Download pdf - Chemotherapy Certification Course Syllabus Part 1

Introduction to Antineoplastic Introduction to Antineoplastic PrescribingPrescribing

Robert Bradbury, R.Ph., BCPSRobert Bradbury, R.Ph., BCPSClinical CoordinatorClinical Coordinator

H. Lee Moffitt Cancer CenterH. Lee Moffitt Cancer Center

ObjectivesObjectives

• Meet the following goals concerning antineoplastic prescribing:

– Understand the basis for chemotherapy.

– Be able to identify appropriate dosage ranges.

– Be able to identify major toxicities.

– Learn the skill of prescribing chemotherapy.

• Meet the following goals concerning antineoplastic prescribing:

– Understand the basis for chemotherapy.

– Be able to identify appropriate dosage ranges.

– Be able to identify major toxicities.

– Learn the skill of prescribing chemotherapy.

OverviewOverview

• Cell Cycle Kinetics

• Pharmacologic Classification of Antineoplastic Agents

• Review of Agents

• Review of Combination Therapy

• Cell Cycle Kinetics

• Pharmacologic Classification of Antineoplastic Agents

• Review of Agents

• Review of Combination Therapy

The Cell Cycle The Cell Cycle

G0Resting Phase

SG1

G2

M

Mitosis (Cell Division)

DNA Synthesis

PremitoticPhaseRNA Synthesis

Cell Death

Cell Maturation

Therapy ConceptsTherapy Concepts

• Phase Specific drugs – work only on a specific phase of cell growth– most effective in rapidly growing cells

• Phase Non-Specific drugs – work on more than one phase of cell growth– most effective in rapidly growing cells

• Phase Specific drugs – work only on a specific phase of cell growth– most effective in rapidly growing cells

• Phase Non-Specific drugs – work on more than one phase of cell growth– most effective in rapidly growing cells


• Chemotherapy Terminology

– Induction- drug therapy used as primary treatment (leukemia)

– Consolidation - drug therapy used as follow up after remission from induction (leukemia)

– Adjuvant- drug therapy after surgery or XRT

– Neo-adjuvant - drug therapy before surgery or XRT which is not adequate alone.

– Salvage - drug therapy when primary drug treatment after relapse.

• Chemotherapy Terminology

– Induction- drug therapy used as primary treatment (leukemia)

– Consolidation - drug therapy used as follow up after remission from induction (leukemia)

– Adjuvant- drug therapy after surgery or XRT

– Neo-adjuvant - drug therapy before surgery or XRT which is not adequate alone.

– Salvage - drug therapy when primary drug treatment after relapse.


• Chemotherapy Terminology (cont)

– Regional - drug therapy localized to a specific area (e.g. limb perfusion, intrathecal, intraperitoneal)

– Maintenance - drug therapy used to maintain stable disease or remission.

– High Dose - doses above the standard range used primarily in combo with bone marrow rescue. Assumption that dose-intensity is effective.

– Palliation - drug therapy given to reduce symptoms without an intent to cure disease.

• Chemotherapy Terminology (cont)

– Regional - drug therapy localized to a specific area (e.g. limb perfusion, intrathecal, intraperitoneal)

– Maintenance - drug therapy used to maintain stable disease or remission.

– High Dose - doses above the standard range used primarily in combo with bone marrow rescue. Assumption that dose-intensity is effective.

– Palliation - drug therapy given to reduce symptoms without an intent to cure disease.


• Response Criteria

– Complete Response - Complete disappearance of signs and symptoms for at least 1 month.

– Partial Response - >50% reduction of tumor mass of all measured lesions and no new lesions.

– Stable Disease - No significant change in tumor mass neither increasing or decreasing by 25%.

– Progressive Disease- More than 25% increase in tumor mass

• Response Criteria

– Complete Response - Complete disappearance of signs and symptoms for at least 1 month.

– Partial Response - >50% reduction of tumor mass of all measured lesions and no new lesions.

– Stable Disease - No significant change in tumor mass neither increasing or decreasing by 25%.

– Progressive Disease- More than 25% increase in tumor mass


• Gompertzian Model of Tumor Growth

– Growth rate of tumor cells decreases with time

– Response to chemotherapy is during rapid growth phase.

• Gompertzian Model of Tumor Growth

– Growth rate of tumor cells decreases with time

– Response to chemotherapy is during rapid growth phase.

