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Anti Cancer New Program
 

Anti Cancer New Program

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    Anti Cancer New Program Anti Cancer New Program Presentation Transcript

    • ANTI ~ CANCER DRUGS Zenaida N. Maglaya, MD, FPSECP
    • CANCER
      • is a disease in which there in uncontrolled multiplication & spread within the body of abnormal forms of the body’s own cells.
    • Special Characteristics of Cancer Cells
      • Uncontrolled Proliferation
      • Dedifferentiation and loss of function
      • Invasiveness
      • Metastasis
    • Management of Cancer
      • Surgical
      • Irradiation
      • Chemotherapy
    • PHASES OF CELL CYCLE
    • Mitosis M Synthetic S Pre-Synthetic G 1 Post –Synthetic G 2 DIFFEREN-TIATION G 0
    • Cell Cycle Non – Specific (CCNS) Agents
      • ALKYLATING
      • AGENTS
      • Busulfan
      • Carmustine
      • Cyclophosphamide
      • Lomustine
      • Mechlorethamine
      • Melphalan
      • Thiothepa
      • ANTHRACYCLINES
      • Daunorubicin
      • Doxorubicin
      • Epirubicin
      • Idarubicin
      • Mitoxantrone
      • ANTI TUMOR
      • ANTIBIOTICS
      • Dactinomycin
      • Mitomycin
      • CAMPTOTHECINS
      • Irinotecan
      • Topotecan
      • PLATINUM ANALOGS
      • Carboplatin
      • Cisplatin
      • Oxaliplatin
    • Cell Cycle Specific (CCS) Agents
      • ANTIMETABOLITES
      • Capecitabine
      • Cladribine
      • Cytarabine
      • Fluorouracil
      • Gemcitabine
      • Mercaptopurine
      • Methotrexate
      • Thioguanine
      • ANTITUMOR ANTIBIOTIC
      • Bleomycin
      • EPIPODOPHYLLO-
      • TOXINS
      • Etoposide
      • Teniposide
      • TAXANES
      • Docetaxel
      • Paclitaxel
      • VINCA ALKALOIDS
      • Vinblastine
      • Vincristine
      • Vinorelbine
      • CCS:
      • Hematological malignancies,
      • solid tumors in growth fraction
      • CCNS:
      • low groth fraction solid tumors
      • high growth fraction tumors
    • CANCER CHEMOTHERAPEUTIC AGENTS
      • C. CYTOTOXIC ANTIBIOTICS
      • microbial in origin
      • prevent cell division
      • D. PLANT DERIVATIVES
      • affect microtubules and formation of mitotic spindle
    •  
    •  
    • CANCER CHEMOTHERAPEUTIC AGENTS
      • II. HORMONES
      • suppress hormone secretion
      • antagonize hormone action
      • III. MISCELLANEOUS AGENTS
    • CLASSIFICATION OF ANTI-CANCER DRUGS
    • POLYFUNCTIONAL ALKYLATING AGENTS
      • A. NITROGEN MUSTARD
      • 1. CYCLOPHOPHAMIDE
      • 2. CHLORAMBUCIL
      • 3. MECHLORETHAMINE
      • 4. IFOSFAMIDE
      • 5. MELPHALAN
      • 6. ESTRAMUSTINE
      • B. NITROSOUREA
      • CARMUSTINE(BNCU)
      • 2. SEMUSTINE (methyl CCNU)
      • 3.LOMUSTINE( CCNU)
      • 4.STREPTOZOCIN
    • POLYFUNCTIONAL ALKYLATING AGENTS
      • C.ALKYL SULFONATE
      • 1. BUSULFAN
      • D.AZIRIDINE
      • 1. THIOTEPA
      • E. TREOSULPHAN
    • RELATED DRUGS PROBABLY ACTING AS ALKYLATING AGENTS
      • PROCARBAZINE
      • CISPLATIN
      • DACARBAZINE
      • CARBOPLATIN
      • ALTRETAMINE
    • ANTIMETABOLITES
      • A. FOLATE ANTAGONIST
      • 1. METHOTREXATE
      • B. PURINE ANTAGONIST
