Chemotherapy for Nurses and Medical Students

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Information about Chemotherapy for Nurses and Medical Students

Published on December 16, 2016

Author: DrShadSalimAkhterAkh

Source: slideshare.net

1. Cancer Treatment Local• Surgery • Radiotherapy • Chemotherap y • Laser

2. Cancer Treatment Systemic• Chemotherapy • Hormone therapy • Biological response modifiers • Gene therapy

3. Chemotherapy Mechanism of Action Macromolecular synthesis & function Cytoplasmic organisation Cell membrane synthesis function

4. M G2 S GIB Daughter Cell Irreversibly Differentiated Cell GO Prolonged G1 G1A Amount of DNA Tetraploid Di- ploid DNA Synthesis

5. G (resting)0 16 - 20 S DNA synth 18 - 30 G1 RNA and protein synthesis Phase Function Duration (hrs) 2-10 RNA & PS 0.5-1 M Mitosis G 2 Differentiation or continued replication Cell cycle - Kinetics

6. D N A RNA Protein Tubulin Salv pathwayDe novo synth Purines dTMP dCMP FH4 FH2 CMP dUMP Transcription Free rad dam Strand breaks Alkylation Intercalation Translation Replication Bleomycin Etoposide Teniposide Dactinomycin Adriamycin Daunomycin Adriamycin DaunomycinAra-C 5FU 5FU Vincristine Vinblastine Taxol 6-MP 6-TG Mechlor Cyclo Ifosf Melpha Carbop Cispla Nitro Proca Dacar Methotrexate L-Asparaginase

7. Chemotherapy- TypesPhase specific G2 Phase Etoposide Bleomycin Taxol M Phase Vincristine Vinblastine Vindesine G0 Phase G1 Phase L-Asparg Steroids S Phase Antimetab Hydroxyurea Cell cycle specific

8. Chemotherapy Types Cycle specific Cycle non specific Phase non specific Phase non specific Steroids Alkyl. agents Procarbazine Dacarbazine Streptozotocin Alkylating agents Dactinomycin Anthracyclines 5-Fluorouracil

9. 10 12 1010 108 10 6 104 102 NumberofCells Doublings 1mg 1 g Days 40 80 120 160 22 22 4020 3010 1g 1 kg

10. 10 10 10 10 10 10 12 10 8 4 2 2 3 54 6Begin (Clinical Complete Response) < 10 Cells9 (Complete Tumor Eradication) < 1 Cell Time TumorSize (CellNumber) Cycles 6 All cells sensitive Drug accessibility uniform No change in cell sensitivity. Assumption

11. Necrotic Fraction Non Proliferative (Avascular) Fraction Proliferative Fraction Differentiated Fraction Fraction G0Exfoliation Metastases

12. CytotoxicEffect Plasma Drug Concentration Therapeutic Index Normal Tissue Response Tumor Response 100 50

13. Chemotherapy Combinations-- Why? • Prevention of resistant clones • Cytotoxicity to resting and dividing cells • Biochemical enhancement of effect • Rescue

14. Chemotherapy Indications To cure certain malignancies To palliate symptoms Treat aggressive cancer in asymptomatic patients Adjuvant therapy

15. Chemotherapy Contraindications Lack of facilities to monitor response and side effects Expected survival shorter than required for reponse Asymptomatic pt with slow growing incurable tumor Expected survival shorter than required for benefit of

16. Chemotherap y Responsiveness NHLymphoma Burkitt's Diff Large cell Foll mix lymp Rhabdomyosar Testicular ca Ac. Lymp Leuk Ac. Myel Leuk Ewing's Sarc GTND Hodgkin's dis Wilm's tumor Curable Tumors

17. Chemotherap y Responsiveness Hairy cell leuk H & Neck ca SCCL Multiple myel NHL Foll. lymph Ovarian ca Anal Ca Bladder ca Breast ca Cervix ca CLL CML Endomet ca Significant Activity

18. Chemotherap y Responsiveness Melanoma Pancreat ca Prostatic ca RCC Soft tis sar Astrocyto Colorect ca Hepatoma Kaposi's sar NSCCL Minimal Activity

19. Chemotherapy Adjuvant Therapy Breast carcinoma Colorectal carcinoma Osteogenic sarcoma Ovarian carcinoma Testicular carcinoma

20. Chemotherap yAdministration Preparation Laminar flow Aseptic technique Personal care Compatibility Storage Concentration Route of administration

21. Chemotherap yAdministration Vein selection Large forearm veins Dorsum of hand Exercises Avoid Antecubital fossa Wrist Covering the cannula tip

