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Common Chemotherapy Agents

Agent Mechanism Genetic Issues Side Effects Alkylating Agents 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 Myelosuppression; Alopecia; Pulmonary toxicity (after at least 6 mo. of treatment with a total cumulative dose >2 g) Renal/Hepatic Dosage Adjustment CrCl <10 mL/min: decrease dose by 25%; Bilirubin 3.15 mg/dL or transaminases >3xULN: decrease dose 25% Comments 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

Cyclophosphamide (Cytoxan)

Cross-link DNA

None

Chlorambucil (Leukeran)

Cross-link DNA

None

Busulfan (Myleran, Busulfex)

Cross-link DNA

Philadelphia (Ph1) chromosome absence predicts poor leukemia response

Ifosfamide (Ifex)

Cross-link DNA

None

Carmustine (BiCNU, Gliadel)

Cross-link DNA

None

Lomustine (CeeNU)

Cross-link DNA

None

Prolonged myelosuppression; Hyperpigmentation; Pulmonary toxicity; Severe nausea and vomiting, seizures, and sinusoidal obstruction syndrome with high doses Myelosuppression; Hemorrhagic cystitis; Frequently causes alopecia; Encephalopathy (confusion, lethargy, psychosis); Cranial nerve toxicity (lid lag, facial palsy, trigeminal neuralgia) 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) 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%; Dosage adjustment may be necessary with hepatic dysfunction Dosage adjustment may be needed with hepatic dysfunction

Anticonvulsant prophylaxis for patients receiving high doses

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

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

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

Common Chemotherapy Agents


Agent Dacarbazine (DTIC) Mechanism Alkylation of DNA leading to inhibition of DNA, RNA, and protein synthesis Genetic Issues None Side Effects Myelosuppression; Severe nausea and vomiting; Flu-like syndrome starting a week after treatment and lasting 1 to 3 weeks Myelosuppression; Nausea and vomiting; Headache; Fatigue; Constipation; Immunosuppressive with continuous dosing Myelosuppression; Nausea and vomiting; Flu-like syndrome; Encephalopathy (confusion, lethargy, psychosis); Pulmonary toxicity Myelosuppression; Nausea and vomiting; Venous irritation Less prominent myelosuppression; Nausea; Encephalopathy (confusion, lethargy, psychosis); Mood swings; Neuropathy Myelosuppression; Nausea and vomiting; Pulmonary toxicity not dose related; Anorexia; Diarrhea; Neuropathy; Agitation; Confusion Myelosuppression; Nausea and vomiting Renal/Hepatic Dosage Adjustment 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% Dosage adjustments may be needed with moderate to severe renal or hepatic dysfunction SCr >2 mg/dL or bilirubin >3 mg/dL: decrease the dose; SCr >5 mg/dL or transaminases >3xULN: consider avoiding Reduced dose may be necessary for patients with renal impairment Comments Doesnt cross the blood-brain barrier

Temozolomide (Temodar)

Alkylation of DNA leading to inhibition of DNA, RNA, and protein synthesis Alkylation of DNA leading to inhibition of DNA, RNA, and protein synthesis Cross-link DNA

Increased sensitivity with MGMT promoter methylation

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

Procarbazine (Matulane)

None

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

Thiotepa

None

Altretamine (Hexalen)

Cross-links DNA

None

Barbiturates increases metabolism; Cimetidine inhibits metabolism

Melphalan (Alkeran)

Cross-link DNA

None

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

Mechlorethamine (Mustargen)

Cross-link DNA

None

Common Chemotherapy Agents


Agent Mechanism Genetic Issues Side Effects Angiogenesis Inhibitors 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 Renal/Hepatic Dosage Adjustment Comments

Bevacizumab (Avastin)

Recombinant humanized MoAb directed against VEGF that prevents neoangiogenesis

None

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 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

Daunorubicin (Cerubidine) Daunorubicin liposomal (DaunoXome)

Intercalate with DNA and inhibit RNA synthesis; Topoisomerase II inhibitor

None

Anthracyclines Myelosuppression; Cardiotoxicity; Frequently causes alopecia; Mucositis; Mild to moderate nausea and vomiting; Red urine

