Principles of chemotherapy ppt

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  • Docetaxel, in doses ranging from 50–70 mg/m2, was administered for 1 h by drip
    infusion either just before or after a 5-min bolus i.v. injection of doxorubicin at dosages from 40–50 mg/m2. The sequence of drug administration was switched after the first course in each
    patient, and the sequence of drug administration thereafter depended on the patient’s choice. Twenty-five patients were initially assessable for toxicity. The MTD in the sequence of
    doxorubicin after docetaxel was 40 and 50 mg/m2, respectively, with the dose-limiting toxicity of neutropenia. On the other hand, the MTD of the sequence of docetaxel after doxorubicin
    was 70 and 50 mg/m2, respectively. The dose-limiting toxicities in this sequence were neutropenia and diarrhea. Duration of grade 4 neutropenia in the sequence of docetaxel followed by doxorubicin was significantly longer than
    that in the alternate sequence (P = 0.0062). However, there was no difference in pharmacokinetic parameters of docetaxel, doxorubicin, and doxorubicinol between the two sequences. The sequence of 50 mg/m2 doxorubicin
    followed by 60 mg/m2 docetaxel is recommended for subsequent clinical trials for practical reasons.
  • 10. Principles of Chemotherapy: Side Effects of Chemotherapy
    There are multiple side effects of chemotherapy. Some are common, such as alopecia, neutropenia. Some are rare such as cardiotoxicity. The side effects are generally the consequence of the cytotoxic effect of chemotherapy on normal cells, however they can also be related to the direct toxicity of the drug.
  • 24% of all colon cancers are right sided and will be missed by a flex sig.
  • Thom George
  • Thom George
  • Principles of chemotherapy ppt

    1. 1. PRINCIPLES OF CHEMOTHERAPY Dr. R. RAJKUMAR M.D; D.M.Dr. R. RAJKUMAR M.D; D.M. ASSISTANT PROF.& CONSULTANTASSISTANT PROF.& CONSULTANT MEDICAL ONCOLOGISTMEDICAL ONCOLOGIST
    2. 2. ETIOLOGY OF CANCER CarcinogenesisCarcinogenesis  A cancer, is thought to developA cancer, is thought to develop from a cell in which the normalfrom a cell in which the normal mechanisms for control ofmechanisms for control of growth and proliferation aregrowth and proliferation are altered.altered.  Current evidence supports theCurrent evidence supports the concept of carcinogenesis as aconcept of carcinogenesis as a multistage process that ismultistage process that is genetically regulatedgenetically regulated
    3. 3. ETIOLOGY OF CANCER Genetic and Molecular Basis of CancerGenetic and Molecular Basis of Cancer  Two major classes of genes are involved inTwo major classes of genes are involved in carcinogenesis: oncogenes and tumorcarcinogenesis: oncogenes and tumor suppressor genessuppressor genes
    4. 4. Invasivity Motility Aneuploidy Angiogenesis Imune Defense Evasion Deregulated Proliferation Altered Energy Metabolism Immortalization (Anti-Apoptosis) HallmarksHallmarks oof Cancerf Cancer Target Areas for Therapeutic InterventionsTarget Areas for Therapeutic Interventions
    5. 5. MODALITIES OF TREATMENT  1-local therapy:1-local therapy:  -surgery.-surgery.  -radiation therapy.-radiation therapy.  2-systemic treatment:2-systemic treatment:  chemotherapy.chemotherapy.  Hormonal therapyHormonal therapy..  Monoclonal antibodies.Monoclonal antibodies.  Radioactive material.Radioactive material.  3-supportive care.3-supportive care.  4-non-conventional therapy4-non-conventional therapy..
    6. 6. SURGERY  Surgery was the first modality usedSurgery was the first modality used successfully in the treatment ofsuccessfully in the treatment of cancer.cancer.  It is the only curative therapy for someIt is the only curative therapy for some common solid tumors.common solid tumors.  The most important determinant of aThe most important determinant of a successful surgical therapy are thesuccessful surgical therapy are the absence of distant metastases and noabsence of distant metastases and no local infiltrationlocal infiltration..
