courses should not be administered until SCr <1.5 mg/dL and BUN <25 mg/dLCrCl 10-50 mL/min: decrease dose 25%;CrCl <10 mL/min: decrease dose by 50%

Vigorous hydration and sometimes mannitol used to avoid renal failure; Magnesium supplementation may also help prevent electrolyte wasting; Amifostine (Ethyol) may also be used; Mild hypersensitivity reactions may respond to pretreatment with steroids and antihistamines

Carboplatin (Paraplatin-AQ)

Cross-link DNA None Myelosuppression; Less likely than cisplatin to cause kidney damage, peripheral neuropathy, ototoxicity, or nausea and vomiting; Commonly causes anemia/ thrombocytopenia; Hypersensitivity reactions

AUC based dose using Calvert equation: carboplatin dose (mg) = target AUC in mg x min/mL x [CrCl in mL/min + 25] ; Target AUC usually 5 to 7 mg/mL per min for q 3 week administration and AUC 2 for weekly administration; Calculating CrCl: Cockcroft-Gault equation usually used for non-gynecologic malignancies and Jelliffe used for gynecologic malignancies

Mild hypersensitivity reactions may respond to pretreatment with steroids and antihistamines; Likelihood of hypersensitivity increases with repeated dosing

Oxaliplatin (Eloxatin)

Cross-link DNA None Moderate nausea and vomiting; Anemia; Causes glove and stocking and cold-induced neuropathy; Hypersensitivity reactions

CrCl <20 mL/min: use not well studied, consider avoiding

Mild hypersensitivity reactions may respond to pretreatment with steroids and antihistamines



Comments

Purine Antimetabolites6-mercaptopurine (6-MP, Purinethol)

Inhibit purine ring synthesis and nucleotide interconversions

Thiopurine methyltransferase deficiency or lower activity increases the risk of myelotoxicity

Myelosuppression; Nausea; Hepatotoxicity

Decrease dose for hepatic or renal dysfunction

Allopurinol decreases 6-MP metabolism 75% and results in serious toxicity if the 6-MP dose isn’t adjusted; Oral agent must be taken on empty stomach 1 hour before or 2 hours after meals

6-thioguanine (Tabloid)




Decrease dose for hepatic or renal dysfunction

Azathioprine (Imuran)




CrCl 10-50 mL/min: decrease dose by 25%; CrCl <10 mL/min: decrease dose by 50%

Metabolized to 6-MP; Allopurinol significantly decreases metabolism and results in serious toxicity

Fludarabine (Fludara IV)

Interferes with DNA polymerase and inhibits RNA transcription

None Myelosuppression is often dose limiting; Immunosuppressant effects (decreases CD4 counts) can result in opportunistic infections; Severe neurotoxicity (altered mental status, temporary blindness, seizures, paralysis) with doses >90 mg/m2

for 5 to 7 days; Pulmonary toxicity

CrCl 30-70 mL/min: decrease dose by 50%; CrCl <30 mL/min: avoid use (oral: give 50% of dose)

Antibiotic prophylaxis against PCP and antivirals may be used until CD4 count normalizes

Cladribine (Leustatin)

Inhibition of DNA synthesis – effects both rapidly dividing and resting cancer cells

None Immunosuppressant effects (decreases CD4 counts) can result in opportunistic infections

CrCl 10-50 mL/min: decrease dose 25%;CrCl <10 mL/min: decrease dose by 50%

Prophylactic antibiotics and antivirals may be used until CD4 count normalizes

Pentostatin (Nipent) Inhibits adenosine deaminase

None Immunosuppressant effects (decreases CD4 counts) can result in opportunistic infections

CrCl <60 mL/min: administer 70% of dose;CrCl <45 mL/min: administer 60% of dose; CrCl <30 mL/min: consider withholding

Prophylactic antibiotics and antivirals may be used until CD4 count normalizes



Comments

Pyrimidine AntimetabolitesFluorouracil (5-FU) Inhibits thymidylate

synthaseDPD deficiency (increases risk of severe toxicity)

Stomatitis; Diarrhea; Myelosuppression; Cardiac abnormalities – usually angina (ST elevation – especially with cardiovascular disease); Esophageal and gastric ulceration; Cerebellar toxicities (ataxia, incoordination, nystagmus); Frequently causes alopecia; Neurotoxicities include headaches, visual disturbances, and cerebellar ataxia; Palmar-plantar dysesthesias or hand-foot syndrome (redness, tenderness, blistering of palms and soles of the feet); Hyperpigmentation

Avoid use if bilirubin >5 mg/dL (may be used in patients with elevated bilirubin when elevation is due to liver metastases from colorectal cancer)

Given with 25-500 mg leucovorin orally daily to increase 5-FU’s efficacy in GI malignancies; Oral ice chips for 30 minutes during administration may lower the risk of mucositis

Capecitabine (Xeloda)