Common Chemotherapy Agents


Agent Doxorubicin (Adriamycin) Doxorubicin liposomal (Doxil) Mechanism Intercalate with DNA and inhibit RNA synthesis; Topoisomerase II inhibitor Genetic Issues HER2 breast cancers are often sensitive to anthracyclines Side Effects 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 Renal/Hepatic Dosage Adjustment Bilirubin >3 mg/dL: decrease dose by 75% Bilirubin >1.5 mg/dL: decrease dose by 50% Comments 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 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 Vesicant; Extravasation can cause significant injury; Avoid cumulative dose >150 mg/m2 to avoid significant risk of cardiomyopathy

Epirubicin (Ellence)

Intercalate with DNA and inhibit RNA synthesis; Topoisomerase II inhibitor

HER2 breast cancers are often sensitive to anthracyclines

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

Idarubicin (Idamycin)

Intercalate with DNA and inhibit RNA synthesis; Topoisomerase II inhibitor

HER2 breast cancers are often sensitive to anthracyclines

Myelosuppression; Cardiotoxicity; Mucositis; Red urine; Mild to moderate 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 Bilirubin >5 mg/dL: avoid use; Consider dose reductions for bilirubins lower than this (no published guidelines)

Common Chemotherapy Agents


Agent Mitoxantrone (Novantrone) Mechanism Not technically an anthracycline but often listed with them; Intercalate with DNA and inhibit RNA synthesis; Topoisomerase II inhibitor Prevents DNA synthesis Genetic Issues HER2 breast cancers are often sensitive to anthracyclines Side Effects Myelosuppression; Cardiotoxicity (less than doxorubicin); Blue urine, sclerae, and nails; Nausea and vomiting Renal/Hepatic Dosage Adjustment Consider dose reduction with hepatic dysfunction (no published guidelines) Comments Less extravasation injury; Avoid a total cumulative dose of >160 mg/m2 or >100 mg/m2 with previous doxorubicin due to risk of cardiomyopathy

Methotrexate (MTX)

None

Antifolates 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

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%

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 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 Treat differentiation syndrome with dexamethasone 10 mg every 12 hours

Retinoids Tretinoin (ATRA, Vesanoid), Alitretinoin (Panretin), Bexarotene (Targretin)

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

Biologic and Immune Therapies PML/RAR (alpha) Retinoic acid syndrome - fever, fusion gene absence respiratory distress, and predicts poor response hypotension; Skin dryness cracking of lips; Edema; Headache; Fever; Malaise; Hyperlipidemia; Nausea and vomiting; Pulmonary toxicity

Effects of hepatic or renal dysfunction isnt known, but may need to hold or discontinue if liver function tests >3xULN

Common Chemotherapy Agents


Agent Aldesleukin (IL-2, Proleukin) Mechanism Stimulates the development of cytoxic cells that recognize and destroy tumor cells Genetic Issues None Side Effects 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 Renal/Hepatic Dosage Adjustment Comments 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 Slow the rate or interrupt the infusion for hypersensitivity reactions and treat with a steroid, antihistamine, and acetaminophen

Denileukin (Ontak)

Recombinant fusion protein combining active portions of IL-2 and diphtheria toxin that inhibits protein synthesis and causes cell death

None

Cetuximab (Erbitux)

Panitumumab (Vectibix)

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

Acute hypersensitivity reactions hypotension, vasodilation, rash, chest tightness; Flu-like symptoms; Diarrhea; Vascularleak syndrome (delayed onset and usually self-limited); Nausea and vomiting; Asthenia; Hepatotoxicity Inhibitors of EGFR Receptors EGFR mutation may Severe infusion reactions predict benefit; KRAS airway obstruction and mutation predicts lack hypotension; Acne-like rash on of benefit; Consider face upper chest, and back BRAF testing if within the first 2 weeks of BRAF mutation is therapy; Fatigue; GI effects present may predict nausea, vomiting, diarrhea, lack of response constipation, abdominal pain; Hypomagnesemia; Hypersensitivity reactions; Fever EGFR mutation may Dermatologic toxicities common predict benefit; Not (acne-like lesions, itching, recommended to use redness, rash, skin exfoliation, with KRAS mutation; etc); Diarrhea Consider BRAF testing if BRAF mutation is present may predict lack of response

