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Principles  of  Systemic Therapy in  Cancer N. PAVLIDIS PROFESSOR  OF  MEDICAL  ONCOLOGY  UNIVERSITY  OF  IOANNINA  GREECE ESO  COURSE IOANNINA,  JULY 2011
Principles  of   … ,[object Object],[object Object],[object Object],[object Object]
INTRODUCTION  TO   CHEMOTHERAPY
ALKYLATING  AGENTS Mechanism  of action : Target DNA, produce alkylation through formation of intermediates. No phase-specific drugs Busulfan  Chlorambucil  Cisplatin, Carboplatin, Oxaliplatin Cyclophosphamide, Ifosfamide Dacarbazine Mechlorethamine (Nitrogen Mustard) Melphalan Nitrosoureas Procarbazine Streptozotocin  Temozolomide Thiotepa
ANTIMETABOLITES Mechanism  of action   : Interfere with DNA synthesis. They are structural analogs or they inhibit several enzymes. S-phase specific Aracytidine Cytarabin Fludarabine Fluorouracil Leucovorin Capecitabine Gemcitabine  Hydroxyurea Mercaptopurine Methotrexate Pemetrexed Pentostatin Raltitrexed Thioguanine Trimetrexate Uracil / Tegafur (UFT)
ANTITUMOR  ANTIBIOTICS Mechanism of action  : A variety of mechanisms. They are derived from microorganisms. Cell cycle specific drugs Actinomycin-D Bleomycin Daunorubicin Doxorubicin Doxorubicin Liposomal Epirubicin Idarubicin Mitomycin Mitoxantrone
MITOTIC  SPINDLE  AGENTS Mechanism of action : Bind to microtubular proteins, thus inhibit microtubule assembly resulting in dissolution of the mitotic assembly structure. M- phase specific drugs. Docetaxel Paclitaxel Vinblastine Vincristine Vindesine Vinorelbine
TOPOISOMERASE  INHIBITORS Mechanism of action : DNA Topoisomerases I and II are essential enzymes for transcription, replication and mitosis. The following drugs are able to inhibit these enzymes.  Topoisomerease  I  inhibitors Irinotecan  Topotecan Topoisomerase  II inhibitors Etoposide  Teniposide
MISCELLANEOUS  AGENTS Asparaginase  Estramustine Hexamethymelamine Octreotide Velcade
MODES  OF  CHEMOTHERAPY  ADMINISTRATION ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
PRINCIPLES  OF  COMBINATION  CHEMOTHERAPY ,[object Object],[object Object],[object Object],[object Object],[object Object]
SYSTEMIC  CHEMOTHERAPY  NEOADJUVANT  CHEMOTHERAPY  [PREOPERATIVELY] Rationale  ,[object Object],[object Object],[object Object],ADJUVANT  CHEMOTHERAPY  [POSTOPERATIVELY] Rationale  ,[object Object],[object Object],THERAPY  FOR  METASTATIC  DISEASE Rationale  ,[object Object],[object Object]
CHEMOTHERAPY  CAN  ALSO  BE  GIVEN  AS :  ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
PARAMETERS  TO  BE  EVALUATED  IN  SYSTEMIC  TREATMENTS   ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],R ESPONSE
[object Object],[object Object],PARAMETERS  TO  BE  EVALUATED  IN  SYSTEMIC  TREATMENTS   S URVIVAL
 
CHEMOTHERAPY  TOXICITIES   ( I ) Bone  m arrow  s uppression   (anemia, leucopenia,  thrombocytopenia) Almost all Erythropoietin, G-CSF, blood transfusions TOXICITY DRUG  INDUCED ANTIDOTE Nausea- v omiting Platinum Anthracyclines Alkylating s Centrones   (serotonin block):  granisetron ,  ondasetron Alopecia Anthracyclines Taxanes Scalp-cooling techniques  (not universally accepted) Cardiotoxicity Anthracyclines Cyclophosphamide 5-FU Early  detection .  Dexrazoxane
CHEMOTHERAPY  TOXICITIES   ( II ) Pulmonary  toxicity Bleom y c i n Alkylating s Gemcitabine Early   detection .  Corticosteroids Nephrotoxicity Platinum Methotrexate   (↑dose) Adequate  hydration Neurotoxicity Alkaloids Platinum Taxanes Early  detection Gonadal  d amage Alkylatings Others Sperm   preservation Second  m alignancies Alkylating s Avoid  if  possible  responsible drugs and/or  RT   in   curable  diseases
INTRODUCTION  TO  ENDOCRINE  THERAPY  (HORMONAL  AGENTS)
Endocrine  therapy ,[object Object],[object Object],[object Object]
ANTIESTROGENS ,[object Object],[object Object],[object Object],[object Object],[object Object],Mechanism  of action :  Occupy  estrogen  receptors. ANTIESTROGENS
[object Object],[object Object],[object Object],Mechanism  of action : Occupy  progesterone receptors . PROGESTINS
AROMATASE   INHIBITORS ,[object Object],[object Object],[object Object],[object Object],Mechanism of action  : Reduce estrogen levels by interfering with aromatase which converts androstendione to estrone and then to estradiol
LUTEINIZING  HORMONE –  RELEASING  HORMONE (LHRH  AGONISTS)   ,[object Object],[object Object],[object Object],[object Object],Mechanism of action : Reduce estrogen levels by inhibiting gonadotrophin release from the pituitary
ANTIANDROGENS  ,[object Object],[object Object],[object Object],[object Object],Mechanism of action : Inhibit the uptake and binding of androgens in target tissues.
[object Object],[object Object]
CYTOKINES ,[object Object],[object Object],[object Object],[object Object],Mechanisms  of action  :  Activation of NK cells, of cytotoxic T-lymphocytes, induction of MHC class I, antiviral, antitumor and antiproliferative activities.
[object Object],[object Object]
 