    7. 7. Cont:  Microscopic invasion of surroundingMicroscopic invasion of surrounding normal tissue will necessitatenormal tissue will necessitate multiple frozen section.multiple frozen section.  Resection or sampling of regionalResection or sampling of regional lymph node is usually indicated.lymph node is usually indicated.  Surgery may be used for palliation inSurgery may be used for palliation in patients for whom cure is notpatients for whom cure is not possible.possible.  Has significant role in cancerHas significant role in cancer preventionprevention..  E.gE.g familial polyposis coli.familial polyposis coli.
    8. 8. RADIATION THERAPY
    9. 9. RADIATION THERAPY  Radiation therapy: is a local modalityRadiation therapy: is a local modality used in the treatment of cancer .used in the treatment of cancer .  Success depend in the difference inSuccess depend in the difference in the sensitivity between the tumor andthe sensitivity between the tumor and normal tissue.normal tissue.  It involves the administration ofIt involves the administration of ionizing radiation in the form of x-rayionizing radiation in the form of x-ray or gamma rays to the tumor site.or gamma rays to the tumor site.  Method of delivery: ExternalMethod of delivery: External beam(teletherapy). Internal beambeam(teletherapy). Internal beam therapy(Brachytherapytherapy(Brachytherapy).).
    10. 10. Cont:  Radiation therapy is planned andRadiation therapy is planned and performed by a team of nurses,performed by a team of nurses, dosimetrists,physician and radiationdosimetrists,physician and radiation oncologist.oncologist.  A course of radiation therapy isA course of radiation therapy is preceded by a simulation session inpreceded by a simulation session in which low-energy beam are used towhich low-energy beam are used to produce radiograghic images thatproduce radiograghic images that indicate the exact beam locationindicate the exact beam location..
    11. 11. Cont:  Radiation therapy is usually deliveredRadiation therapy is usually delivered in fractionated doses such as 180 toin fractionated doses such as 180 to 300 cGy per day,five times a week for300 cGy per day,five times a week for a total course of 5-8 weeks.a total course of 5-8 weeks.  Radiation therapy with curative intentRadiation therapy with curative intent is the main treatment in limited stageis the main treatment in limited stage Hodgkin’s disease , some NHL,Hodgkin’s disease , some NHL, limited stage CA prostate, gynecologiclimited stage CA prostate, gynecologic tumors & CNS tumortumors & CNS tumor ..  Also can be used in palliative &Also can be used in palliative & emergency setting.emergency setting.
    12. 12. COMPLICATION OF RADIATION  There are two types of toxicities - acute andThere are two types of toxicities - acute and long term toxicity.long term toxicity.  Systemic symptoms such as Fatigue , localSystemic symptoms such as Fatigue , local skin reaction , GI toxicity , oropharyngealskin reaction , GI toxicity , oropharyngeal mucositis , xerostomia & myelosuppression.mucositis , xerostomia & myelosuppression.  Long-term sequelae: may occur manyLong-term sequelae: may occur many months or years after radiation therapy.months or years after radiation therapy.  Radiation therapy is known to be mutagenic,Radiation therapy is known to be mutagenic, carcinogenic ,and teratogenic ,and havingcarcinogenic ,and teratogenic ,and having increased risk of developing both secondaryincreased risk of developing both secondary leukemia and solid tumorleukemia and solid tumor..