      • 1. MERCAPTOPURINE 4. FLUDARABINE
      • 2. THIOGUANINE 5. PENTOSTATIN
      • 3. CLADRIBINE
      • C. PYRIMIDINE ANTAGONIST
      • 1. FLUOROURACIL 3. CYTARABINE
      • 2. CAPECITABINE 4. GEMCITABINE
    • PLANT ALKALOIDS
      • 1. VINBLASTINE
      • 2. VINCRISTINE
      • 3. VINORELBINE
      • 4. PODOPHYLLOTOXINS (ETOPOSIDE & TENIPOSIDE)
      • 5. CAMPTOTHECINS (TOPOTECAN & IRINOTECAN)
      • 6. TAXANES (PACLITAXEL & DOCETAXEL)
    • ANTIBIOTICS
      • 1. ANTHRACYCLINES(DOXORUBICIN & DAUNORUBICIN)
      • 2. DACTINOMYCIN(ACTINOMYCIN D)
      • 3. PLICAMYCIN(METHRAMYCIN
      • 4. MITOMYCIN (MITOMYCIN C)
      • 5. BLEOMYCIN
      • 6. EPIRUBICIN
      • 7. MITOZANTRONE
    • HORMONAL AGENTS
      • A. ADRENOCORTICOIDS
      • 1. PREDNISONE
      • 2. HYDROCORTISONE
      • B. ANDROGENS
      • 1. TESTOSTERONE
      • 2.FLUOXYMESTERONE
      • C. ESTROGENS
      • 1. DIETHYLSTILBESTROL
      • 2. ETHINYL ESTRADIOL
      • D. PROGESTINS
      • 1. HYDROXYPROGESTERONE
      • 2.MEDROXYPROGESTERONE
    • HORMONAL AGENTS
      • E. ESTROGEN INHIBITOR :
      • 1. TAMOXIFEN
      • 2. TORIMIFENE
      • F. ANDROGEN INHIBITOR
      • 1. FLUTAMIDE
      • 2.CYPROTERONE
    • HORMONAL AGENTS
      • G. GONADOTROPIC RELEASING HORMONE AGONIST
      • (GnRH)
      • 1. LEUPROLIDE
      • 2. GOSERELIN
      • 3. NAFERELIN
      • H. AROMATASE INHIBITORS
      • 1. AMINOGLUTETHIMIDE & TRILOSTANE
      • 2. ANASTROZOLE
      • 3. LETROZOLE
      • 4.EXEMESTANE
    • MISCELLANEOUS ANTI - CANCER DRUGS
      • 1. IMATINIB
      • 2. GROWTH FACATOR RECEPTOR INHIBITOR
      • A. CEFUXIMAB
      • B. GEFITINIB & ERLOTINIB
      • C. BEVACIZUMAB
      • 3. ASPARAGINASE (CRISANTASPASE)
      • 4. HYDROXYUREA
      • 5. RETINOIC ACID DERIVATIVE (TRETINOIN)
      • 6. ARSENIC TRIOXIDE
    • MISCELLANEOUS ANTI - CANCER DRUGS
      • 6. BONE MARROW GROWTH FACTORS
      • GRANULOCYTE COLONY-STIMULATING FACTOR
      • (G-CSF, FILGRASTIM)
      • GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR (GM-CSF, SARGAMOSTIM)
      • AMI FOSTINE (ETHYOL)
    • MISCELLANEOUS ANTI - CANCER DRUGS
      • MONOCLONAL ANTIBODIES
      • 1. RIFUXIMAB
      • 2. TRASTUZUMAB
      • RADIOACTIVE ISOTOPES
      • RADIOACTIVE IODINE-TREATMENT OF THYROID CA
      • BIOLOGICAL RESPONSE MODIFIER
      • * INTERFERONS, ALDESLEUKIN, TRETINOIN
    • ALKYLATING AGENTS
      • ALKYLATING AGENTS
      • I. PHARMACOKINETICS
        • oral or parenteral administration
        • hepatic microsome P450 mediated cyclophosphamide ACROLEIN…….MESNA
        • nitrosoureas: highly lipid soluble
        • unchanged form in urine (cisplatin)
        • terminated via hepatic metabolism: procarbazine
      • II. PHARMACODYNAMICS OF ALKYLATING AGENTS
      • CCNS: Form reactive molecules…> alkylation (N7 guanine)………>
      • Cross linking of bases
      • abnormal base pairing &
      • DNA strand breakage
      • RESISTANCE THRU:
      • ↑ DNA repair / ↓ drug permeability
      • production of trapping agents
      • ALKYLATING AGENTS
      • III. CLINICAL INDICATIONS
      • A. CYCLOPHOSPHAMIDE:
      • non Hodgskin’s lymphoma, breast & ovarian CA, neuroblastoma
      • B. MECHLORETHAMINE: Hodgskin ‘s disease (MOPP)