Use diphenhydramine prior to administration

Common Chemotherapy Agents


Agent Trastuzumab (Herceptin) Mechanism Recombinant humanized MoAb the selectively binds to HER2 that inhibits cell-cycle progression, decreases cell proliferation, and causes apoptosis Genetic Issues Documented HER2/neu over-expression required for use Side Effects 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 Renal/Hepatic Dosage Adjustment Comments 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 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 Pregnancy category X; Only available under restricted distribution program RevAssist

Thalidomide (Thalomid)

Most likely immunomodulation resulting in inhibition of angiogenesis

None

Miscellaneous Agents Somnolence; Constipation; Dizziness; Orthostatic hypotension; Rash; Peripheral neuropathy; Thrombosis

Lenalidomide (Revlimid)

Analog of thalidomide

Bleomycin (Blenoxane)

Damages DNA strands

Use with myelodysplastic syndrome with deletion of chromosome 5q(del(5q)) None

Neutropenia; Thrombocytopenia; Thrombosis

Pulmonary toxicity; Frequently causes alopecia; Hyperpigmentation; Raynauds syndrome; Anemia; Hypersensitivity reactions; Nausea and vomiting

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 40-50 mL/min: decrease by 30%; CrCl 3040 mL/min: decrease by 40%; CrCl 20-30 mL/min: decrease by 45%; CrCl 1020 mL/min: decrease by 55%; CrCl 5-10 mL/min: decrease by 60% CrCl 10-50 mL/min: decrease dose by 50%; CrCl <10 mL/min: decrease dose by 80%

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

Common Chemotherapy Agents


Agent L-Asparaginase (Elspar) Mechanism Deaminates asparagines and inhibits protein synthesis Genetic Issues None Side Effects Hepatotoxicity; Encephalopathy (lethargy and confusion); Occasional cerebral dysfunction (stupor, coma, disorientation, hallucinations); Pancreatitis; Hyperglycemia; Hypersensitivity reactions Renal/Hepatic Dosage Adjustment Comments 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 ECG twice a week during dosing; Avoid other QT prolonging drugs; Monitor and replace potassium and magnesium as needed

Arsenic trioxide (Trisenox)

Metabolized to arsenic that damages genes in leukemic cells

None

Mitomycin C (Mutamycin)

Cross-link DNA

None

Estramustine (Emcyt)

Inhibits microtubule assembly and weak estrogenic activity Inhibits proteasomes (enzyme complex that degrades proteins responsible for cancer growth)

None

Bortezomib (Velcade)

None

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

Prolongation of QT interval; Peripheral neuropathy; Musculoskeletal pain; Dry skin; Hyperglycemia; APL differentiation syndrome: pulmonary dysfunction, pleural or pericardial effusion Delayed myelosuppression; Pulmonary toxicity; Hemolytic uremic syndrome; Cardiac toxicity; Pulmonary toxicity Edema; Nausea and vomiting; Diarrhea; Thromboembolism; Gynecomastia Miscellaneous Targeting Agents Usually mild to moderate; Asthenia (fatigue, malaise, weakness); Nausea and diarrhea; Decreased appetite; Constipation; Thrombocytopenia; Anemia; Neutropenia; Peripheral neuropathy; Fever Rash; Fatigue; Mucositis; Nausea; Edema; Loss of appetite; Increases in creatinine and liver function tests; Thrombocytopenia; Neutropenia; Hyperglycemia; Hyperlipidemia; Rash; Shingles

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

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

Vesicant; Extravasation risk

Take at least 1 hour before or 2 hours after eating

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

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

Common Chemotherapy Agents


Agent Mechanism Genetic Issues Side Effects Monoclonal Antibodies Hypersensitivity reactions (fever, chills, nausea, asthenia, headache); Tumor lysis; Neutropenia, thrombocytopenia, and anemia are relatively rare; Progressive multifocal encephalopathy Infusion reactions including lifethreatening anaphylaxis with greatest risk during the first infusion of rituximab; Prolonged thrombocytopenia and neutropenia are common Renal/Hepatic Dosage Adjustment Comments