    13. 13. NUCLEAR MEDICINE
    14. 14. RADIONUCLIDES  For decades have been usedFor decades have been used systemically to treat malignantsystemically to treat malignant disorders.disorders.  They are administer by specialists inThey are administer by specialists in nuclear medicine or radiationnuclear medicine or radiation oncologist.oncologist.  Radioactive iodine in the from ofRadioactive iodine in the from of 131131 I isI is effective therapy for welleffective therapy for well differentiated thyroid cadifferentiated thyroid ca  Strontium-89. Is used for theStrontium-89. Is used for the treatment of bony metastasis .It is antreatment of bony metastasis .It is an alkaline earth element in the samealkaline earth element in the same family as calciumfamily as calcium
    15. 15. CHEMOTHERAPY
    16. 16. Paul Ehrlich 1854 - 1915 • Father of Chemotherapy • Salvarsan for Treatment of Syphilis • Nobel Prize 1908 • “Magic Bullet Concept”
    17. 17. HISTORICAL PERSPECTIVE  Nitrogen mustards were a product ofNitrogen mustards were a product of the secret war gas programs in boththe secret war gas programs in both world warsworld wars  In WWII, an explosion at Bar HarborIn WWII, an explosion at Bar Harbor exposed seamen to mustard gas - theyexposed seamen to mustard gas - they developed severe marrow anddeveloped severe marrow and lymphoid hypoplasialymphoid hypoplasia  Led to the useLed to the use of theseof these agents toagents to treat Hodgkins and non-Hodgkinstreat Hodgkins and non-Hodgkins lymphomas at Yale in 1943lymphomas at Yale in 1943
    18. 18. HISTORICAL PERSPECTIVE  In the 1950’s, folic acid wasIn the 1950’s, folic acid was shown to accelerate theshown to accelerate the progression of childhoodprogression of childhood leukemias; led to development ofleukemias; led to development of folic acid antagonistsfolic acid antagonists  In the 1960’s, combinationIn the 1960’s, combination chemotherapy for childhoodchemotherapy for childhood leukemias and Hodgkinsleukemias and Hodgkins lymphoma began to be usedlymphoma began to be used
    19. 19. CHEMOTHERAPY  Systemic chemotherapy is the mainSystemic chemotherapy is the main treatment available for disseminatedtreatment available for disseminated malignant diseases.malignant diseases.  Progress in chemotherapy resulted inProgress in chemotherapy resulted in cure for several tumors.cure for several tumors.  Chemotherapy usually require multipleChemotherapy usually require multiple cycles.cycles.
    20. 20. MODES OF CHEMOTHERAPY  PRIMARY CHEMOTHERAPYPRIMARY CHEMOTHERAPY - chemotherapy- chemotherapy is used as the sole anti-cancer treatment inis used as the sole anti-cancer treatment in a highly sensitive tumor typesa highly sensitive tumor types  Example – CHOP for Non-HodgkinsExample – CHOP for Non-Hodgkins lymphomalymphoma  ADJUVANT CHEMOTHERAPYADJUVANT CHEMOTHERAPY – treatment is– treatment is given after surgery to “mop up” microscopicgiven after surgery to “mop up” microscopic residual diseaseresidual disease  Example – Adriamycin, cyclophosphamideExample – Adriamycin, cyclophosphamide for breast cancerfor breast cancer  NEOADJUVANT CHEMOTHERAPYNEOADJUVANT CHEMOTHERAPY –– treatment is given before surgery to shrinktreatment is given before surgery to shrink tumor and increase chance of successfultumor and increase chance of successful resectionresection  Example – Adriamycin, ifosfamide forExample – Adriamycin, ifosfamide for osteosarcomaosteosarcoma
    21. 21. MODES OF CHEMOTHERAPY  CONCURRENT CHEMOTHERAPYCONCURRENT CHEMOTHERAPY –– treatment is given simultaneous totreatment is given simultaneous to radiation to increase sensitivity ofradiation to increase sensitivity of cancer cells to radiationcancer cells to radiation  Example – Cisplatin, 5-fluourouracil,Example – Cisplatin, 5-fluourouracil, XRT for head and neck tumorsXRT for head and neck tumors
    22. 22. There is a wide variation in sensitivity of various cancers to chemotherapy HighHigh IntermediateIntermediate LowLow LymphomaLymphoma BreastBreast Head and neckHead and neck LeukemiaLeukemia ColonColon ProstateProstate Small Cell LungSmall Cell Lung cancercancer Non-small cell lungNon-small cell lung cancercancer GastricGastric Testicular cancerTesticular cancer PancreaticPancreatic
    23. 23. CANCER CHEMOTHERAPY: PRINCIPLES 1. The “Silver Bullet” isn’t out there1. The “Silver Bullet” isn’t out there.. 2.2. Conventional chemotherapy targetsConventional chemotherapy targets have been the cell cycle, microtubuleshave been the cell cycle, microtubules and DNAand DNA 3. Combination chemotherapy improves3. Combination chemotherapy improves responses over single agent, but doseresponses over single agent, but dose intensity must be maintained.intensity must be maintained.