MONOCLONAL  ANTIBODIES ,[object Object],[object Object],Mechanism  of  action :  Attack certain cell targets RITUXIMAB  (Mabthera)
[object Object],HER-2 :   17%-30% TRASTUZUMAB  (Herceptin) ,[object Object]
[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],BEVACIZUMAB  (Avastin)
[object Object],[object Object],[object Object],CETUXIMAB  (Erbitux)
SMALL  MOLECULES  AND INTRACELLULAR  SIGNAL  TRANSDUCTION  TYROSINE  KINASE  INHIBITORS
[object Object],[object Object],[object Object],[object Object],IMATINIB   (Gleevec)
ERLOTINIB  (Tarceva)   / GEFITINIB  (Iressa) Invasion Metastasis Growth Factor Secretion B1 B1 Cell Membrane Nucleus TKI  Antibody ,[object Object],[object Object],Anti-Apoptosis Proliferation
[object Object],[object Object],[object Object],SUNITINIB  (Sutent)
[object Object],[object Object],SORAFENIB  (Nexavar)
[object Object],[object Object],[object Object],TEMSIROLIMUS  (Torisel)
[object Object],[object Object],[object Object],LAPATINIB  (Tykerb)
[object Object]

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Medical Students 2011 - N. Pavlidis - INTRODUCTION TO CANCER TREATMENT- Basics in Systemic Treatment

  • 1. Principles of Systemic Therapy in Cancer N. PAVLIDIS PROFESSOR OF MEDICAL ONCOLOGY UNIVERSITY OF IOANNINA GREECE ESO COURSE IOANNINA, JULY 2011
  • 2.
  • 3. INTRODUCTION TO CHEMOTHERAPY
  • 4. ALKYLATING AGENTS Mechanism of action : Target DNA, produce alkylation through formation of intermediates. No phase-specific drugs Busulfan Chlorambucil Cisplatin, Carboplatin, Oxaliplatin Cyclophosphamide, Ifosfamide Dacarbazine Mechlorethamine (Nitrogen Mustard) Melphalan Nitrosoureas Procarbazine Streptozotocin Temozolomide Thiotepa
  • 5. ANTIMETABOLITES Mechanism of action : Interfere with DNA synthesis. They are structural analogs or they inhibit several enzymes. S-phase specific Aracytidine Cytarabin Fludarabine Fluorouracil Leucovorin Capecitabine Gemcitabine Hydroxyurea Mercaptopurine Methotrexate Pemetrexed Pentostatin Raltitrexed Thioguanine Trimetrexate Uracil / Tegafur (UFT)
  • 6. ANTITUMOR ANTIBIOTICS Mechanism of action : A variety of mechanisms. They are derived from microorganisms. Cell cycle specific drugs Actinomycin-D Bleomycin Daunorubicin Doxorubicin Doxorubicin Liposomal Epirubicin Idarubicin Mitomycin Mitoxantrone
  • 7. MITOTIC SPINDLE AGENTS Mechanism of action : Bind to microtubular proteins, thus inhibit microtubule assembly resulting in dissolution of the mitotic assembly structure. M- phase specific drugs. Docetaxel Paclitaxel Vinblastine Vincristine Vindesine Vinorelbine
  • 8. TOPOISOMERASE INHIBITORS Mechanism of action : DNA Topoisomerases I and II are essential enzymes for transcription, replication and mitosis. The following drugs are able to inhibit these enzymes. Topoisomerease I inhibitors Irinotecan Topotecan Topoisomerase II inhibitors Etoposide Teniposide
  • 9. MISCELLANEOUS AGENTS Asparaginase Estramustine Hexamethymelamine Octreotide Velcade
  • 10.
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  • 16.  
  • 17. CHEMOTHERAPY TOXICITIES ( I ) Bone m arrow s uppression (anemia, leucopenia, thrombocytopenia) Almost all Erythropoietin, G-CSF, blood transfusions TOXICITY DRUG INDUCED ANTIDOTE Nausea- v omiting Platinum Anthracyclines Alkylating s Centrones (serotonin block): granisetron , ondasetron Alopecia Anthracyclines Taxanes Scalp-cooling techniques (not universally accepted) Cardiotoxicity Anthracyclines Cyclophosphamide 5-FU Early detection . Dexrazoxane
  • 18. CHEMOTHERAPY TOXICITIES ( II ) Pulmonary toxicity Bleom y c i n Alkylating s Gemcitabine Early detection . Corticosteroids Nephrotoxicity Platinum Methotrexate (↑dose) Adequate hydration Neurotoxicity Alkaloids Platinum Taxanes Early detection Gonadal d amage Alkylatings Others Sperm preservation Second m alignancies Alkylating s Avoid if possible responsible drugs and/or RT in curable diseases
  • 19. INTRODUCTION TO ENDOCRINE THERAPY (HORMONAL AGENTS)
  • 20.
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  • 29.  
  • 30.
  • 31.
  • 32.
  • 33.
  • 34. SMALL MOLECULES AND INTRACELLULAR SIGNAL TRANSDUCTION TYROSINE KINASE INHIBITORS
  • 35.
  • 36.
  • 37.
  • 38.
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  • 40.
  • 41.

Editor's Notes

  1. The original hypothesis for Iressa was that in a number of tumours EGFR expression was associated with a poor prognosis and that inhibition of the enzyme would have a number of effects that would impact on tumour growth. This hypothesis was supported by preclinical data.