Cancer Therapeutics Lecture 1 PDF

Pharmacy Cancer Therapeutics Dr Sarah Needs 1 Copyright University of Reading Outline Lecture 1 (Today) Diagnosis Modes of treatment for cancer Lecture 2 Mechanism of action for common chemotherapy drugs Common side effects for patients...

Pharmacy Cancer Therapeutics Dr Sarah Needs 1 Copyright University of Reading Outline Lecture 1 (Today) Diagnosis Modes of treatment for cancer Lecture 2 Mechanism of action for common chemotherapy drugs Common side effects for patients Lecture 3 Radiotherapy and nuclear pharmacy 2 Please be aware that discussions or references to cancer may evoke strong emotions or memories, and it’s important to approach these topics with sensitivity and understanding. 3 You should be able to….. Briefly discuss the role of the pharmacist in diagnosis of cancer Explain the aims and strategy of cancer treatment Explain the modes of therapy available and their common uses Explain the rationale behind the use to chemotherapy Compare and contrast the use of combination chemotherapy and single agent therapy, including the use of new targeted therapy Explain the key aspects of a chemotherapy regimen. 4 Diagnosis of Cancer Cancer is a broad term. Over 200 different types of cancer Each type of cancer can be diagnosed and treated differently (which makes it very difficult) 5 Signs of cancer (from the NHS website) Non-specific Specific symptoms symptoms Heartburn (often organ specific) Weight loss Lots of Blood in the urine Itchy skin general (bladder) symptoms Cough that lasts more Fatigue which could Tummy pain be linked to than 3 weeks (lung) other Physical lump in specific Moles healthcare area Bleeding problems Bloating Coughing 6 Key diagnostic factors Symptoms are wide, sometimes non-specific (fatigue) and varied Therefore, diagnosis would be via specialist teams. Common test that help with diagnosis include: Imaging such as CT and PET scans Laboratory test (in vitro diagnostic: IVD) looking for tumour biomarkers Biopsy Physical exam 7 Diagnosis of Cancer Cancer is a broad term. Solid tumours or blood cancers – require very different diagnosis A physical exam to detect a lump won’t be appropriate for leukaemia 8 Pharmacist’s role: Diagnosis Medication management Patient Education Collaboration with wider healthcare team 9 Pharmacist’s role in diagnostics If many symptoms are non-specific, how can you effectively refer to a GP? Red flag symptoms that would require further investigation by GP. Extensive list, often organ specific. Non-specific symptoms include: Unexplained weight loss Unexplained bleeding New unexplained lumps not normal for the patient Unexplained and persistent or recurrent infections Non-specific symptoms with specific duration or age 10 Pharmacist’s role in diagnostics Red flag symptoms – Extensive list, specific guidance, often organ specific Some organ specific examples include: Bladder – Blood in urine Bowel – persistent and unexplained abdominal pain Lung – cough which lasts for more than 3 weeks Many symptoms shared with other health issues. Therefore, need to be sensitive when communicating with patient. 11 Table 1: Red flag symptoms necessitating referral Source: suspected cancer guidelines based on the Quick Reference Guide for Pharmacists 2017 All ages: Unexplained lump in neck; Unexplained ulceration in mouth lasting more than three weeks; Head and neck Age 45 years and over with: Persistent hoarseness for four weeks; Repeat purchase of throat lozenges or medicine. 12 Patient’s journey Earlier diagnosis and treatment linked to better patient outcomes: (Delayed treatment often increased complications and increased care costs) NHS Faster Diagnosis Standard Diagnosis or cancer ruled out within 28 days of referral by GP Treatment to begin within 62 days of referral Aim to ensure patient start treatment as soon as possible and to put their minds to rest more quickly if no cancer diagnosis. 13 Patient’s journey Specific pathway to cover Non-specific symptoms only: Historically seen by GP several times and eventually present with more advanced stage cancer Diagnostic pathways to better triage these patients: blood tests, symptom specific tests – CT, endoscopy. 14 Management : Aims and strategy The priorities in dealing with cancer are:- 1. Prevention – Reducing risk factors and vaccination programmes HPV vaccine (50% of viruses are cancer risks – nearly everyone has had HPV) Cancer Vaccine Launchpad (CVLP) – accelerated development of personalised cancer vaccines treatment 2. Early Detection – Public health awareness and cancer screening programmes, use of diagnostics. Bowel Breast Cervical 3. Cure - Total eradication of cancer cells in the patient. 15 Cancer Treatment When therapy is initiated, there must be a realistic assessment of the cancer management programme. Hierarchy of aims in cancer management:- 1. Cure - eradication of tumour and metastasis. 2. Remission/mitigation - significant reduction in tumour load. Increased survival. 3. Symptomatic / palliation - treatment of secondary complications. Relief of symptoms (any stages of treatment) 4. Terminal care - improve quality of life. Optimize symptom control. 