1 / 52

In the Name of Allah the Most Beneficent and Merciful

In the Name of Allah the Most Beneficent and Merciful. CANCER CHEMOTHERAPY. BY Dr. NAEEM AHMED LAGHARI M.B.B.S., M.C.P.S., D.M.R.T., UICC fellow (London) ENEA fellow (Italy), Consultant Clinical Oncologist & Director. NUCLEAR INSTITUTE OF MEDICINE & RDIOTHERAPY (NIMRA),

raleigh
Télécharger la présentation

In the Name of Allah the Most Beneficent and Merciful

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. In the Name of Allah the Most Beneficent and Merciful

  2. CANCER CHEMOTHERAPY BY Dr. NAEEM AHMED LAGHARI M.B.B.S., M.C.P.S., D.M.R.T., UICC fellow (London) ENEA fellow (Italy), Consultant Clinical Oncologist & Director NUCLEAR INSTITUTE OF MEDICINE & RDIOTHERAPY (NIMRA), JAMSHRORO, PAKISTAN

  3. GENERAL MECHANISM The purpose of treating cancer with chemotherapeutic agents is to prevent cancer cells from multiplying, invading, metastasizing, and ultimately killing the Patient.

  4. BIOLOGICAL ASPECTS OF CANCER CHEMOTHERAPY MALIGNANT TRANSFORMATION Effective control of neoplastic cell growth by chemotherapy ideally will be based on knowledge of specific quantitative and qualitative changes in cellular biochemistry resulting from malignant transformation.

  5. BIOLOGICAL ASPECTS OF CANCER CHEMOTHERAPY MALIGNANT TRANSFORMATION Such transformation involves the occurrence of a heritable change in a stem cell of virtually any tissue, resulting in the production of daughter cells with absent or imperfect observation of normal homeostatic control or of normal differentiation.

  6. TUMOR CYTOKINETICS TUMOR CELL BURDEN The interval between the initial event causing malignant transformation and the appearance of a detectable tumor may vary from months to years, depending on the rate of cell division. The relationship between the number of doublings of the cancer cells and the presence of a clinically diagnosable tumor, usually requiring at least 109 cells in one site to produce a mass approximately 1cm in diameter.

  7. THE CELL CYCLE M The range of 1-5 days for both normal and tumor cells that are growing. G1 = 1.5 - 14 hours S = 6 – 9 hours G2 = 1 – 5 hours M = 0.5 – 1 hour G2 G0 G1 S (DNA SYNTHESIS)

  8. CELL CYCLE AND GROWTH FRACTION Each cell begins its growth during a postmitotic period, a phase called G1, during which enzymes necessary for DNA production, other proteins, and RNA are produced. G1 is followed by a period of DNA synthesis (S), in which essentially all DNA synthesis for a given cycle takes place.

  9. CELL CYCLE AND GROWTH FRACTION When DNA synthesis is complete, the cell enters a premitotic period (G2), during which further protein and RNA synthesis occurs. This gap is followed immediately be mitosis (M), at the end of which actual physical division takes place two daughter cells are formed, and each cell again enters G1. G1 phase is in equilibrium with a resting state called G0.

  10. TUMOR DOUBLING TIME The growth of a tumor is influenced by the heterogeneous nature of the population of cancer cells comprising its mass. A variable proportion of the cells are actively dividing at any one time, with human tumor growth fractions ranging from 90% for some lymphomas to under 10% for some adenocarcinomas.

  11. CELLULAR EFFECTS OF CHEMOTHERAPY The foregoing cytokinetic considerations have contributed to the concept that chemotherapy may be more effective against smaller, more actively growing tumor micrometastases, providing a rational basis for “reductive” surgical removal of all grossly apparent tumor masses followed by chemotherapy.

  12. PHARMACOLOGIC ASPECTS OF CANCER CHEMOTHERAPY 1. Drug absorption 2. Distribution 3. Biotransformation 4. Excretion

  13. 1. ABSORPTION a. Absorption of drugs determines the route of administration appropriate for a given agent, such as oral, intramuscular, intravenous, or intrathecal routes. b. The rate of absorption affects the duration and intensity of the exposure of cancer cells to the drug.