Prodrug of 5-FU DPD deficiency (increases risk of severe toxicity)

Same as for 5-FU plus edema and dermatitis; Increased risk of hand-foot syndrome

CrCl 30-50 mL/min: decrease dose by 25%; CrCl <30 mL/min: contraindicated

Take within 30 minutes of a meal; Avoid in patients on warfarin (significantly increases INR); 2C9 inhibitor so may increase phenytoin levels



Comments

Cytarabine (Ara-C, Cytosar)

Cytarabine liposomal (DepoCyt)

Inhibits DNA polymerase None Hepatotoxicity; Myelosuppression; Stomatitis; Diarrhea; Noncardiogenic pulmonary edema; Cerebellar syndrome (nystagmus, dysarthria, ataxia) especially with advanced age and renal dysfunction; Encephalopathy (confusions, seizures, coma); Intrathecal use can cause chemical meningitis; Eye irritation; Palmar-plantar dysesthesias or hand-foot syndrome (redness, tenderness, blistering of palms and soles of the feet)

SCr = 1.5-1.9 mg/dL or increased 0.5-1.2 mg/dL: no more than 1 g/m2; If Cr >1.9 mg/dL or increased >1.2 mg/dL: decrease dose to 0.1 g/m2 per day; Bilirubin >2 mg/dL: administer 50% of the dose

Dosing range for cytarabine is highly variable; Be sure to know the dose and method of administration; Avoid high dose therapy when age >60y; May be administered intrathecally

Gemcitabine (Gemzar)

Inhibits DNA polymerase and ribonucleotide reductase

None Myelosuppression; Nausea; Flu-like syndrome (during the first 24 hours); Rash after 48 to 72 hours; Pulmonary toxicity; Hepatoxicity; Hemolytic uremic syndrome

Bilirubin >1.6 mg/dL: decrease dose by 20%;Bilirubin >7.5 mg/dL: avoid use

Use acetaminophen for fevers; Specific dose adjustments are based on hematologic toxicities (absolute neutrophil count and platelets)

Azacitidine (5AZC, Vidaza)

Not completely understood; Inhibits DNA methyltransferaseinsertion into DNA; Promotes hypomethylation of DNA normalizing 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 methyltransferaseinsertion into DNA; Promotes hypomethylation of DNA normalizing 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



Comments

Paclitaxel (Taxol)

Paclitaxel albumin-bound (Abraxane)

Inhibit function of microtubules; 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 <2xULN and bilirubin <1.5 mg/dL: 135 mg/m2;Transaminases 2 to <10xULN and bilirubin <1.5 mg/dL: 100 mg/m2; Transaminases <10xULN and bilirubin 1.6 to 7.5 mg/dL: 50 mg/m2;Transaminases >10xULN or bilirubin >7.5 mg/dL: avoid3-hour infusion:Transaminases <10xULN and bilirubin <1.25xULN: 175 mg/m2;Transaminases <10xULN and bilirubin 1.26 to 2xULN: 135 mg/m2;Transaminases <10xULN and bilirubin 2.01 to 5xULN: 90 mg/m2;Transaminases >10xULN or bilirubin >5xULN: avoid

Premedicate with steroids, antihistamines, and H2 antagonists unless using albumin-bound product; Affected by CYP 2C9, 2C8, and 3A4 inhibitors and inducers; When given with doxorubicin separate doses by 24 hours to avoid enhanced doxorubicin exposure; Administer before cisplatin to avoid reduced clearance of paclitaxel; Lower dose of gemcitabine when administered concurrently; Lower warfarin dose and monitor INR when used concurrently

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 hypersensitivity reactions; Administer before cisplatin to avoid reduced clearance of docetaxel; Lower the dose of gemcitabine when administered concurrently; Lower warfarin dose and monitor INR when used concurrently

Topoisomerase Inhibitors



Comments

Etoposide (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-asthmatic episode after infusion; Mucositis

CrCl 10-50 mL/min: decrease dose by 25%; CrCl <10 mL/min: decrease dose by 50%; Bilirubin 1.5-3 mg/dL or AST 60 to 180 units: decrease dose by 50%; Bilirubin 3 to 5 mg/dL or AST >180 units: decrease dose by 75%;Bilirubin >5 mg/mL: Don’t administer

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

Irinotecan (Camptosar)

Damage DNA and prevent repair

Reduce starting dose by at least one level in patients homozygous for the UGT1A1*28 allele

Early diarrhea (with cramping and flushing) and late onset severe diarrhea; Myelosuppression; Frequently causes alopecia; Nausea and vomiting; Pulmonary toxicity

Bilirubin >2 mg/dL or transaminases >3xULN (without liver metastases) or transaminases >5xULN (with liver metastases): contraindicated

