chemotherapy

1. Chemotherapy Dr Gareth Noble (and Dr Sue Jordan) Lecture dedicated to Bridie Joyce (1952-2004)

3. Aims What is cancer? What are the treatment options? How do they work? What are the side effects? Patient management

4. What is cancer? Cancer is a whole-body disease, in which abnormal forms of the body's cells divide, multiply and spread, uncontrolled by normal regulators. Malignant neoplasms defined as: Uncontrolled proliferation Local invasiveness Metastasis Changes in some aspects of the original cell morphology/function

5. What are the treatment options? Treatments may be directed at: cure, palliation or prolonging life. Chemotherapy: inhibit rate of growth or kill cancerous cells Not specific – need to target the accelerated cell division that distinguishes cancer cells from normal cells

6. Drugs prescribed to treat cancer include: Cytotoxics – main focus of the lecture Immunological therapies: immunosuppressants, such as corticosteroids; monoclonal antibodies, rituximab, alemtuzumab; interferon alfa Hormones and hormone antagonists: important in treatment of breast, uterine and prostate malignancies. E.g. anti-oestrogen treatments, such as tamoxifen, anastrozole

7. Cytotoxic drugs damage actively dividing cells. However, they are unable to destroy any malignant cells which are ‘resting’. If these become active later, the immune system often cannot eliminate them.

8. Cell Cycle Overview

9. THE CELL CYCLE

10. Therefore, anti-cancer therapy may be repeated in cycles, to catch any malignant cells as they emerge from their 'resting' state. However, patients who experience severe adverse drug reactions in early cycles, may decline further treatments.

11. PULSE THERAPY

12. EFFECTS of TREATMENT

13. Cytotoxic drugs are usually divided into: Alkylating drugs e.g. cyclophosphamide, chlorambucil Cytotoxic antibiotics e.g. doxorubicin, bleomycin Mitotic inhibitors: Vinca alkaloids (e.g. vincristine) and etoposide Antimetabolites e.g. methotrexate, cytarabine, cladribine Other anti-neoplastic drugs, including: platinum compounds; taxanes.

14. Alkylating agents (eg Melphalan) MoA: creates robust bonds between strands of DNA preventing replications and breakages Administrations: oral or intravenously Indications: myeloma’s and some solid tunours, used frequently in Rx of Leukaemia’s, lympthoma’s, and ovarian cancers Adverse effects: cytotoxicity

15. Cytotoxic Antibodies (Dactinomycin) MoA: prevents transcription and DNA replication (ie DNA synthesis) Admin: Intravenous Indications: mainly used for paediatric cancers Adverse: cytotoxicity, does-dependent cardiotoxicity (free radial damage)

16. Mitotic inhibitors (Vincristine) MoA: prevents mitosis and division of cells Admin: IV or orally depending on the agent Indications: acute leukaemias, lymphomas, some solid tumours Adverse: an indiscriminate agent, affects all cells (normal and cancerous); cytotoxicity; neurological disturbance (neuropathy, loss of reflexes)

17. Antimetabolites (Methotrexate) MoA: inhibits DNA synthesis Admin: Orally, IV, intramuscularly & intrathecally. Indications: acute lymphoblastic leukaemia, non-Hogkins lympthoma, skin cancer Adverse: Cytotoxicity

18. Anti-cancer drugs may be prescribed alone or together with surgery or radiotherapy. Cytotoxic drugs are often prescribed in combinations to enhance effectiveness and prevent drug resistance.

19. Administration of anti-cancer drugs is guided by local and national protocols (BNF no.49, Dougherty & Lister 2004). Patients should be fully informed of potential benefits and side-effects. Tablets should never be crushed, and capsules never opened. Preparation and administration of intravenous drugs must be under carefully controlled conditions.

20. Guidelines on handling cytotoxic drugs: Trained personnel should reconstitute cytotoxics; Reconstitution should be carried out in designated areas; Protective clothing (including gloves) should be worn; The eyes should be protected and means of first aid should be specified; Pregnant staff should not handle cytotoxics; Adequate care should be taken in the disposal of waste material, including syringes, containers and absorbent material.

21. Doses are calculated by specialists in relation to the patient’s condition, therapeutic regimen, age, liver and kidney function, weight and (sometimes) height or body surface area. Recording weight and height on drug charts facilitates surface area calculations.

22. Adverse effects of cytotoxic drugs Malignant cells are similar to normal cells. Therefore, cytotoxics also kill dividing cells in healthy tissue, causing severe side-effects. Some drugs also cause organ damage.

23. CELL DIVISION

24. Common problems include:

25. Gastro-intestinal disturbance

33. Low platelet count, causing bruising and bleeding.

35. Skin damage

37.

40. Organ damage

45. Cautions and contra-indications Impaired liver or kidney function may necessitate dose reduction. Dehydration (from vomiting, diarrhoea, hypercalcaemia) may necessitate postponement of treatment.

46. Pregnancy Pregnant staff (and those who may be pregnant) should not handle cytotoxics. Patients should be advised to use effective barrier contraception, if appropriate. Many anti-cancer drugs can damage the fetus or cause miscarriage. If cancer is diagnosed during pregnancy, the woman is confronted with very difficult decisions.

47. Breastfeeding is contra-indicated. Children Growth should be monitored and optimum nutrition encouraged. If physical isolation is necessary to reduce exposure to infection, discuss measures to minimise social isolation.

48. Older patients are more vulnerable to adverse effects, as they have reduced bone marrow, cardiac and renal reserves. Immunisations may be ineffective. If live vaccines, such as BCG, are administered, vaccine-related illness may develop. Disposal of patients' body fluids/ secretions should follow local protocols.

49. Interactions Patients should seek advice before taking any non-prescription drugs, e.g. cimetidine, aspirin and alcohol. Many non-steroidal anti-inflammatory drugs can worsen the side-effects of methotrexate. Effectiveness of etoposide may be reduced by St.John’s Wort.

50. Anticancer drugs interact with many other drugs. For example, co-administration with other drugs which adversely affect bone marrow, such as clozapine, may increase the risk of neutropenia.

51. A MODEL FOR IMMUNITY MALNUTRITION INFECTIONS protein fungi bacterial STRESS protozoal DRUGS im. Sup. TUMOUR Cytotoxics steroids REACTIVATION INFECTIONS TB acute viral shingles chronic bacterial chronic protozoal MALIGNANCY CHRONIC DISEASE e.g. RF, diabetes

53. Patient Management Issues Need Pt assessment: General condition Individual response to agents Adverse reactions (inc hypersensitivity) Use developed guidelines (Protection) Review periodic laboratory assessments (ie blood counts, liver function, bone marrow) Pt and family education!

54. References Websites: http://www.cancer.org/docroot/ETO/eto_1_3_Chemotherapy_Principles.asp (American Cancer Society) http://www.hse.gov.uk/press/2003/e03179.htm (Safe Handling Regs) http://www.patient.co.uk/showdoc/27000559/ (Patient UK) http://www.cancerhelp.org.uk/ (Cancer Research UK) Textbooks: Applied pharmacology : an introduction to pathophysiology and drug management for nurses and healthcare professionals / Sylvia Prosser ... [et al.] Call Number:RM301 >APP Basic pharmacology for nurses / Bruce D. Clayton, Yvonne N. Stock. Location:Morriston Library Call Number:QV4 >BAS Pharmacology / Humphrey P. Rang ... [et al.] Call Number:RM300 >RAN5