Time

Rapid rate of tumor growth

Plateau


• Goldie-Coldman Hypothesis

– A fraction of tumor cells will develop resistance after treatment.

– This clone will continue to grow even though the patient appears to respond.

– Alternating combinations of chemotherapy agents early in treatment is necessary to prevent development resistant clones.

• Goldie-Coldman Hypothesis

– A fraction of tumor cells will develop resistance after treatment.

– This clone will continue to grow even though the patient appears to respond.

– Alternating combinations of chemotherapy agents early in treatment is necessary to prevent development resistant clones.


• Worst-Drug Rule - Day

– Drug A works better than drug B against a tumor.

– Use Drug B first to shrink tumor.

– Use Drug A sequentially to overcome resistance.

– Assumes all tumors of resistant clones.

– Some tumors respond best to sequential therapy allowing for sparing of toxicity.

• Worst-Drug Rule - Day

– Drug A works better than drug B against a tumor.

– Use Drug B first to shrink tumor.

– Use Drug A sequentially to overcome resistance.

– Assumes all tumors of resistant clones.

– Some tumors respond best to sequential therapy allowing for sparing of toxicity.

Combination TherapyCombination Therapy

• Goals

– Maximum cell kill with tolerable toxicity

– Broad coverage of resistant cell lines

– Prevent development of resistance

• Method

– Use only effective drugs

– Use optimal scheduling and dose

– Limit overlapping toxicities

• Goals

– Maximum cell kill with tolerable toxicity

– Broad coverage of resistant cell lines

– Prevent development of resistance

• Method

– Use only effective drugs

– Use optimal scheduling and dose

– Limit overlapping toxicities

Combination TherapyCombination Therapy

• Disadvantages

– Multiple toxicities.

– Reduction or holding of doses due to toxicity will limit effectiveness.

– Complicated to administer.

– Expensive

• Disadvantages

– Multiple toxicities.

– Reduction or holding of doses due to toxicity will limit effectiveness.

– Complicated to administer.

– Expensive

Combination Therapy Toxicity Combination Therapy Toxicity -- CAFCAF

Toxicity Responsible Drug

Alopecia C, A

Cardiotoxicity A

Cystitis C

Mucositis A, F

Myelosuppression C,A,F

Toxicity Responsible Drug

Alopecia C, A

Cardiotoxicity A

Cystitis C

Mucositis A, F

Myelosuppression C,A,F

Factors Affecting Tumor ResponseFactors Affecting Tumor Response

• Tumor Burden• Tumor Site• Tumor Heterogeneity• Drug Resistance• Dose Intensity• Patient Specific Factors• Apoptosis

• Tumor Burden• Tumor Site• Tumor Heterogeneity• Drug Resistance• Dose Intensity• Patient Specific Factors• Apoptosis

Cell Cycle Specific DrugsCell Cycle Specific Drugs

• S Phase Specific Drugs– Antimetabolites

– Folate antagonists(methotrexate)

– Purine antagonists (cladribine)

– Pyrimidine antagonists (cytrarbine,fluorouracil)

• S Phase Specific Drugs– Antimetabolites

– Folate antagonists(methotrexate)

– Purine antagonists (cladribine)

– Pyrimidine antagonists (cytrarbine,fluorouracil)

Cell Cycle Specific DrugsCell Cycle Specific Drugs

• Mitosis Phase Specific Drugs– Vinca Alkaloids (vincristine, vinblastine)– Taxanes (paclitaxel, docetaxel)

• G2 Phase Specific Agents– Topoisomerase I Inhibitors (irinotecan)– Topoisomerase II Inhibitors (etoposide)

• G1 Phase Specific Agents– Enzymes (asparaginase)

• Mitosis Phase Specific Drugs– Vinca Alkaloids (vincristine, vinblastine)– Taxanes (paclitaxel, docetaxel)

• G2 Phase Specific Agents– Topoisomerase I Inhibitors (irinotecan)– Topoisomerase II Inhibitors (etoposide)

• G1 Phase Specific Agents– Enzymes (asparaginase)

Cell Cycle NonCell Cycle Non--Specific DrugsSpecific Drugs

• Alkylating Agents– Cyclophosphamide, busulfan

• Anthracyclines– Doxorubicin, daunorubicin, idarubicin

• Antibiotics– Mitomycin, dactinomycin

• Tryosine Kinase Inhibitors– Imatinib

• Alkylating Agents– Cyclophosphamide, busulfan

• Anthracyclines– Doxorubicin, daunorubicin, idarubicin

• Antibiotics– Mitomycin, dactinomycin

• Tryosine Kinase Inhibitors– Imatinib

Cell Cycle NonCell Cycle Non--Specific DrugsSpecific Drugs

• Biologic Agents– Immunomodulators (Interferon, Interleukin-2)