  14. 2. DISTRIBUTION The concentration and effectiveness of antineoplastic drugs can sometimes be enhanced by local or regional administration, including instillation into a body cavity such as the pleural space or intrathecal space, or into an artery with localization of the drug through perfusion of an extremity.

  15. 3. BIOTRANSFORMATION An example of biotransformation of a cancer chemotherapeutic agent is the activation of the alkylating agent cyclophosphamide by the mixed function oxidase system of the liver without which the agent is not effective.

  16. EXCERETION a. Excretion patterns of antieoplastic agents are important determinants of toxicity and of alterations in drug dosage, especially when there is impairment of excretory organ function. Since methotrexate, a dihydrofolate reductase inhibitor, is largely excreted by the kidney, doses must be reduced in the face or renal impairment.

  17. 4. EXCERETION b. In impaired liver function or biliary obstruction vincristine and doxorubicin doses should be reduced due to decreased excretion through bile.

  18. PRINCIPLES & PHARMACOLOGY OF CHEMOTHERAPY • Timing of chemotherapy • Induction chemotherapy. • Induction chemotherapy is the use of drugs as an initial therapy, for example in the treatment of acute leukemia to achieve significant cytoreduction (complete remission) of disease as initial therapy.

  19. B. Consolidation/Intensification chemotherapy. In consolidation /intensification treatment, given after remission, the same drugs used in induction (consolidation) or drugs that are non-cross resistant to the induction drugs (intensification) are repeated.

  20. C. Adjuvant chemotherapy. After eradication of disease with local treatment (surgical or radiation), adjuvant chemotherapy is used to treat putative microscopic disease and prevent local or distant relapse.

  21. D. Neoadjuvant chemotherapy. Before local therapy, neoadjuvant chemotherapy is given in hopes of reducing the extent of local treatment or increasing its effectiveness.

  22. E. Maintenance chemotherapy. Prolonged, low-dose outpatient chemotherapy is intended to prolong duration of remission and achieve cure in patients in remission.

  23. F. Salvage chemotherapy. After the failure of other treatments (surgery, radiation, or prior chemotherapy), salvage chemotherapy is used to control disease or provide palliation.

  24. II. Clinical end points in evaluating • response to chemotherapy • Complete response (CR) • Is the disappearance of disease on imaging studies for at least 1 month. In hematologic malignancies (e.g., in AML), a CR is defined as fewer than 5% blasts in the bone marrow (BM), no circulating blasts in the peripheral blood, and no extramedullary disease by day 14 after induction.

  25. 2. Partial Response (PR) Is the decrease of 50 % or more in the sum of the products of the biperpendicular diameters, with no new sites of disease for at least 1 month.

  26. 3. Stable disease In a patient with less than 50 % response without actual progression of disease.

  27. 4. Progression Is a 25 % increase in the sum of the products of the biperpendicular diameters of known lesions or any new sites of disease.

  28. CLASISIFICATION OF ANTI CANCER DRUGS • ALKYLATING AGENTS. • ANTIBIOTICS. • ANTI METABOLITIES. • PLANT DERIVED AGENTS. • HOROMONAL AGENTS. • BIOLOGICAL AGENTS.

  29. ALKYLATING AGENTS A biological and chemical activities of Nitrogen mustard were studied in period between World War-I and World War-II ( War Weapon ) to see effects of this drugs on skin, eyes and respiratory system.

  30. MECHANISM OF ACTION Alkylating agents are cell cycle phase non-specific agents. They exert their activity independent of the specific phase of cell cycle. Nitrogen mustard effects in GI and M phase.

  31. 1. BICHLOROETHEYLAMINES. Nitrogen mustard _________Mustine HCL. 6 mg/m^2 CycloPhosphamide________Endoxan 500 mg/m^2 Chlorambucil ___________ Leukeran 4-10 mg/m^2 Melphalan ______________ Alkeran 6 mg/ m^2 Igosphamide _____________ Holoxan 1-2 gm/m^2 2. NITROSOUREAS. Carmustine _____________ BCNU. 30-200 mg/m^2 Lomustine ______________ CCNU