    24. 24. CANCER CHEMOTHERAPY: PRINCIPLES 44.. It is better to treatIt is better to treat micrometastatic diseasemicrometastatic disease 5. Phase I trials define an5. Phase I trials define an MTD --a Maximum ToleratedMTD --a Maximum Tolerated Dose - this may not equateDose - this may not equate to the Maximum Therapeuticto the Maximum Therapeutic
    25. 25. CANCER CHEMOTHERAPY: PRINCIPLES 6.6. For classical chemotherapy to beFor classical chemotherapy to be effective, cell proliferation iseffective, cell proliferation is required. Indolent (slowlyrequired. Indolent (slowly growing) cancers are typicallygrowing) cancers are typically resistant. If therapy isresistant. If therapy is ineffective, tumor indolenceineffective, tumor indolence determines survival.determines survival. 7.Almost7.Almost all who die with cancerall who die with cancer have been treated withhave been treated with chemotherapychemotherapy ---- thus drugthus drug resistance is a major cause ofresistance is a major cause of
    26. 26. GOMPERTZIAN GROWTH Growth rates are exponential atGrowth rates are exponential at early stagesearly stages of development andof development and slowerslower at later stages ofat later stages of developmentdevelopment Biological growth follows this characteristicBiological growth follows this characteristic curve.curve.
    27. 27. GOMPERTZIAN GROWTH MODEL Initial tumour growth is first order, with later growth being much slower Smaller tumour grows slowly but large % of cell dividing Medium size tumour grows more quickly but with smaller growth fraction Large tumour has small growth rate and growth fraction
    28. 28. AIM OF COMBINATION CHEMOTHERAPY INCREASED EFFICACYINCREASED EFFICACY Different mechanisms of action Compatible side effects Different mechanisms of resistance ACTIVITYACTIVITY SAFETYSAFETY
    29. 29. PRINCIPLES OF CHEMOTHERAPY Rationale for combinationRationale for combination chemotherapychemotherapy  Different drugs exert their effectDifferent drugs exert their effect through different mechanismsthrough different mechanisms and at different stages of the celland at different stages of the cell cycle, thus maximize cell killcycle, thus maximize cell kill  Decease the chance of drugDecease the chance of drug resistanceresistance
    30. 30. Combination chemotherapy: Metastatic Breast Cancer Agents Dose Intensity PR (%)* CR (%)* Cyclophosphamide 1 1 35 0 Methotrexate 1 1 25 0 Fluorouracil 1 1 25 0 Doxorubicin (A) 1 1 50 5 CMF 0.5+0.33+0.33 1.17 50 5 CAF 0.5+0.7+0.33 1.53 75 10 * Patients with overt metastases and no prior chemotherapy except in the adjuvant setting PR = partial response CR = complete response (“Cancer Medicine”, Holland and Frey (eds.), 5th Ed., 2002)
    31. 31. CANCER CHEMOTHERAPY: PRINCIPLES More is better, to a point! A B V D FFP: 81% M O P P/ A B V FFP: 67% A B V D FFP: 65% M O P P FFP: 63% S I N G L E A G E N T FFP: 20% Advanced Hodgkin’s Disease
    32. 32. Careful Sequencing is Critical Docetaxel Doxorubicin Doc Dox 40 mg/m2 50 mg/m2 Dox Doc 50 mg/m2 70 mg/m2 Itoh et al. Study of Sequence Switching of Administration Clin. Cancer Res 6:4082-4090, 2000
    33. 33. CANCER CHEMOTHERAPY: Adjuvant Chemotherapy Improves Survival Osteosarcoma: Sarcoma of the bone 1970’s: Surgery if no evidence of metastatic disease One-half developed metastatic disease, Usually within 6 mos of surgery 20% 5 year survival. Thus:80% had micrometastatic disease. With adjuvant chemotherapy: 60-70% long-term survival
    34. 34. CANCER CHEMOTHERAPY: adjuvant chemotherapy improves survival Breast Cancer C CMF ∆ Odds 1970’s: 3 yr RFS 1 -3 Nodes+ 64% 78% 39% >3 Nodes+ 44% 49% 9% CAF vs. CMF: 2% - 12% improvement reported Widely adopted: Adriamycin + Cytoxan Increasingly, followed by Taxol
    35. 35. Interphase Prophase Metaphase Anaphase Interphase Cytokinesis STAGES OF MITOSIS:
    36. 36. Cancer Chemotherapy  After completion of mitosis, the resulting daughterAfter completion of mitosis, the resulting daughter cells have two options:cells have two options:  (1) they can either enter G1 & repeat the cycle or(1) they can either enter G1 & repeat the cycle or  (2) they can go into G0 and not participate in the cell(2) they can go into G0 and not participate in the cell cycle.cycle.  Growth fraction - at any particular time some cellsGrowth fraction - at any particular time some cells are going through the cell cycle whereas other cellsare going through the cell cycle whereas other cells are resting.are resting.  The ratio of proliferating cells to cells in G0, isThe ratio of proliferating cells to cells in G0, is called the growth fraction.called the growth fraction.  A tissue with aA tissue with a large percentage of proliferatinglarge percentage of proliferating cellscells & few cells in& few cells in G0G0 has ahas a high growth fraction.high growth fraction.  Conversely, a tissue composed ofConversely, a tissue composed of mostly of cells inmostly of cells in G0G0 has ahas a low growth fractionlow growth fraction..