• Monoclonal Antibodies– Rituximab, Trastuzumab Gemtuzumab Ozogamicin,

Alemtuzumab, Ibritumomab Tiuxetan Yttrium-90, Cetuximab, Bevacizumab

• Hormones– Tamoxifen, leuprolide, flutamide

• Biologic Agents– Immunomodulators (Interferon, Interleukin-2)

• Monoclonal Antibodies– Rituximab, Trastuzumab Gemtuzumab Ozogamicin,

Alemtuzumab, Ibritumomab Tiuxetan Yttrium-90, Cetuximab, Bevacizumab

• Hormones– Tamoxifen, leuprolide, flutamide

Alkylating Agents Alkylating Agents

• Mechanism: Bind to DNA causing breaks• Cell Cycle Non-Specific• Major Toxicity: Myelosuppression, alopecia• Examples:

– Busulfan (Myleran)– Dacarbazine (DTIC)– Cyclophosphamide, Ifosfamide– Melphalan

• Mechanism: Bind to DNA causing breaks• Cell Cycle Non-Specific• Major Toxicity: Myelosuppression, alopecia• Examples:

– Busulfan (Myleran)– Dacarbazine (DTIC)– Cyclophosphamide, Ifosfamide– Melphalan

Busulfan ( Myleran)Busulfan ( Myleran)

IndicationsIndicationsDosingDosingRangeRange

Common Common ToxicitiesToxicities

1.8mg/m2PO daily or 0.06 mg/kg one time.

BMT: 4mg/kg/d PO3.2mg/kg/d IV

CMLCLLBMT

Myelosuppression Pulmonary fibrosisCNS Hepatic (VOD)

Dacarbazine (DTIC)Dacarbazine (DTIC)



250mg/m2x 5 days

SarcomaMelanoma

MyelosuppressionPhotosensitivityFlu-like symptomN/VIrritant Hepatic (vascular)VOD

Cyclophosphamide (Cytoxan)Cyclophosphamide (Cytoxan)



IV:500-2000mgper m2

Max: 100mg/kg/48H

PO:50-400mg/m2daily

ALLBreastCLLNHLHodgkins

MyelosuppressionN/VCardiac (HD)Hemm. CystitisSIADH

Ifosfamide (Ifex)Ifosfamide (Ifex)



1-2gm/m2daily x 4IV Only

SarcomaNHLOvarianTesticular

MyelosuppressionN/VHemm. Cystitis(Requires Mesna)CNS

Melphalan (Alkeran)Melphalan (Alkeran)



Oral: 9mg/m2Daily PO

BMT:50-140mg/m2 IV

Isolated LimbPerfusion: 0.8-1.5mg/kg

M.MyleomaBreast OvarianMelanoma

MyelosuppressionSecondary leukemiaPulmonary fibrosis

Other Alkylating AgentsOther Alkylating Agents

• Procarbazine(Matulane)

• Chlorambucil (Leukeran)

• Mechlorethamine (Mustargen)

• Procarbazine(Matulane)

• Chlorambucil (Leukeran)

• Mechlorethamine (Mustargen)

NitrosoureasNitrosoureas

• Mechanism: Bind to DNA causing breaks• Cell Cycle Non-Specific• Examples

– Carmustine (BCNU)– Lomustine (CeeNu)– Streptozocin (Zanosar)

• Mechanism: Bind to DNA causing breaks• Cell Cycle Non-Specific• Examples

– Carmustine (BCNU)– Lomustine (CeeNu)– Streptozocin (Zanosar)

Carmustine (BCNU)Carmustine (BCNU)



75-100mg/m2/dayx 2days

CNS TumorsSarcomaHodgkinsNHL

Delayed Myelosuppression(6 week nadir)N/VPulmonary fibrosis

Platinum AnaloguesPlatinum Analogues

• Mechanism: Form Crosslinks in DNA,RNA• Cell Cycle Non-Specific• Major Toxicity: Renal and N/V• Examples:

– Cisplatin (Platinol)– Carboplatin (Paraplatin)