Rituximab (Rituxan)

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

Malignancies with CD20-antigen expression

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

Malignancies with CD20-antigen expression

Tositumomab (Bexxar)

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

Malignancies with CD20-antigen expression

Similar to ibritumomab

Renal dysfunction may delay elimination of I-131

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 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 I131 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

Common Chemotherapy Agents


Agent Alemtuzumab (Campath) Mechanism Recombinant humanized MoAb against CD52 on leukemic lymphocytes and causing cell death Genetic Issues Malignancies with CD52-antigen expression Side Effects 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 Platinum Analogs 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 Myelosuppression; Less likely than cisplatin to cause kidney damage, peripheral neuropathy, ototoxicity, or nausea and vomiting; Commonly causes anemia/ thrombocytopenia; Hypersensitivity reactions Renal/Hepatic Dosage Adjustment Comments Use diphenhydramine and acetaminophen prior to administration; Prophylax for P. jiroveci pneumonia with TMPSMX 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 Repeat courses should not be administered until SCr <1.5 mg/dL and BUN <25 mg/dL CrCl 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 Mild hypersensitivity reactions may respond to pretreatment with steroids and antihistamines; Likelihood of hypersensitivity increases with repeated dosing

Cisplatin (Platinol)

Cross-link DNA

None

Carboplatin (Paraplatin-AQ)

Cross-link DNA

None

Oxaliplatin (Eloxatin)

Cross-link DNA

None

Moderate nausea and vomiting; Anemia; Causes glove and stocking and cold-induced neuropathy; 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 CrCl <20 mL/min: use not well studied, consider avoiding

Mild hypersensitivity reactions may respond to pretreatment with steroids and antihistamines

Common Chemotherapy Agents


Agent Mechanism Genetic Issues Side Effects Purine Antimetabolites Myelosuppression; Nausea; Hepatotoxicity Renal/Hepatic Dosage Adjustment Decrease dose for hepatic or renal dysfunction Comments

6-mercaptopurine (6-MP, Purinethol)

Inhibit purine ring synthesis and nucleotide interconversions

Thiopurine methyltransferase deficiency or lower activity increases the risk of myelotoxicity

Allopurinol decreases 6-MP metabolism 75% and results in serious toxicity if the 6-MP dose isnt adjusted; Oral agent must be taken on empty stomach 1 hour before or 2 hours after meals

6-thioguanine (Tabloid)

Inhibit purine ring synthesis and nucleotide interconversions

Azathioprine (Imuran)

Inhibit purine ring synthesis and nucleotide interconversions

Fludarabine (Fludara IV)

Interferes with DNA polymerase and inhibits RNA transcription

Thiopurine methyltransferase deficiency or lower activity increases the risk of myelotoxicity Thiopurine methyltransferase deficiency or lower activity increases the risk of myelotoxicity None

Myelosuppression; Nausea; Hepatotoxicity

Decrease dose for hepatic or renal dysfunction

Myelosuppression; Nausea; Hepatotoxicity

CrCl 10-50 mL/min: decrease dose by 25%; CrCl <10 mL/min: decrease dose by 50% CrCl 30-70 mL/min: decrease dose by 50%; CrCl <30 mL/min: avoid use (oral: give 50% of dose)

Metabolized to 6-MP; Allopurinol significantly decreases metabolism and results in serious toxicity Antibiotic prophylaxis against PCP and antivirals may be used until CD4 count normalizes

Cladribine (Leustatin)

Pentostatin (Nipent)

Inhibition of DNA synthesis effects both rapidly dividing and resting cancer cells Inhibits adenosine deaminase

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 Immunosuppressant effects (decreases CD4 counts) can result in opportunistic infections Immunosuppressant effects (decreases CD4 counts) can result in opportunistic infections

None

CrCl 10-50 mL/min: decrease dose 25%; CrCl <10 mL/min: decrease dose by 50% 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 Prophylactic antibiotics and antivirals may be used until CD4 count normalizes

Common Chemotherapy Agents


Agent Mechanism Genetic Issues Side Effects Renal/Hepatic Dosage Adjustment 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) Comments