    37. 37. MECHANISMS OF CHEMOTHERAPY  Damage the DNADamage the DNA of the affected cancerof the affected cancer cells. It is not always possible to be selective, butcells. It is not always possible to be selective, but selectivity is the ultimate goal of any drug.selectivity is the ultimate goal of any drug. e.g.e.g.,, cisplatin (Platinol®), daunorubicin (Cerubidine®),cisplatin (Platinol®), daunorubicin (Cerubidine®), doxorubicin (Adriamycin®), and etoposidedoxorubicin (Adriamycin®), and etoposide (VePesid®).(VePesid®).  Inhibit the synthesis of new DNAInhibit the synthesis of new DNA strands to stop the cell from replicating, becausestrands to stop the cell from replicating, because the replication of the cell is what allows the tumorthe replication of the cell is what allows the tumor to grow.to grow. e.ge.g..,, methotrexate (Abitrexate®),methotrexate (Abitrexate®), mercaptopurine (Purinethol®), fluorouracilmercaptopurine (Purinethol®), fluorouracil (Adrucil®), and hydroxyurea (Hydrea®).(Adrucil®), and hydroxyurea (Hydrea®).  Stop the mitotic processesStop the mitotic processes of a cell.of a cell. Stopping mitosis stops cell division (replication) ofStopping mitosis stops cell division (replication) of the cancer and may ultimately halt the progressionthe cancer and may ultimately halt the progression of the cancer.of the cancer. e.g.e.g., Vinblastine (Velban®),, Vinblastine (Velban®), Vincristine (Oncovin®)Vincristine (Oncovin®) and Pacitaxel (Taxol®).and Pacitaxel (Taxol®).
    38. 38. CLASSIFICATION OF CYTOTOXIC DRUG  Cytotoxic agent can be roughlyCytotoxic agent can be roughly categorized based on theircategorized based on their activity in relation to the cellactivity in relation to the cell cycle.cycle. p h a s e n o n s p e c ific . p h a s e s p e c ific c y to to x ic d r u g
    39. 39. Cont :  What is the difference between phaseWhat is the difference between phase specific & phase non specific?…..specific & phase non specific?…..  Phase non-specific:Phase non-specific:  The drugs generally have a linearThe drugs generally have a linear dose-response curve(dose-response curve(↑↑ the drugthe drug administration ,theadministration ,the ↑↑ the fraction ofthe fraction of cell killed).cell killed).  Phase specific:Phase specific:  Above a certain dosage level,furtherAbove a certain dosage level,further increase in drug doesn’t result inincrease in drug doesn’t result in more cell killing.but you can playmore cell killing.but you can play with duration of infusion.with duration of infusion.