• Mechanism: Form Crosslinks in DNA,RNA• Cell Cycle Non-Specific• Major Toxicity: Renal and N/V• Examples:

– Cisplatin (Platinol)– Carboplatin (Paraplatin)

Cisplatin (Platinol)Cisplatin (Platinol)



60-100 mg/m2I V q 21 days

LungTesticularHead & NeckBladderOvarian

Renal- hydrateElectrolyte AbnormalityN/V - SeverePeripheral NeuropathyOtotoxicity

Carboplatin ( Paraplatin)Carboplatin ( Paraplatin)



300-400mg/m2 IVorAUC Dose5-7mg/mlxminDose = AUC(CrCl+25)

LungTesticularHead & NeckBreastBladderOvarian

MyelosuppressionN/VCNS Hypersensitivity

Oxaliplatin (Eloxatin®)Oxaliplatin (Eloxatin®)



85mg/m2 IVover 2 hoursevery 2 weekscombined with5FU+ LV

Colon 90% NeuropathyMyelosuppression

AnthracyclinesAnthracyclines

• Mechanism: Intercalate DNA base pairs• Cell Cycle Non-Specific• Major Toxicity: Cardiac, Vesicant, Alopecia• Examples:

– Doxorubicin (Adriamycin)– Daunorubicin (Cerubidine)– Idarubicin (Idamycin)– Epirubicin (Ellence)– Mitoxantrone (Novantrone)

• Mechanism: Intercalate DNA base pairs• Cell Cycle Non-Specific• Major Toxicity: Cardiac, Vesicant, Alopecia• Examples:

– Doxorubicin (Adriamycin)– Daunorubicin (Cerubidine)– Idarubicin (Idamycin)– Epirubicin (Ellence)– Mitoxantrone (Novantrone)

Doxorubicin (Adriamycin)Doxorubicin (Adriamycin)



60-100mg/m2 IV Q21 days

MAX:450mg/m2with XRT300mg/m2

BreastBladderNHLHodgkinsSarcomaMyelomaLungAML

MyelosuppressionCardiac ToxicityN/VMucositisVesicant

Daunorubicin (Cerubidine)Daunorubicin (Cerubidine)



30-60mg/m2/dayx3-5 days

MAX:550mg/m2in adults

AMLALLNHLWilm’s TumorNeuroblastoma

MyelosuppressionCardiac ToxicityN/VMucositisVesicant

Idarubicin (Idamycin)Idarubicin (Idamycin)



12 mg/m2/dayx 3 days

MAX:120mg/m2

AMLALL

MyelosuppressionN/VCardiacVesicant

Epirubicin (Ellence)Epirubicin (Ellence)



IV:60-100mg/m2IVP MAX:700mg/m2

Breast CardiacMyelosuppressionN/VAlopeciaVesicant

Mitoxantrone ( Novantrone )Mitoxantrone ( Novantrone )



12 mg/m2/dayx 3-5 days forAML12mg/m2 IVQ 21 daysfor solid tumors.MAX:160mg/m2

AMLNHLBreast

MyelosuppressionMucositisN/VCardiac

CardiotoxicityCardiotoxicity

Agent EKGCHG

Arrhythmia CHF Myopathy

DoxorubicinDaunorubici

++ ++ +++ +++

Idarubicin ++ ++ ++ ++Epirubicin + + ++ ++Mitoxantrone + ++ +CytoxanIfosfamide

++ ++

Paclitaxel ++ ++

Agent EKGCHG

Arrhythmia CHF Myopathy

DoxorubicinDaunorubici

++ ++ +++ +++

Idarubicin ++ ++ ++ ++Epirubicin + + ++ ++Mitoxantrone + ++ +CytoxanIfosfamide

++ ++

Paclitaxel ++ ++

AntibioticsAntibiotics

• Mechanism: DNA breakage• Cell Cycle Non-Specific• Major Toxicity: Pulmonary and Renal• Examples:

– Mitomycin– Bleomycin

• Mechanism: DNA breakage• Cell Cycle Non-Specific• Major Toxicity: Pulmonary and Renal• Examples:

– Mitomycin– Bleomycin

Mitomycin (Mutamycin)Mitomycin (Mutamycin)



10-20mg/m2 Q6 weeksMAX: 60mg/m2 Total

BladderBreastLung

MyelosuppressionHUS(dose related)Pulmonary(avoid high O2 levels)Vesicant

Bleomycin (Blenoxane)Bleomycin (Blenoxane)