Often results in cholinergic symptoms (rhinitis, increased salivation, miosis, flushing, abdominal cramping) during infusion or within 24 hours after treatment; Atropine 0.25 to 1 mg IV or subcutaneously as a pre-medication or PRN med can help; Use loperamide 2 mg every 2 to 4 hours for late onset diarrhea; Medical emergency if not resolved in < 24h; Use caution in CYP450 3A4/2B6 inhibitors and inducers (may need a much higher dose with inducers)

Topotecan (Hycamtin)

Damage DNA and prevent repair

None Myelosuppression; Mucositis; Nausea and vomiting; Mild alopecia; Fatigue; Rash; Mild diarrhea

CrCl 20-30 mL/min: decrease dose by 75;CrCl <20 mL/min: not established

Tyrosine Kinase Inhibitors



Comments

Gefitinib (Iressa) Orally active selective EGFR-tyrosine kinase inhibitors that block cell proliferation, survival, and metastases

EGFR mutation may predict benefit; KRAS mutation predicts lack of benefit

Acne-like or erythematous rashes most commonly on the face that may respond to steroid creams, acne oral or topical antibiotics, or oral antihistamines; Diarrhea

Effect of hepatic impairment unknown

No survival benefit in inoperable non-small cell lung cancer (NSCLC) so only for patients who have failed other therapies and previously benefited from it

Erlotinib (Tarceva) Orally active selective EGFR-tyrosine kinase inhibitors that block cell proliferation, survival, and metastases

EGFR expression may predict benefit with therapy; KRAS mutation predicts lack of benefit

Rash (similar to cetuximab); Interstitial lung disease; Diarrhea; Fatigue; Anorexia; Nausea and vomiting; Stomatitis; Hepatotoxicity; Conjunctivitis

Stop therapy if bilirubin increases to >3xULN or transaminases >5xULN; If baseline bilirubin >3xULN: Use caution, consider using 75 mg daily

Take on an empty stomach – 1 hour before or 2 hours after a meal; Monitor warfarin for increasing INR; Affected by inhibitors or inducers of CYP3A4

Lapatinib (Tykerb) 4-anilinoquinazoline kinase inhibitor that inhibits both EGFR and HER2

HER2/neu over-expression required for use

Myelosuppression; Diarrhea; Hepatotoxicity; Rash; QT interval prolongation; Hand-and-foot syndrome

Severe hepatic impairment: consider using 750 mg daily

Additive activity with some traditional chemotherapeutic agents; Affected by inhibitors or inducers of CYP3A4; Give on an empty stomach

Imatinib (Gleevec) Selective inhibitor of BCR-Abl tyrosine kinase resulting in prevention of cell proliferation, apoptosis, and arrest of growth in cells expressing BCR-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 for c-KIT (CD117)-positive tumors; 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-Johnson’s syndrome 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 by 3A4 inhibitors and inducers

Dasatinib (Sprycel) Same as imatinib but retains activity in imatinib resistant cases; Inhibits Src 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, or shortness 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, and CYP2D6



Comments

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 over 50 mg/day

Affected by 3A4 inhibitors and inducers

Sorafenib (Nexavar) Similar to above, plus inhibits serine/threonine kinase Raf which is involved in cell proliferation

None Diarrhea; Rash; Fatigue; Hypertension; Palmar-plantar dysesthesias or hand-foot syndrome (redness, tenderness, blistering of palms and soles of the feet)

Vinca AlkaloidsVincristine (Vincasar PFS, Oncovin)

Inhibit function of microtubules

None Mild myelosuppression; Neurotoxicity (paresthesias, depression of reflexes, stumbling, falling); Loss of reflexes 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 by 75%;Bilirubin >5 mg/dL or AST >180 units: avoid use

Vesicant; Fatal if given intrathecally; Stimulant laxatives (senna, bisacodyl) +/- stool softener prophylactically to prevent constipation; Some cap the total dose at 2 mg to avoid neuropathic side effects; Affected by CYP 3A4 inhibitors or inducers (for example, itraconazole can cause severe neurotoxicity when administered concurrently)



Comments

Vinblastine (Velban)


None Dose limiting myelosuppression; Neurotoxicity less than vincristine (paresthesias, depression of reflexes, stumbling, falling); Cranial nerve toxicity (lid lag, facial palsy, trigeminal neuralgia); Constipation; Pulmonary toxicity in combo with mitomycin; Rash; Stomatitis

Bilirubin 1.5-3.0 mg/dL or AST 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 given intrathecally; Affected by CYP 3A4 inhibitors or inducers

Vinorelbine (Navelbine)


None Dose limiting myelosuppression; Dyspnea/cough; Neurotoxicity (paresthesias, depression of reflexes, stumbling, falling); Cranial nerve toxicity (lid lag, facial palsy, trigeminal neuralgia)

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 leukemiaCrCl = creatinine clearancePCP = Pneumocystis pneumoniaSCr = serum creatinineSIADH = syndrome of inappropriate antidiuretic hormoneULN = upper limit of normal

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