Clinical Division of Oncology Department of Medicine I Mediacal University of Vienna, Austria...

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Clinical Division of Oncology Department of Medicine I Mediacal University of Vienna, Austria Principles of chemotherapy

Transcript of Clinical Division of Oncology Department of Medicine I Mediacal University of Vienna, Austria...

Page 1: Clinical Division of Oncology Department of Medicine I Mediacal University of Vienna, Austria Principles of chemotherapy.

Clinical Division of OncologyDepartment of Medicine I

Mediacal University ofVienna, Austria

Principles of chemotherapy

Page 2: Clinical Division of Oncology Department of Medicine I Mediacal University of Vienna, Austria Principles of chemotherapy.

Clinical Division of OncologyDepartment of Medicine I

Mediacal University ofVienna, Austria

Principles of chemotherapy Stages of Mitosis

Interphase

ProphaseDaughter cells

Telophase

Anaphase

Metaphase

Page 3: Clinical Division of Oncology Department of Medicine I Mediacal University of Vienna, Austria Principles of chemotherapy.

Clinical Division of OncologyDepartment of Medicine I

Mediacal University ofVienna, Austria

Principles of chemotherapy Electron micrograph of Electron micrograph of

mitotic cellmitotic cell

Page 4: Clinical Division of Oncology Department of Medicine I Mediacal University of Vienna, Austria Principles of chemotherapy.

Clinical Division of OncologyDepartment of Medicine I

Mediacal University ofVienna, Austria

Principles of chemotherapy Classification of cytotoxic agentsClassification of cytotoxic agents

Busulfan Cytosine Etoposide Bleomycin L-asparaginase

Carmustine Arabinoside Teniposide Dactinomycin Hydroxyurea

Chlorambucil Floxuridine Vinblastine Daunorubicin Procarbazine

Cisplatin Fluorouracil Vincristine Doxorubicin

Cyclophosphamide Mercaptopurine Vindesine Mitomycin-c

Ifosfamide Methotrexate Taxoids Mitoxantrone

Melphalan Plicamycin

AlkylatingAlkylating

AgentsAgents

Anti-Anti-

MetabolitesMetabolites

MitoticMitotic

InhibitorsInhibitorsAntibioticsAntibiotics OthersOthers

Page 5: Clinical Division of Oncology Department of Medicine I Mediacal University of Vienna, Austria Principles of chemotherapy.

Clinical Division of OncologyDepartment of Medicine I

Mediacal University ofVienna, Austria

Principles of chemotherapy Action sites of cytotoxic agentsAction sites of cytotoxic agents

Antibiotics

Antimetabolites

S(2-6h)

G2

(2-32h)

M(0.5-2h)

Alkylating agents

G1

(2-h)

G0

Vinca alkaloids

Mitotic inhibitors

TaxoidsCell cycle levelCell cycle level

Page 6: Clinical Division of Oncology Department of Medicine I Mediacal University of Vienna, Austria Principles of chemotherapy.

Clinical Division of OncologyDepartment of Medicine I

Mediacal University ofVienna, Austria

Principles of chemotherapy Action sites of cytotoxic agentsAction sites of cytotoxic agents

DNA synthesis

AntimetabolitesAntimetabolites

DNA

DNA transcription DNA duplication

Mitosis

Alkylating agentsAlkylating agents

Spindle poisonsSpindle poisons

Intercalating agentsIntercalating agents

Cellular levelCellular level

Page 7: Clinical Division of Oncology Department of Medicine I Mediacal University of Vienna, Austria Principles of chemotherapy.

Clinical Division of OncologyDepartment of Medicine I

Mediacal University ofVienna, Austria

Principles of chemotherapy Action sites of cytotoxic agentsAction sites of cytotoxic agents

6-MERCAPTOPURINE

6-THIOGUANINE

METHOTREXATE

5-FLUOROURACIL

HYDROXYUREA

CYTARABINE

PURINE SYNTHESISPURINE SYNTHESIS PYRIMIDINE SYNTHESISPYRIMIDINE SYNTHESIS

RIBONUCLEOTIDESRIBONUCLEOTIDES

DEOXYRIBONUCLEOTIDESDEOXYRIBONUCLEOTIDES

DNADNA

RNARNA

PROTEINSPROTEINS

MICROTUBULESMICROTUBULESENZYMESENZYMES

L-ASPARAGINASEVINCA ALKALOIDS

TAXOIDS

ALKYLATING AGENTS

ANTIBIOTICS

ETOPOSIDE

Page 8: Clinical Division of Oncology Department of Medicine I Mediacal University of Vienna, Austria Principles of chemotherapy.

Clinical Division of OncologyDepartment of Medicine I

Mediacal University ofVienna, Austria

Principles of chemotherapy Metabolism of cytotoxic agentsMetabolism of cytotoxic agents

CYCLOPHOSPHAMIDECYCLOPHOSPHAMIDE

4-OH CYCLOPHOSPHAMIDE4-OH CYCLOPHOSPHAMIDE

ALDOPHOSPHAMIDEALDOPHOSPHAMIDE

PHOSPHORAMIDEPHOSPHORAMIDE

MUSTARDMUSTARD

4-KETOCYCLOPHOSPHAMIDE4-KETOCYCLOPHOSPHAMIDE

CARBOXYPHOSPHAMIDECARBOXYPHOSPHAMIDE

ACROLEINACROLEIN

HEPATICHEPATICCYTOCHROMESCYTOCHROMES

P 450P 450ACTIVATIONACTIVATION

CYTOTOXICITYCYTOTOXICITYTOXICITYTOXICITY

INACTIVATIONINACTIVATION

ALDEHYDEALDEHYDE

DEHYDROGENASEDEHYDROGENASE

Cyclophosphamide

Page 9: Clinical Division of Oncology Department of Medicine I Mediacal University of Vienna, Austria Principles of chemotherapy.

Clinical Division of OncologyDepartment of Medicine I

Mediacal University ofVienna, Austria

Principles of chemotherapy

Drug resistanceDrug resistanceEXTRACELLULAREXTRACELLULAR INTRACELLULARINTRACELLULAR

ATPATP

PGPPGP170170 ATPATP

DrugDrug

DrugDrug

PlasmaPlasmaMembraneMembrane

Page 10: Clinical Division of Oncology Department of Medicine I Mediacal University of Vienna, Austria Principles of chemotherapy.

Clinical Division of OncologyDepartment of Medicine I

Mediacal University ofVienna, Austria

Principles of chemotherapy Aim of combination therapyAim of combination therapy

INCREASED EFFICACYINCREASED EFFICACY

Different mechanisms of action Compatible side effects

Different mechanisms of resistance

ACTIVITYACTIVITY SAFETYSAFETY

Page 11: Clinical Division of Oncology Department of Medicine I Mediacal University of Vienna, Austria Principles of chemotherapy.

Clinical Division of OncologyDepartment of Medicine I

Mediacal University ofVienna, Austria

Principles of chemotherapy Side effects of chemotherapySide effects of chemotherapy

Alopecia

Pulmonary fibrosis

Cardiotoxicity

Local reaction

Renal failure

Myelosuppression

Phlebitis

Mucositis

Nausea/vomiting

Diarrhea

Cystitis

Sterility

Myalgia

Neuropathy


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