10-20 U/m2IV or IM 1-2 x per week

Pleurodesis:60 unitsMAX:400 U Total

TesticularNHLMalignantPleuralEffusions

Pulmonary fibrosis(avoid high O2 levels)AnaphylaxisFeverHyperpimentation

Pulmonary ToxicityPulmonary Toxicity

• Bleomycin– Avoid high 02 concentrations for several weeks post chemo– Incidence is 1-3% when doses >400 units– Symptoms include dyspnea and dry cough

• Carmustine– 20-30% lung fibrosis with doses >600mg/m2

• Mitomycin C– Incidence 3-12% when doses exceed 60 mg

• Busulfan– Incidence of fibrosis 3% when >500mg

• Bleomycin– Avoid high 02 concentrations for several weeks post chemo– Incidence is 1-3% when doses >400 units– Symptoms include dyspnea and dry cough

• Carmustine– 20-30% lung fibrosis with doses >600mg/m2

• Mitomycin C– Incidence 3-12% when doses exceed 60 mg

• Busulfan– Incidence of fibrosis 3% when >500mg

Antimetabolites: Folate AntagonistsAntimetabolites: Folate Antagonists

• Mechanism: Blocks tetrahydrofolic acid production

• Cell Cycle Specific: S Phase• Major Toxicity: Myelosuppression & GI• Example

– Methotrexate– Edatrexate– Pemetrexed

• Mechanism: Blocks tetrahydrofolic acid production

• Cell Cycle Specific: S Phase• Major Toxicity: Myelosuppression & GI• Example

– Methotrexate– Edatrexate– Pemetrexed

Methotrexate (Mexate, MTX)Methotrexate (Mexate, MTX)



Low:10-100mg/m2Inter: 1-2 g/m2High:10-12 g/m2Intrathecal:12mg

BreastNHLSarcomaALL

MyelosuppressionMucositisRadiation SensitizerRenal- alkalinize urineCNS

(Leucovorin Rescue)

Pemetrexed ( Alimta)Pemetrexed ( Alimta)



500mg/m2Every 21 days

Requires FolicAcid and B12Supplements

MesotheliomaNSCLC

Neutropenia 24%N/V 30%Fatigue 25%

Antimetabolites: Pyrimidine AntagonistsAntimetabolites: Pyrimidine Antagonists

• Mechanism: Block DNA production• Cell Cycle Specific: S Phase• Major Toxicity: Myelosuppression • Examples

– Cytarabine– Fluorouracil– Capecitabine– Gemcitabine


– Cytarabine– Fluorouracil– Capecitabine– Gemcitabine

Cytarabine ( Cytosar, AraCytarabine ( Cytosar, Ara--C)C)



100-200mg/m2/dayx 5-7 daysCIVI 1-3 g/m2 Q12 hrs bolus10-30mg/m2intrathecal

AMLALLCMLNHL

MyelosuppressionCerebellar (High Dose)Ocular (High Dose)PulmonaryHepatic (VOD)

Fluorouracil (5Fluorouracil (5--FU, Adrucil)FU, Adrucil)



IV:400 - 500mg/m2 weekly

300-1000mg/m2/dayx 5-7 days

ColonBreastHead & NeckGastric

MyelosuppressionMucositis (CIVI)DiarrheaCardiacRashCNS

Capecitabine (Xeloda)Capecitabine (Xeloda)



Oral:1250mg/m2BID x 14 daysWith 1-2 weekrest

BreastColon

DiarrheaHand/Foot Syndrome

Gemcitabine (Gemzar)Gemcitabine (Gemzar)



IV:1000mg/m2over 30 minweekly X 3

PancreaticBreastLung

MyelosuppressionN/VRashHepatic

Antimetabolites: Purine AntagonistsAntimetabolites: Purine Antagonists


– Cladribine– Fludarabine– Mercaptopurine


– Cladribine– Fludarabine– Mercaptopurine

Cladribine (2Cladribine (2--CDA, Leustatin)CDA, Leustatin)



0.1mg/kgdaily x 7CIVI

Hairy CellLeukemiaNHLCLLWaldenstrom

MyelosuppressionFeverRash

Fludarabine (Fludara)Fludarabine (Fludara)



IV:25mg/m2daily x 5

NHLCLLAML

MyelosuppressionEncephalopathyPulmonary

Mercaptopurine (Purinethol, 6Mercaptopurine (Purinethol, 6--MP)MP)