      • C. CARMUSTINE & LOMUSTINE: brain tumors
      • D. BUSULFAN: chronic myelogenous leukemia / Thiotep a: ovarian ca
      • IV. ADVERSE EFFECTS OF ALKYLATING AGENTS
      • NAUSEA & VOMITING Myelosuppression
      • hemorrhagic cystitis (cyclophosphamide)
      • peripheral neuropathy (altretamine))
      • adrenal insufficiency, pulmonary fibrosis & skin pigmentation (busulfan)
    • RELATED DRUGS PROBABLY ACTING AS ALKYLATING AGENTS
      • PROCARBAZINE
      • in Hodgkin’s lymphoma
      • leukemogenic, teratogenic, mutagenic
      • N & V, myelosuppression, hemolytic anemia, pulmonary reaction, disulfiram like effect, skin rashes, CNS depression
      • B.CISPLATIN:
        • inorganic metal complex
        • In testicular CA, bladder, lung & ovarian CA
        • Nausea, vomiting, myelosuppression
        • Nephrotoxicity, neurotoxocity, ototoxicity, anaphylaxis
    • ANTIMETABOLITES
      • .METHOTREXATE
      • PHARMACODYNAMICS
      • Inhibits dihydrofolate reductase…………..>
      • INTERFERES w/ thymidylate & purine nucleotide , serine, methionine
      • … > DNA synthesis & cell division block
      • RESISTANCE:
      • 1. ↓ drug accumulation
      • 2.change in drug sensitivity or activity of dihydrofolate reductase
      • 3. ↓ for mation of polyglutamates
    • METHOTREXATE
      • PHARMACOKINETICS: Oral, IV. IM, intrathecal
      • CLINICAL USE: choriocarcinoma, acute leukemias, nonHodgskins and cutaneous T cell lymphomas, breast CA; rheumatoid arthritis, psoriasis & abortifacient
      • ADVERSE EFFECTS; N & V & D, mucositis
      • myelosuppression ; skin effects
      • reduced by folinic acid (leukoverin rescue)
      • enhance by salicylates, NSAID, sulfonamides, sulfonylureas
    • MERCAPTOPURINE (6 MP) & THIOGUANINE (6 TG)
      • 6 THIOINOSINIC ACID….activated by hypoxanthine - guanine phosphoribosyltransferase (HGPRT)….>
      • inhibit enzymes involved in purine metabolism
      • RESISTANCE:
      • decrease HGPRT activity
      • increase alkaline phosphatases that inactivate the toxic nucleotides
    • MERCAPTOPURINE (6 MP) & THIOGUANINE (6 TG)
      • PHARMACOKINETCS: oral; urine
      • 6MP metabolism inhibited by allopurinol
      • CLINICAL INDICATIONS
      • acute leukemias ; chronic myelocytic leukemias
      • ADVERSE EFFECTS:
      • myelosuppression, immunosuppression, hepatotoxicity
    • FLUOROURACIL ( 5FU)
      • Uracil, interferes with DTMP
      • ( 5 FDUMP)………..> thymidylate synthase….> “thymineless death” 5FdUTP….> DNA synthesis inhibition
      • RESISTANCE:
        • decreased activation of 5 FU
        • increased thymidylate synthase activity
        • reduce drug sensitivity of this enzyme
    • FLUOROURACIL ( 5FU)
      • PHARMACOKINETICS : IV
      • widely distributed; hepatic metabolism
      • CLINICAL USES: colorectal, stomach, pancreas, esophagus, liver, bladder, breast, head and neck, liver & ovarian cancers
      • topical: keratoses & basal cell cancer
      • ADVERSE EFFECTS : myelosuppression, GIT effects & alopecia, hand & foot syndrome, neurotoxicity
    • CYTARABINE (ARA-C)
      • activated to Ara CTP (inhibitor of DNA polymerase)
      • most S specific
      • RESISTANCE
      • ↓ uptake / ↓ conversion to Ara CTP