    40. 40. Two Broad Classes of Chemotherapy Drugs:  Cytotoxic agentsCytotoxic agents  Cisplatin – causes DNA damageCisplatin – causes DNA damage  5-Fluourouracil – blocks enzymes5-Fluourouracil – blocks enzymes necessary for RNA and DNA synthesisnecessary for RNA and DNA synthesis  Docetaxel – inhibits microtubuleDocetaxel – inhibits microtubule formationformation  Targeted therapiesTargeted therapies  Erlotinib – small molecule inhibitor theErlotinib – small molecule inhibitor the EGFR tyrosine kinaseEGFR tyrosine kinase  Cetuximab – antibody that binds to EGFRCetuximab – antibody that binds to EGFR
    41. 41. CHEMOTHERAPEUTIC AGENTS  Alkylating agents:Alkylating agents:  Antimetabolites:Antimetabolites:  Antitumor antibiotic:Antitumor antibiotic:  Plant alkaloidsPlant alkaloids::  Other agentsOther agents  Hormonal agent:Hormonal agent:  Immunotherapy:Immunotherapy:
    42. 42. Chemotherapy – routes of administration  oraloral  intravenousintravenous  intramuscularintramuscular  intrathecalintrathecal  intraperitonealintraperitoneal  intrapleuralintrapleural ►isolated organisolated organ perfusionperfusion ►intrapericardialintrapericardial  portal veinportal vein  LimbLimb intraarterialintraarterial
    43. 43. PLANNING DRUG DOSES AND SCHEDULES  DosesDoses - based on body surface area- based on body surface area - differ between children and adults- differ between children and adults - adjusted for people who are elderly, have poor- adjusted for people who are elderly, have poor nutritional status, have already taken or takingnutritional status, have already taken or taking other medications, have already received orother medications, have already received or are currently receiving radiation therapy, have loware currently receiving radiation therapy, have low blood cell counts, or have liver or kidney diseasesblood cell counts, or have liver or kidney diseases
    44. 44. PLANNING DRUG DOSES AND SCHEDULES  Schedule (Cycles)Schedule (Cycles) - A cycle = one dose followed by several- A cycle = one dose followed by several days or weeks without treatment for normaldays or weeks without treatment for normal tissues to recover from the drug’s side effectstissues to recover from the drug’s side effects The number of cycles = based on the type andThe number of cycles = based on the type and stage of cancer, and side effectsstage of cancer, and side effects
    45. 45. HEMATOLOGICAL CONSIDERATIONS FOR DOSE SCHEDULING  LifespanLifespan  Platelet - 7-10 daysPlatelet - 7-10 days  Red blood cell - 120 daysRed blood cell - 120 days  Neutrophils - 6-12 hoursNeutrophils - 6-12 hours  Time from Stem Cell to Mature NeutrophilTime from Stem Cell to Mature Neutrophil  ~7-10 days~7-10 days
    46. 46. DECIDING ON TREATMENT INTERVALS  As short as possibleAs short as possible  Recovery of bone marrowRecovery of bone marrow  Supplies mature cells for 8-10 daysSupplies mature cells for 8-10 days  Onset 9-10th daysOnset 9-10th days  Lowest (nadir) 14-18Lowest (nadir) 14-18thth daysdays  Recovery by day 21-28.Recovery by day 21-28.  Usual schedule is q21-28 days.Usual schedule is q21-28 days.
    47. 47. COMPLICATION OF CHEMOTHERAPY  Every chemotherapeutic will have someEvery chemotherapeutic will have some deleterious side effect on normal tissue .deleterious side effect on normal tissue .  E.G; Myelosuppression,nausea&vomiting,E.G; Myelosuppression,nausea&vomiting, Stomatitis,and alopecia are the mostStomatitis,and alopecia are the most frequently observed side effects.frequently observed side effects.
    48. 48. MucositisMucositis Nausea/vomitingNausea/vomiting DiarrheaDiarrhea CystitisCystitis SterilitySterility MyalgiaMyalgia NeuropathyNeuropathy Alopecia Pulmonary fibrosis Cardiotoxicity Local reaction Renal failure Myelosuppression Phlebitis SIDE EFFECTS OF CHEMOTHERAPYSIDE EFFECTS OF CHEMOTHERAPY
    49. 49. CRITERIA USED TO DESCRIBE RESPONSE ARE:  Complete response (complete remission)is(complete remission)is the disappearance of all detectablethe disappearance of all detectable malignant disease.malignant disease.  Partial response : is decrease by more than: is decrease by more than 50% in the sum of the products of the50% in the sum of the products of the perpendicular diameters of all measurableperpendicular diameters of all measurable lesions.lesions.  Stable disease : no increase in size of any: no increase in size of any lesion nor the appearance of any newlesion nor the appearance of any new lesionslesions..  Progressive disease : means an increase by: means an increase by at least 25% in the sum of the products ofat least 25% in the sum of the products of the perpendicular diameters of measurablethe perpendicular diameters of measurable lesion or the appearance of newlesion or the appearance of new lesions.lesions.