PO:70-100mg/m2or 2.5mg/kgdaily

HodgkinsALLCMLNHLAML

MyelosuppressionHepatic (VOD)

Interacts withAllopurinol

Vinca AlkaloidsVinca Alkaloids

• Mechanism: Inhibits spindle formation• Cell Cycle Specific: M Phase• Major Toxicity: Neuropathy, alopecia, vesicants• Examples

– Vincristine– Vinblastine– Vinorelbine

• Mechanism: Inhibits spindle formation• Cell Cycle Specific: M Phase• Major Toxicity: Neuropathy, alopecia, vesicants• Examples

– Vincristine– Vinblastine– Vinorelbine

Vincristine (Oncovin)Vincristine (Oncovin)



IV:0.4-1.4mg/m2weeklyMAX: 2mgweekly

ALLNHLCLLBreastHodgkinsNeuroblastoma

NeuropathyConstipationIleusVesicantSIADH

DEATH with overdoseor intrathecal use

Vinblastine (Velban)Vinblastine (Velban)



IV:4-10mg/m2weekly

HodgkinsNHLCMLBreast

MyelosuppressionNeuropathyVesicant

Vinorelbine (Navelbine)Vinorelbine (Navelbine)



IV30mg/m2weekly

BreastNSCLCOvarian

MyelosuppressionNeuropathyConstipationSIADHVesicant (flush vein)

Vesicants Vesicants IrritantsIrritants

• Dactinomycin• Daunorubicin• Doxorubicin• Epirubicin• Idarubicin• Mechlorethamine• Mitomycin C• Dactinomycin • Vincristine• Vinblastine• Vinorelbine

• Dactinomycin• Daunorubicin• Doxorubicin• Epirubicin• Idarubicin• Mechlorethamine• Mitomycin C• Dactinomycin • Vincristine• Vinblastine• Vinorelbine

• Cisplatin

• Carboplatin

• Docetaxel

• Etoposide

• Mitoxantrone

• Paclitaxel

• Teniposide

• Cisplatin

• Carboplatin

• Docetaxel

• Etoposide

• Mitoxantrone

• Paclitaxel

• Teniposide

ExtravasationExtravasation

Treatment of ExtravasationsTreatment of Extravasations

• Stop Infusion• Leave catheter in place• Remove tubing• Aspirate as much as possible from site• Instill antidote if indicated• Remove needle• Inject SQ antidote into site in 3-6 areas around site

– Sodium thiosulfate 1/6 M for mechlorethamine,cisplatin, carboplatin– Hyaluronidase 150-900 units for vinca alkaloids

• Apply cold compress 45 minutes on 15 min off for 24 hr• Apply warm compress for vincas, etoposide and taxanes

• Stop Infusion• Leave catheter in place• Remove tubing• Aspirate as much as possible from site• Instill antidote if indicated• Remove needle• Inject SQ antidote into site in 3-6 areas around site

– Sodium thiosulfate 1/6 M for mechlorethamine,cisplatin, carboplatin– Hyaluronidase 150-900 units for vinca alkaloids

• Apply cold compress 45 minutes on 15 min off for 24 hr• Apply warm compress for vincas, etoposide and taxanes

Topoisomerase Topoisomerase I Inhibitors:I Inhibitors:CamptothecinsCamptothecins• Mechanism: Inhibit Topoisomerase I• Cell Cycle Specific: G2 Phase• Major Toxicity:Diarrhea,Myelosuppression• Examples

– Irinotecan– Topotecan

• Mechanism: Inhibit Topoisomerase I• Cell Cycle Specific: G2 Phase• Major Toxicity:Diarrhea,Myelosuppression• Examples

– Irinotecan– Topotecan

Irinotecan Irinotecan ((CamptosarCamptosar, CPT, CPT--11)11)



IV: 125mg/m2 weekly x 4 Or 350mg/m2Q 21 days

ColonSCLCPancreaticGastric

Diarrhea(Loperamide)MyelosuppressionFlushingN/VAlopecia

Topotecan Topotecan ((HycamtinHycamtin))