22. New Therapeutic Modalities •Immunotherapy –Vaccines –Cell transfer therapy •Targeted therapy –Receptor bases therapy •Anti-angiogenesis therapy

23. Cancer Vaccines •Lymphoma •Gastro intestinal cancer •Prostate cancer •Melanoma

24. Rosenberg SA NEJM 2004; 350:1461 Lymphocytes: Sufficient number of recognizing tumor cells Reach the tumor Must be able to destroy the tumor cells

25. Rescue hybridoma

26. TARGETTEDTARGETTED THERAPYTHERAPY

27. Targeted Therapy •MOA against cell surface markers – Lymphoma cells (like anti CD20) •Receptor based therapy – Estrogen receptors – Tyrosine kinases – RAR – EGF – VEGF •Proteasome inhibitors

28. Estrogen biosynthesis Tumor cell Nucleus Inhibition of Estrogen Dependent Growth Inhibition of cell proliferation Estrogen biosynthesis AntiestrogensAntiestrogens Aromatase inhibitors Aromatase inhibitors

29. Chromosomal Abnormality 90-95% pts have this translocation

30. Krause DS et al: N Engl J Med 2005; 353:172

31. Cell surface HER2 protein (HER2 receptor) Other EGFR/HER family receptor Cell nucleus

32. Activated HER2-HER2 dimers Growth signal Cell nucleus

33. Tumor cell growth

34. Herceptin monoclonal antibody

35. Chemotherap y Ideal Agent • Lethal Action on cancer cells • No effect on host cells

36. Single DosesSingle Doses MedianGrowthDelay 20 15 10 5 0 300250150500 60 40 20 0 PercentToxicDeaths Cyclophosphamide (mg/kg) (days)

37. LIVER KIDNEY EXCRETED EXCRETED LYMPHATICS EXTRACELLULAR COMPARTMENTS COMPARTMENTS (N or T) BILE INTRACELLULAR BLOOD CELLS GUT I/V --> PLASMA

38. CytotoxicEffect Plasma Drug Concentration Therapeutic Index Normal Tissue Response Tumor Response 100 50

39. Chemotherapy Side effects Bone marrow DrugOrgan effected Leucopenia Thrombocytopenia Anaemia Amost all except steroids Bleo, L asparg G I T Stomatitis Diarrhea Paralytic ileus Adria, bleo,meth 5 FU, Act D Meth, 5FU Vincristine

40. Chemotherapy Side effects Skin DrugOrgan effected Hyperpigmentat Alopecia Bleo, bus, 5FU Adria, cyclo, Act D CNS Per Neuropathy Deafness Vincristine Vinblastine Cisplatin

41. Chemotherapy Side effects Heart DrugOrgan effected Heart failure (late) Adria, dauno epirub, 5FU Lung Fibrosis (late) Bleomycin busulfan, metho, cyclo Bladder Cystitis Cyclo, ifos

42. Chemotherapy Side effects Kidney DrugOrgan effected Abnormal Renal function Cisplatin, mtx, mithra Liver Abnormal Liver function Methotrexate L-aspar, mithra

43. Chemotherapy Side effects Late ChronicImmediate & Early Bone marrow Cardiac toxicity Pulmonary toxicity 2nd malignancies Sterility Psychological Local vascular damage Local pain Nausea Vomiting

44. Chemotherapy Monitoring Therapy Extent of disease Toxicity of therapy Previous chemotherapy Previous radiotherapy Timing of toxicity Flow sheets... Lab investigations

45. Chemotherap yDose Modification Infection Active drug toxicity Radiotherapy Organ dysfunction Myelosuppression

46. Chemotherap yDrug resistance Reduce tumor bulk Use drug combinations Coldman Goldie hypo Schedule therapy to prevent phase escape Cell kinetics & resistance

47. Chemotherapy Drug resistance Biochemical drug resistance Increased efflux Decreased influx Increased catabolism Bypass lethal blockade

48. Chemotherapy Drug resistance Multiple drug resistance Increased activity of p-glycoprotien Abnormal topoisomerase activity Mutation of MDR genes

49. Dose intensity and Response Ridgway Osteogenic Sarcoma Study Skipper HE: 1986 Cy l-PAM Average %CR %Cure 0.38 0.82 0.60 100.0 60.0 0.75 0.18 0.47 100.0 40.0 0.25 0.55 0.44 100.0 10.0 0.50 0.12 0.31 10.0 0.0 0.17 0.36 0.27 0.0 0.0

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