    50. 50. Methods to increase the efficacy of chemotherapy  standard dosingstandard dosing  high dosehigh dose  dose-densedose-dense
    51. 51. ENDOCRINE THERAPY
    52. 52. ENDOCRINE THERAPY  Many hormonal antitumor agents are functional agonist orMany hormonal antitumor agents are functional agonist or antagonist of the steroid hormone family.antagonist of the steroid hormone family.  Adrenocorticoids:Adrenocorticoids:  Antiandrogen:Antiandrogen:  Estrogen:Estrogen:  Antiestrogen:Antiestrogen:  ProgestinsProgestins  Aromatase inhibitor:Aromatase inhibitor:  Gonadotropin-releasing hormone agonists:Gonadotropin-releasing hormone agonists:  Somatostatin analogues:Somatostatin analogues:
    53. 53. ADRENOCORTICOSTEROID  Are frequently used in combination regimen forAre frequently used in combination regimen for the treatment of lymphocytic leukemia andthe treatment of lymphocytic leukemia and lymphoma.lymphoma.  They function by binding to glucocorticoid-They function by binding to glucocorticoid- specific receptors present in lymphoid cells andspecific receptors present in lymphoid cells and initiate programmed cell deathinitiate programmed cell death  They most commonly used agent areThey most commonly used agent are prednisone,methylprednisone,dexamethosone.prednisone,methylprednisone,dexamethosone.
    54. 54. ANTIANDROGENS  Flutamide :Flutamide : Effectively blocks the binding of androgen toEffectively blocks the binding of androgen to its receptor in the periphral tissue .its receptor in the periphral tissue . It is used in the treatment of disseminatedIt is used in the treatment of disseminated prostate caprostate ca
    55. 55. BIOLOGIC THERAPY  Immunotherapy:Immunotherapy:  CytokinesCytokines  Cellular therapy.Cellular therapy.  Tumor vaccine:Tumor vaccine:  Hematopoietic growth factors.Hematopoietic growth factors.
    56. 56. Definition New technology and drugs that allow the cancer treatment to “target” a certain cancer cell by interfering with the natural functions of tumor growth How they work They “target” specific parts of a cancer cell or its actions; hand in a glove analogy What it means in cancer treatment  Potentially fewer side effects “TARGETED” THERAPIES
    57. 57. Targeted Therapies
    58. 58. SIGNALLING PATHWAYS
    59. 59. TARGETED THERAPIES  Monoclonal antibodiesMonoclonal antibodies: proteins that trigger the: proteins that trigger the body’s pathways involved in cancer growth tobody’s pathways involved in cancer growth to fight cancer more effectively.fight cancer more effectively.  EGFREGFR: family of receptors found on surface of: family of receptors found on surface of normal and cancer cells that bind with annormal and cancer cells that bind with an epidermal growth factor (EGF) causing cells toepidermal growth factor (EGF) causing cells to divide.divide.  Tyrosine Kinase InhibitorsTyrosine Kinase Inhibitors: Part of the cell that: Part of the cell that signals it to divide and multiply; enhances cellsignals it to divide and multiply; enhances cell growth. Still investigationalgrowth. Still investigational
    60. 60. TK TKATP ATP CellCell ProliferationProliferation AntiapoptosiAntiapoptosi ss AngiogenesisAngiogenesis Gene Transcription Cell Cycle Progression + MetastasesMetastasesSurvivalSurvival Tumor Cell StimulationTumor Cell Stimulation
    61. 61. TK TK TK Strategies to Inhibit Signaling -- -- -- tyrosinetyrosine kinasekinase inhibitorsinhibitors ““-ibs”-ibs” Anti- mAbsAnti- mAbs ““-mab”-mab” Anti-ligandAnti-ligand mAbsmAbs ““-mab”-mab” ATP
    62. 62. CONCLUSIONS  People with cancer are living longerPeople with cancer are living longer  The focus is on quality of life in addition toThe focus is on quality of life in addition to quantityquantity  People surviving cancer want to live normal livesPeople surviving cancer want to live normal lives  New treatments of various kinds are available andNew treatments of various kinds are available and there is no need to sufferthere is no need to suffer

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