      • CLINICAL USE : acute leukemias
      • ADVERSE EFFECTS : myelosuppression & GIT irritation; neurotoxicity & peripheral neuritis
    • PLANT DERIVATIVES
      • A. VINBLASTINE & VINCRISTINE
      • * Periwinkle plant
        • spindle poisons
        • prevent assembly of tubulin dimmers into microtubules
        • block formation of mitotic spindle
        • act on M phase
        • RESISTANCE: increase efflux of the drug
      • PHARMACOKINETICS
      • Parenterally
      • Hepatic metabolism
    • A. VINBLASTINE & VINCRISTINE
      • CLINICAL USE
      • VINCRISTINE: MOPP & COP; acute leukemias, lymphomas, wilm’s tumor, choriocarcinoma
      • VINBLASTINE: ABVD; other lymphomas, neuroblastoma, testicular cancer, Kaposi’s sarcoma
      • VINORELBINE: advance non- small cell cancer
      • ADVERSE EFFECTS:
      • VINBLASTINE: GIT distress, alopecia, bone marrow suppression, alopecia
      • VINCRISTINE: neurotoxicity, areflexia, peripheral neuritis, paralytic ileus
    • B. ETOPOSIDE & TENIPOSIDE
      • Podophyllotoxins from May apple root
      • interacts w/ topoisomerase II….>inhibits mitochondrial electron transport….> increase degradation of DNA
      • late S and early G2 phase
      • oral; elimination thru the kidneys
      • small cell lung CA, prostate & testicular CA
      • cause bone marrow suppression, GIT effects, alopecia
    • C. TOPOTECAN & IRINOTECAN
          • from Comptotheca acuminate tree
          • inhibit topoisomerase I
          • DNA damage
          • Topotecan: advanced ovarian cancer, small cell lung cancer
          • Irinotecan: ,metastatic colorectal CA
          • Cause: myelosuppression & diarrhea
    • D. PACLITAXEL & DOCETAXEL
        • Taxanes from Western yew
        • Prevent microtubule disassembly into tubulin monomers; by IV
        • Advanced breast and ovarian cancers
        • Paclitaxel : N & V, myelosuppression, peripheral neuropathy, hypersensitivity rx
        • Docetaxil : neurotoxicity & bone marrow suppression, fluid retention, rash
    • ANTIBIOTICS
    • A. DOXORUBICIN & DAUNORUBICIN
        • intercalate between base pairs………> inhibit topoisomerase II….>
        • generate free radicals …………> block synthesis of RNA & DNA…>
        • DNA strand scisision
        • Given IV; excreted in the bile & urine
    • A. DOXORUBICIN & DAUNORUBICIN
        • DAUNORUBICIN: acute leukemias
        • DOXORUBICIN: ABVD; myelomas, sarcomas, breast, endometrial, lungs, ovarian & thyroid cancers
        • CARDIOTOXICITY ( USE DEXRAZOXANE, radical scavenger)
        • Bone marrow suppression, GIT effects, alopecia
    • B. BLEOMYCIN
        • DNA strand breakage …..……>
        • inhibit DNA synthesis
        • CCS on G2 phase
        • USE: testicular cancer & Hodgskin’s lymphoma, lymphomas, squamous cell cancer
        • Hypersensitivity reaction, pulmonary dysfunction
    • C. DACTINOMYCIN
      • binds to double-stranded DNA & inhibits DNA dependent RNA synthesis
      • USE: melanoma & wilm’s tumor
      • Causes bone marrow suppression, skin & GIT irritation
    • D. MITOMYCIN
      • Activated to form an alkylating agent…> cross links DNA
      • IV given; hepatic metabolism
      • USE: adenocarcinoma of the cervix, stomach, pancreas & lungs