16  CURING CANCER Survival varies between cancers Difference in 5-year survival rate often due to stage of cancer at diagnosis. Nearly have of all cancers were diagnosed at Stage 3-4. Stage 4 indicates metastatic disease 17 Terminology: Remission Some cancers can return many years after treatment. For this reason, the term “Remission” is often used, rather than “cured” Remission means: There is no sign of cancer cells in the body If there are any left, they are: Too few to find Not causing any symptoms Not actively growing 18 Terminology: PALLIATION When cure is no longer possible, palliation, i.e. relief of tumour symptoms and prolongation of life, is possible in many cancers in proportion to their chemo- and radiosensitivity. There is on average: 2-18 months prolongation in median life expectancy for solid tumours 5-8 years for some leukaemias and lymphomas. However, new targeted treatment could increase this. The development of more effective chemotherapeutic drugs and better supportive care such as antiemetics has done much to reduce the side-effects of chemotherapy and to improve the cost/benefit ratio for the patient receiving the palliative treatment. 19 MODES OF THERAPY The method of treatment will largely be determined by a realistic assessment of the therapeutic goal and the type of cancer present. The usual modes used are:- Surgery - excision of primary tumour. Bone marrow transplantation - for some leukaemias. Radiotherapy Drugs - cytotoxic chemotherapy, hormone therapy, immunotherapy. As malignant neoplasms invade the surrounding tissues it is hard to surgically remove all of the cancer, and adjuvant therapy is normally required (e.g. radiotherapy for local invasion and lymph node spread, drugs for more disseminated cancers). Two factors govern which treatment to use – i) empirical clinical evidence; ii) practical considerations 20 MODES OF THERAPY 1. Surgery Well-defined solid tumour Non-vital region (e.g. mastectomy) Non-mutilating result Resection/reconstruction possible (e.g. gut) Palliation (relieve symptoms) 2. Radiotherapy Diffuse but localized tumour (e.g. lymphoma) Vital organ / region (e.g. head and neck, CNS) Adjuvant therapy (e.g. post mastectomy) Palliation 3. Chemotherapy Adjuvant therapy (following initial treatment: surgery or radiotherapy) Neo-adjuvant (therapy prior to surgery or radiotherapy) Widely disseminated / metastasized Diffuse tumour (e.g. leukaemia) Palliation Some primary tumours (e.g. Hodgkin’s lymphoma) NEWER Targeted therapy- monoclonal antibodies Personalized medicine 21 SURGERY Often a Firstline treatment: Curative: Excise the cancer with limited side effects (when feasible) Mitigation – reduces tumour size and used with other treatments Palliative: reduce symptoms (obstructing or effecting other organs functions) Preventative – remove pre-cancerous tissues 22 TREATMENT OF CANCER: CHEMOTHERAPY AND RADIOTHERAPY Radiotherapy is the application of ionizing radiation to treat disease - electromagnetic radiation and elementary particles deposit energy in materials through the processes of excitation and ionization events. Chemotherapeutic agents exert their effect by killing cells that are rapidly dividing. The agents are therefore NOT tumour specific but also kill normal rapidly dividing cells such as hair follicle cells and gastrointestinal mucosa. 23 Focus on chemotherapy Major cancer treatment Drugs to dispense 24 RATIONALE OF CHEMOTHERAPY Systemic treatment Most commonly used to treat advanced cancer. In a limited number of cases, it is the sole treatment for cancer (e.g. chemosensitive cancers such as leukaemia). For the majority of the solid tumours, chemotherapy is used to reduce the volume of disease, and the palliative symptoms caused by cancer. A further indication for chemotherapy is to use it as an adjuvant after the primary tumour has been controlled by either surgery or radiotherapy - this is to eradicate subclinical micrometastatic disease and reduce the risk of recurrence. Neoadjuvant chemotherapy is also used increasingly to debulk or downstage primary tumours prior to the definitive treatment, eg surgery or radiotherapy. Chemotherapy is usually used systemically either intravenously or orally. 25 RATIONALE OF CHEMOTHERAPY To understand the rationale of cytotoxic chemotherapy it is important to recognise the features of tumour growth - factors responsible for determining the growth of a tumour include the cell cycle time, growth fraction, number of cells. By the time tumours are clinically apparent (around 10 9 cells or more, 1cm, average doubling time 110 days) most tumours are in the relatively slow phase of growth - this is the time that chemotherapeutic agents are least likely to prove effective. Chemotherapeutic agents are used in combination rather than as sequential single therapies. The combination of drugs chosen should have a minimal overlap in toxicity. Reduced toxicity to patient but improved cancer cell killing). The treatment should be delivered on an intermittent basis with the shortest possible time between treatments that allows recovery of the most sensitive normal tissue (e.g. bone marrow or gut). 26 RATIONALE OF CHEMOTHERAPY Wherever possible it is preferable to use drugs with known synergistic killing effects (for example the combination of oxaliplatin and 5-fluorouracil – better patient outcome in combination) Combination of drugs that can kill cancer cells at different stages of the cell cycle. Some regimens use alternating cycles of different drug combinations - giving the less effective drug first (but possibly least toxic) 27 MEASURING RESPONSE TO TREATMENT A measurable response to treatment can serve as a useful early surrogate marker when assessing whether to continue a given treatment for an individual patient. Definitions of responses:- Complete response: complete disappearance of all detectable disease. Partial response: More than 50% reduction in the product of the bi-dimensional diameters of the tumour Stable disease: No change, or