Fluorouracil (5-FU)

Inhibits thymidylate synthase

Capecitabine (Xeloda)

Prodrug of 5-FU

Pyrimidine Antimetabolites DPD deficiency Stomatitis; Diarrhea; (increases risk of severe Myelosuppression; Cardiac toxicity) 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; Palmarplantar dysesthesias or hand-foot syndrome (redness, tenderness, blistering of palms and soles of the feet); Hyperpigmentation DPD deficiency Same as for 5-FU plus edema (increases risk of severe and dermatitis; Increased risk of toxicity) hand-foot syndrome

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

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

Cytarabine (Ara-C, Cytosar) Cytarabine liposomal (DepoCyt)

Inhibits DNA polymerase

None

Gemcitabine (Gemzar)

Inhibits DNA polymerase and ribonucleotide reductase

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) Myelosuppression; Nausea; Flulike syndrome (during the first 24 hours); Rash after 48 to 72 hours; Pulmonary toxicity; Hepatoxicity; Hemolytic uremic syndrome

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

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)

Common Chemotherapy Agents


Agent Azacitidine (5AZC, Vidaza) Mechanism Not completely understood; Inhibits DNA methyltransferase insertion into DNA; Promotes hypomethylation of DNA normalizing cells that control cell differentiation Not completely understood; Inhibits DNA methyltransferase insertion into DNA; Promotes hypomethylation of DNA normalizing cells that control cell differentiation Inhibit function of microtubules; Inhibition of angiogenesis Genetic Issues None Side Effects Myelosuppression; Renal tubular acidosis; Renal dysfunction; Injection-site reactions; Nausea and vomiting with high doses Renal/Hepatic Dosage Adjustment Renally excreted, so some experts suggest delaying the next cycle and reducing dose by 50% if increases in BUN/SCr occur Comments

Decitabine (Dacogen)

None

Myelosuppression; Injection-site reactions with non-IV dosing

Hold for SCr >2 mg/dL or ALT/Bilirubin >2xULN

Paclitaxel (Taxol) Paclitaxel albuminbound (Abraxane)

None

Taxanes 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: avoid 3-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

Common Chemotherapy Agents


Agent Docetaxel (Taxotere) Mechanism Inhibit function of microtubules; Inhibition of angiogenesis Genetic Issues None Side Effects Myelosuppression; Stomatitis; Fluid retention; Frequently causes alopecia; Neurotoxicity (numbness); Hypersensitivity reactions Renal/Hepatic Dosage Adjustment Bilirubin > ULN or transaminases >1.5xULN with alkaline phosphatase >2.5xULN: contraindicated Comments Premedicate with dexamethasone 8 mg BID for 35 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

Etoposide (VePesid, VP-16)

Damage DNA and prevent repair; Topoisomerase II inhibitor

None

Topoisomerase Inhibitors Myelosuppression; Neurotoxicity (numbness) Hepatotoxicity with high dose; Alopecia; Nausea and vomiting; Hypotension-fever-asthmatic episode after infusion; Mucositis

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

CrCl 10-50 mL/min: decrease dose by 25%; CrCl <10 mL/min: decrease dose by 50%; Bilirubin 1.53 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: Dont administer Dose adjustment may be necessary for renal or hepatic dysfunction

Common Chemotherapy Agents


Agent Irinotecan (Camptosar) Mechanism Damage DNA and prevent repair Genetic Issues Reduce starting dose by at least one level in patients homozygous for the UGT1A1*28 allele Side Effects Early diarrhea (with cramping and flushing) and late onset severe diarrhea; Myelosuppression; Frequently causes alopecia; Nausea and vomiting; Pulmonary toxicity Renal/Hepatic Dosage Adjustment Bilirubin >2 mg/dL or transaminases >3xULN (without liver metastases) or transaminases >5xULN (with liver metastases): contraindicated Comments 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

Gefitinib (Iressa)

Orally active selective EGFR-tyrosine kinase inhibitors that block cell proliferation, survival, and metastases Orally active selective EGFR-tyrosine kinase inhibitors that block cell proliferation, survival, and metastases 4-anilinoquinazoline kinase inhibitor that inhibits both EGFR and HER2