      • Causes myelosuppression
    • HORMONAL AGENTS
    • HORMONAL ANTICANCER AGENTS
      • A. GLUCOCORTICOIDS
      • Prednisone/ Hydrocortisone:
      • acute & chronic lymphocytic leukemias, hodgskin’s disease, other lymphomas
      • Fluid retention, hypertension, diabetes, Increase susceptibility to infection
    • HORMONAL ANTICANCER AGENTS
      • B. SEX HORMONES
        • estrogen, progestins, androgens: hormone dependent cancers to change the hormone balance
        • Fluoxymesterone: advanced breast CA
        • Diethylstilbestrol: prostatic cancer
    • HORMONAL ANTICANCER AGENTS
      • C. SEX HORMONES ANTAGONISTS
        • tamoxifen: estrogen receptor partial agonist
        • may cause nausea & vomiting, hot flushes, vaginal bleeding, hypercalcemia, ocular, dysfunction& peripheral edema
        • Flutamide: prostatic cancer
        • Cause:gynecomastia, hot flushes, hepatic dysfunction
    • HORMONAL ANTICANCER AGENTS
      • D. GONADOTROPIN-RELEASING HORMONE ANALOGS (GnRh ANALOG)
        • Leuprolide, Goserelin & nafarellin
        • inhibit release of pituitary LH & FSH
        • prostatic cancer
        • may cause: bone pain, gynecomastia, hematuria, impotence & testicular atrophy
    • HORMONAL ANTICANCER AGENTS
      • E. AROMATASE INHIBITORS
        • anastrozole & leterozole
        • inhibit enzyme that catalyzes the conversion of androstenedione to estrone
        • advanced breast cancer
        • diarrhea, nausea, hot flushes, bone & back pain, peripheral edema
          • MISCELLANEOUS ANTICANCER AGENTS
    • MISCELLANEOUS ANTICANCER AGENTS
      • A. Asparaginase
        • depletes serum asparagines
        • used in leukemias & lymphomas
        • given IV
        • Cause severe hypersensitivity reactions, neurotoxicity & bleeding
    • MISCELLANEOUS ANTICANCER AGENTS
      • B. IMATINIB
      • Inhibitor of the tyrosine kinase domain of the Bcr- Abl oncogenes & prevent the phosphorylation of the kinase substrate by ATP
      • For CML, GIT stromal tumors
      • N /V/D, Fluid Retention, Myalgia
    • GROWTH FACTOR RECEPTOR INHIBITORS
      • A. CEFUZIMAB
      • Colorectal Ca
      • B. GEFITINIB & ERLOTINIB
      • NSCLCa
      • C. BEVACIZUMAB
      • Metastatic colororectal Ca
    • MISCELLANEOUS ANTICANCER AGENTS
      • C. Interferons
        • endogenous glycoproteins with antineoplastic, immunosuppresion & antiviral actions
        • Use in hairy cell leukemias, chronic myelogenous leukemia, T cell lymphomas
        • Cause myelosuppression & neurologic dysfunction
    • MISCELLANEOUS ANTICANCER AGENTS
      • D. Monoclonal Antibodies
        • RIFUXIMAB
        • Monoclonal antibody to a surface protein non- Hodgskin’s lymphoma cells
        • TRASTUZUMAB: monoclonal antibody to a surface protein in breast cancers that over express the HER2 protein
        • Toxicity: hypersensitivity reactions & myelosuppression
        • Cardiac dysfunction with trastuzumab
    • STRATEGIES IN CANCER CHEMOTHERAPY
      • I. Each drug should be active when used alone against the particular cancer
      • II. The drug should have different mechanism of action
      • III. Cross resistant between drugs should be minimal.