  32. 3. NONLASSIC ALKYLATING AGENTS. Altertamine __________ 4-12 mgm/kg Dacarbazine ( DTIC) ____ 20mg/m^2 Procarbazine __________ Natulan 100 mg/m^2 4. PLATINUM COMPOUNDS . Cisplatin _______________ 50-100 mgm/m^2 Carboplatin _____________ 250 mgm/m^2 4. ALKYLALKONE SULFONATE. Busalphan _______________ Myleran 2-5 mgm/m^2

  33. 2. ANTIBIOTIC AGENTS:- MECHANISM OF ACTION:- These drugs act by binding to DNA and nicking one of its strands. During mitoses topoisomerase II level rise rapidly and the cell became more vulnerable to the effects of doxorubicin. 1. Doxorubicin ________________ 50-70 mgm/m^2 2. Dauorubicin _________________ 45 mg/m^2 3. Mitoxantrone ________________ 14 mg/m^2 4. Dactinomycin _______________ 0.5 mg /m^2 5. Bleomycin __________________ 10-15 mg/m^2 6. Mitomycin-C ________________ 6-10 mgm/m^2

  34. 3. ANTIMETABOLIC AGENTS This group of drugs interferes with metabolic process vital to physiology and proliferation of Cancer cells. Major classes of anti metabolites are antifolate, Purine analogous, pyrimidine analogous. 1. Antifolate Methotraxate 2. Purine analogous Thioguanine 3. Pyrimidine analogous 5-F.U.

  35. MECHANISM OF ACTION. All these drugs inhibit the synthesis of Purine or Pyrimidine nucleotides ( needed for DNA Synthesis ) or directly inhibit the enzymes of DNA and RNA Synthesis.

  36. COMMON ANTIMETABOLITES IN CLINICAL USE. • 1. 5-flouroucil ____________ 500-1000 mg/m^2 • 2. Methotrexade ___________ 30-40 mg /m^2 • 3. Thioguanine ____________ 100-200 mg/m^2 • 4. Hydroxurea _____________ 1 gm/m^2 • 5. 6- MercaptoPurine ________ 50 mgm/m^2 • 6. Cytosar _________________ 100 mgm/m^2

  37. 4. PLANT DERIVED AGENTS These agents used to treat cancer since 19th century. SOURCE Vincarosa (Vincristine, Vinblastine). Taxus brevofolia (Taxol) MECHANISM OF ACTION These agents do not target DNA but causes mitotic arrest of the cell in metaphase.

  38. PLANT DERIVED AGENTS. Vincristine ______________1.4 mgm/m^2 Vinblastine ______________ 5 mgm/m^2 Taxol___________________ 175-250 mgm/m^2 Etoposide _______________ 100 mgm/m^2

  39. 5. HORMONAL AGENTS Estrogen and progesterone are necessary to maintain the growth of breast and prostate tumors, by either reduction of the source of steroid or blockage of steroid action in the tumor itself.

  40. MALES High dose oestrogen (stillboestrol) or castration by removal of testis.An alternate approach to gonadectomy or oestrogen in men is the use of LHRH antagonist to desensitise the pituitary gland. LHRH Antagonist reduces the circulating androgens. Adrenal gland is a rich source of secreted androgen, which maintain prostate tumour growth.

  41. TAMAOXIFEN:- Antioestrogen used for treatement of breast cancer. This angent blocks oestrogen bindings to oestrogen receptors. DOSAGE:-10mg twice daily. MEGESTROL ACETATE:- Synthetic Steroid with Progestational and anti neoplastic activity used as a second line agent after tamoxifen for the treatment of advanced breast cancer and inoperable uterine tumours. DOSAGE:- 160mg/daily.

  42. TOXICITY OF ANTI CANCER DRUGS. 1. HAMATOLOGICAL Neutropeia, Thrombocytopenia, Anaemia, Bone marrow depression 2. SKIN Rashes, urticaria, alopecia. 3. G.I. TRACT Nausea, vomiting stomatits. diarhoea, muscositis, constipation..

  43. TOXICITY OF ANTI CANCER DRUGS. • 4.C.V.S • Arrhythmia, bradycardia, arterieoventricular, or bundle branch block. • NEUROLOGICAL • Neuropathy, Numbness, Parasthesia, muscle cramps, ataxia, foot and wrist drop, urinary retention, cranial nerve involvement leading to hoarseness of voice, diplopia, facial weakness, confusion, alteration in mental status.

More Related