Erlotinib (Tarceva)

Lapatinib (Tykerb)

Myelosuppression; Mucositis; Nausea and vomiting; Mild alopecia; Fatigue; Rash; Mild diarrhea Tyrosine Kinase Inhibitors EGFR mutation may Acne-like or erythematous predict benefit; KRAS rashes most commonly on the mutation predicts lack face that may respond to steroid of benefit creams, acne oral or topical antibiotics, or oral antihistamines; Diarrhea EGFR expression may Rash (similar to cetuximab); predict benefit with Interstitial lung disease; therapy; KRAS Diarrhea; Fatigue; Anorexia; mutation predicts lack Nausea and vomiting; of benefit Stomatitis; Hepatotoxicity; Conjunctivitis HER2/neu overMyelosuppression; Diarrhea; expression required for Hepatotoxicity; Rash; QT use interval prolongation; Hand-andfoot syndrome

None

CrCl 20-30 mL/min: decrease dose by 75; CrCl <20 mL/min: not established 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 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 Additive activity with some traditional chemotherapeutic agents; Affected by inhibitors or inducers of CYP3A4; Give on an empty stomach

Stop therapy if bilirubin increases to >3xULN or transaminases >5xULN; If baseline bilirubin >3xULN: Use caution, consider using 75 mg daily Severe hepatic impairment: consider using 750 mg daily

Common Chemotherapy Agents


Agent Imatinib (Gleevec) Mechanism 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 Same as imatinib but retains activity in imatinib resistant cases; Inhibits Src kinase Same as imatinib but retains activity in imatinib resistant cases Genetic Issues BCR-ABL testing for Philadelphia chromosome-positive (Ph+) leukemia and cKIT expression for cKIT (CD117)-positive tumors; T315I mutations can decrease response Side Effects Myelosuppression; Mild to moderate edema, but severe fluid retention can occur; Liver function test elevation; Nausea; Muscle cramps; Headache; Rash (rare Stevens-Johnsons syndrome requiring permanently stopping therapy) Renal/Hepatic Dosage Adjustment Effect of hepatic or renal impairment unknown Comments 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)

BCR-ABL testing for Philadelphia chromosome-positive (Ph+) leukemia BCR-ABL testing for Philadelphia chromosome-positive (Ph+) leukemia; UGT1A1*28 predicted increases in bilirubin None

Similar to above

Nilotinib (Tasigna)

Myelosuppression; Rash; Pruritus; Nausea; Fatigue; Headache; Constipation; Diarrhea; Vomiting; QT prolongation 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 Diarrhea; Rash; Fatigue; Hypertension; Palmar-plantar dysesthesias or hand-foot syndrome (redness, tenderness, blistering of palms and soles of the feet)

Indicated for leukemia resistant to imatinib; Monitor for swelling of legs, feet, or shortness of breath; Affected by 3A4 inhibitors and inducers Indicated for leukemia resistant to imatinib; Inhibitor of CYP2C8, CYP2C9, and CYP2D6

Sunitinib (Sutent)

Inhibitor of tyrosine kinase, VEGFR-2, platelet derived growth factor receptor, c-KIT (GI stromal tumors), and FLT3 (leukemia)

Affected by 3A4 inhibitors and inducers

Sorafenib (Nexavar)

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

None

Common Chemotherapy Agents


Agent Mechanism Genetic Issues Side Effects Vinca Alkaloids 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 Renal/Hepatic Dosage Adjustment 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 Comments

Vincristine (Vincasar PFS, Oncovin)

Inhibit function of microtubules

None

Vinblastine (Velban)

Inhibit function of microtubules

None

Vinorelbine (Navelbine)

Inhibit function of microtubules

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 Dose limiting myelosuppression; Dyspnea/cough; Neurotoxicity (paresthesias, depression of reflexes, stumbling, falling); Cranial nerve toxicity (lid lag, facial palsy, trigeminal neuralgia)

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) Vesicant; Fatal if given intrathecally; Affected by CYP 3A4 inhibitors or inducers

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 pneumonia SCr = serum creatinine SIADH = syndrome of inappropriate antidiuretic hormone ULN = upper limit of normal