1.5mg/m2daily x5

LungOvarian

MyelosuppressionDiarrheaHeadache

DiarrheaDiarrhea

• Causative agents

– Irinotecan

– Topotecan

– Cytarabine

– Fluorouracil

– Methotrexate

– Gemcitabine

• Causative agents

– Irinotecan

– Topotecan

– Cytarabine

– Fluorouracil

– Methotrexate

– Gemcitabine

• Treatment

– Loperamide

– Octreotide

• Treatment

– Loperamide

– Octreotide

Topoisomerase Topoisomerase II Inhibitors:II Inhibitors:EpipodophyllotoxinsEpipodophyllotoxins• Mechanism: Inhibit Topoisomerase II• Cell Cycle Specific: G2 Phase• Major Toxicity: Myelosuppression,

Mucositis• Examples

– Etoposide– Teniposide

• Mechanism: Inhibit Topoisomerase II• Cell Cycle Specific: G2 Phase• Major Toxicity: Myelosuppression,

Mucositis• Examples

– Etoposide– Teniposide

Etoposide Etoposide ((VepesidVepesid))



IV:30-120mg/m2/dayx 1-5 daysPO:50% Absorbed.50-100mg/m2 daily

LungNHLBreastAMLALL

MyelosuppressionMucositisAlopecia Infusion-related:Hypotension

Teniposide Teniposide ((VumonVumon))



IV:ALL:165mg/m2twice a week

Solid Tumors:60-90mg/m2

ALLNeuroblastomaNHL

MyelosuppressionMucositis

TaxanesTaxanes

• Mechanism: Stabilizes Microtubules• Cell Cycle Specific: M Phase• Major Toxicity: Myelosuppression,

Neuropathy, Allergic Reactions, Alopecia• Examples

– Paclitaxel– Docetaxel

• Mechanism: Stabilizes Microtubules• Cell Cycle Specific: M Phase• Major Toxicity: Myelosuppression,

Neuropathy, Allergic Reactions, Alopecia• Examples

– Paclitaxel– Docetaxel

Paclitaxel Paclitaxel ((TaxolTaxol))



IV:135-250mg/m2Q21 daysor80mg/m2weekly

BreastLungOvarianHead & NeckBladder

MyelosuppressionHypersensitivityNeuropathyMyalgiaAlopecia

Docetaxel Docetaxel ((TaxotereTaxotere))



60-100mg/m2Q 21 days

BreastLungH+NOvarian

MyelosuppressionPleural EffusionsPeripheral EdemaAngioedemaHypersensitivityMucositisAlopecia

ImmunomodulatorsImmunomodulators

• Mechanism: Enhance immune function• Cell Cycle Non- Specific • Major Toxicity:Myalgia, hypotension• Examples

– Interferon– Aldesleukin (IL-2)

• Mechanism: Enhance immune function• Cell Cycle Non- Specific • Major Toxicity:Myalgia, hypotension• Examples

– Interferon– Aldesleukin (IL-2)

Interferon (Interferon (Roferon Roferon A, A, Intron Intron A)A)



IM or SQ:3-10 MillionUnits 3 timesa week.

MelanomaCML

Flu SymptomsMyalgiaFeverN/V, AnorexiaDepressionCough

Aldesleukin Aldesleukin ( ( ProleukinProleukin, IL, IL--2)2)



IV: High-dose600,000 Units/Kg Q 8 HrsLow-dose2million/m2daily x 4 as CIVI

Renal CellMelanoma

Hypotension ( with high dose) Fever, chills Edema, EffusionsLiver Toxocity

Monoclonal AntibodiesMonoclonal Antibodies

• Mechanism: Destroy specific cells with antigenic markers

• Cell Cycle Non- Specific • Major Toxicity: Infusion-related toxicity• Examples:

– Rituximab– Trastuzumab– Gemtuzumab Ozogamicin– Alemtuzumab– Ibritumomab Tiuxetan Yttrium-90– Cetuximab– Bevacizumab

• Mechanism: Destroy specific cells with antigenic markers

• Cell Cycle Non- Specific • Major Toxicity: Infusion-related toxicity• Examples:

– Rituximab– Trastuzumab– Gemtuzumab Ozogamicin– Alemtuzumab– Ibritumomab Tiuxetan Yttrium-90– Cetuximab– Bevacizumab

Rituximab Rituximab ( ( RituxanRituxan))



IV:375mg/m2slowly Q week

NHL(CD-20 +)

Fever, chills(1st infusion worst)HypotensionBronchospasmTLS (large tumor)

TrastuzumabTrastuzumab ((HerceptinHerceptin))



IV:Load: 4mg/kgover 90 min.