      • IV. The drugs should have different toxic effects.
    • SAMPLES OF COMBINATION CHEMOTHERAPY
      • . HODGKIN’S DISEASE: MOPP / ABVD
      • 2. NON-HODGKIN’S LYMPHOMA: COP
      • 3. TESTICULAR CARCINOMA: PVB
      • 4. BREAST CANCER: CMF/CAF
    • CANCER CHEMOTHERAPY ACRONYMS
      • ABVD : Doxorubicin (adriamycin),
      • bleomycin, vinblastine, dacarbazine
      • CHOP :Cyclophosphamide, doxorubicin
      • (hydroxydaunorubicin), vincristine
      • (oncovin), Prednisone
      • MOPP : Melchlorethamine, vincristine
      • (oncovin), Procarbazine, Prednisone
    • ACRONYMS
      • COP :Cyclophosphamide, vincristine (oncovin), prednisone
      • PEB: Platinuml(cisplatin),
      • etoposide bleomycin
      • CMF : Cyclophosphamide, methotrexate, Fluouracil
      • CAF: cyclophosphamide, adriamycin(doxorubicin) , 5 FU
    • THE LEUKEMIAS
    • 1. ACUTE LEUKEMIA
      • ALL: induction: vincristine & prednisone
      • >remission maintenance: mercaptopurine, methotrexate / cyclophosphamide
      • AML: cytarabine, mitoxantrone or daunorubicin or idarubicin
    • 2.CHRONIC LEUKEMIA
      • CML: Imatinib, busulfan, or interferon
      • bone marrow transplant
      • CLL: chlorambucil & prednisone
      • fludarabine
    • THE LYMPHOMAS
      • 1. HODGKIN’S DISEASE
        • MOPP
        • ABVD
      • 2. NON-HODGKIN’S LYMPHOMA
        • CHOP
      • MULTIPLE MYELOMA
      • melphalan & prednisone
    • CARCINOMA OF THE BREAST
      • Stage I SURGERY
      • Stage II: positive lymph nodes: SURGERY plus cytotoxic chemo in 6 cycles at one month apart; CMF/CAF; tamoxifen in postmenopausal women
      • Trastazumab: HER-2/neu receptors
      • Stage III & IV Palliative
      • aminoglutethimide, trastuzumab
    • CARCINOMA
      • WILM’S TUMOR : vincristine plus dactinomycin after surgery & radiotherapy
      • NEUROBLASTOMA : doxorubicin + cyclophosphamide + vincrisitne
      • CARCINOMA OF THE PANCREAS : gemcitarabine
      • POLYCYTHEMIA VERA : busulfan, chlorambucil or cyclophosphamide
    • CARCINOMA
      • CHORIOCARCINOMA OF THE UTERUS :
        • Methotrexate / Etoposide & Cisplatin
      • CARCINOMA OF THE OVARY : cisplatin & paclitaxel
      • TESTICULAR NEOPLASMS : PEB
      • CARCINOMA OF THE PROSTATE
        • Estrogen, leuprolide & Flutamide
      • CARCINOMA OF THE THYROID
        • Radioiodine, doxorubicin & cisplatin
    • CARCINOMA
      • GASTROINTESTINAL CARCINOMAS
      • Stomach: 5FU plus cisplatin
      • Colon: 5 FU + leucoverin + oxiplatin
      • MALIGNANT MELANOMA & MISC SARCOMAS:
        • dacarbazine & cisplain
      • BRAIN TUMORS
      • > carmustine, multimodality therapy
    • LUNG CARCINOMA
      • Small cell( SCLCa)
      • Non-small cell(NSCLCa)75-80%
      • CISPLATIN & TAXANES
      • Others: methotrexate, vincristine, vinblastine, doxorubicin, mitomycin C
    • THANK YOU VERY MUCH !!! Cast your burden on the Lord. And He shall sustain you He shall never permit the Righteous to be moved. Psalm 55 : 22