Maint: 2mg/kgover 30 min.Q week

Breast(Her-2 overexpression)

Fever, Chills(1st Infusion)Cardiac (CHF)√ MUGAN/V, DiarrheaRash

Gemtuzumab Ozogamicin Gemtuzumab Ozogamicin ((MylotargMylotarg))



IV:9mg/m2 over 2 hourson Day 1 and15.

AML for patients>60 year

Fever, Chills,Hypotension,Neutropenia, Thrombocytopenia,Anemia,Tumor Lysis

Alemtuzumab Alemtuzumab ((CampathCampath))



IV:3mg IV dailyover 2 hoursthen 10mg daily,then 30mg 3x a week

Anti CD-52B-cell CLLfailed Fludarabine

Fever, Chills,Hypotension,Neutropenia, Thrombocytopenia,Anemia,Tumor LysisHSV AND PCP x 2months

Ibritumomab Tiuxetan Ibritumomab Tiuxetan YY--90 (90 (ZevalinZevalin))RadioimmunotherapyRadioimmunotherapy



IV:0.3 -0.4mCi/kgonce

Refractorylow-grade CD20+NHL

Neutropenia 63%, Thrombocytopenia 60%,Anemia 17%

CetuximabCetuximab ((ErbituxErbitux))



IV:400mg/m2Over 2 hrs x1, Then250mg/m2 Over 1 hrWeekly.

EGFR +ColorectalIrinotecan refractory

Infusion Reaction 3%Bronchospasm, AnaphylaxisInter. Lung Dis. 1%Severe Acne 14%Fever 5%

Bevacizumab Bevacizumab ((AvastinAvastin))



IV:5mg/kg Over 90 min.every14 days.

MetastaticColorectalAnti-VEGF

Infusion ReactionsGI Perforation 2%HemorrhageNephrotic SyndromeCHF 14%Neutropenia 21%Hypertension 60%

Tyrosine Tyrosine Kinase Kinase InhibitorInhibitor

• Mechanism: Inhibits tyrosine kinase regulation of cell growth

• Cell Cycle Non- Specific • Major Toxicity: Variable• Examples:

– Imatinib– Erlotinib

• Mechanism: Inhibits tyrosine kinase regulation of cell growth

• Cell Cycle Non- Specific • Major Toxicity: Variable• Examples:

– Imatinib– Erlotinib

ImatinibImatinib ( ( GleevecGleevec))



PO: 400 -800mg daily

CML: Ph +,chronic,acceleratedphases,and blast crisis

Neutropenia 33-60%Thrombocytopenia 16- 60%Anemia 4-50%Hepatotoxicity 1-3%Fluid Retention1-5%

ErlotinibErlotinib ((TarcevaTarceva))



PO: 100-150mg daily

NSCLCPancreatic

Interstitial Lung Disease 1%Hepatotoxicity RashFatigue

Hormonal AgentsHormonal Agents• Mechanism: Block or prevent hormonal

effects on tumor cells• Cell Cycle Non- Specific • Major Toxicity: Hormonal dysfunction• Examples:

– Tamoxifen – Leuprolide– Bicalutimide

• Mechanism: Block or prevent hormonal effects on tumor cells

• Cell Cycle Non- Specific • Major Toxicity: Hormonal dysfunction• Examples:

– Tamoxifen – Leuprolide– Bicalutimide

Tamoxifen (Nolvadex)Tamoxifen (Nolvadex)



PO:10-20mg POBID

Breast Hot FlashesN/VFlare ReactionVTECategory D:PRF

AnastrazoleAnastrazole ((ArimidexArimidex))



PO:1mg daily

Breast Hot FlashesN/VFlare ReactionVTEPreg Category D:

Leuprolide (Lupron)Leuprolide (Lupron)



IM:7.5mg monthly or 22.5mg q3months

Prostate Hot flashesImpotenceDecreased LibidoTumor Flare

FlutamideFlutamide ((EulexinEulexin ))



PO:250mg tid

Prostate HepatotoxicityGynecomastiaDiarrheaMyalgia

BicalutamideBicalutamide ((CasodexCasodex))



PO:50-150 mg daily

Prostate HepatotoxicityGynecomastiaDiarrheaMyalgia

Calculations:Calculations:

Height (cm) x Weight (Kg)3600

BSA (m2) =

Body Surface AreaBody Surface Area

Estimated Estimated Creatinine Creatinine ClearanceClearanceGFR Males = (140-age) x Weight ( Kg)

72 x SCrGFR Females = GFR Males X 0.85