Systemic Anti-Cancer Therapy: Intro to Oncology

• Systemic Anti-Cancer Therapy (SACT) covers the Clinical Pharmacology of cancer treatment.

Learning Outcomes - Lecture One:

• Identify the most common cancers in the UK population
• Understand cancer service provision in Northern Ireland
• Recognize the red flag warning signs or common cancers
• Understand cancer terminology related to staging and prognosis
• Describe the pathway from cancer diagnosis to treatment choice
• Understand the influence of cancer biomarkers on treatment choice

What is Cancer?

• Cancer arises from a deviation from the normal cell process, leading to uncontrolled growth because of DNA damage
• DNA damage can be avoidable and unavoidable
• Avoidable causes may be smoking, asbestos exposure, and excessive sun exposure
• Unavoidable causes may be increasing age and hereditary gene disturbances
• DNA damage can cause cells to deviate from their normal process and ignore apoptosis signals
• Tumors form from the accumulation of cancer cells, attracting white blood cells and forming their own blood supply
• Cancer cells can travel via the bloodstream/lymph nodes, creating metastases
• Normal cell growth and division should be under careful control in healthy cells

Hallmarks of Cancer

• Mutations affect cell growth and division.
• Errors in DNA replication can persist.
• This changes cell behavior, leading to uncontrolled growth.
• There are now ten hallmarks of cancer.
• Cancer treatments target these differences to eradicate cancer cells
• Cancer cells can avoid death and continue to replicate

Cancer Statistics

• Cancer is a widespread disease, with over 3 million people in the UK living with it
• Every two minutes someone in the UK is diagnosed with cancer
• More than 200 types of cancer exist, the four most common in the UK are breast, lung, prostate, and bowel
• The Department of Health created a cancer registry in 1994
• Individuals have a one in two chance of developing cancer before age 85
• Cancer affects the entire population
• More than 13,000 patients are diagnosed annually in Northern Ireland
• Aside from melanoma, the most common cancers are breast and prostate

NHS Cancer Centres in N.I.

• Patients with common cancers can receive treatment at their local hospital
• Haematological, breast, bowel, and prostate cancer services are provided across all 5 trusts in N.I.
• Rarer cancers are treated at tertiary cancer centers like Belfast City Hospital (BCH) and Altnagelvin Hospital (NWCC)
• Radiotherapy is available at BCG and NWCC
• Stem cell transplant services are offered at BCH
• Local aseptic units prepare SACT

Northern Ireland Cancer Network (NICAN)

• It is a strategic clinical network.
• It provides clinical management guidelines.
• It links cancer care organizations.
• It ensures uniformity of quality in cancer care.
• Regionally shared SACT protocols are implemented.
• It is vital for everyone involved in cancer care.
• Regular meetings are held via Clinical Reference Groups.
• It ensures evidence-based cancer services.
• Focuses on equity of access

Signs and Symptoms

• Refer to the provided images for the signs and symptoms of breast and lung cancer
• Prostate cancer often develops slowly with few early signs

Prostate Cancer Information

• Prostate cancer in males is the most common type with the highest rates among men aged 75-79
• Men usually don't present with symptoms until the cancer has progressed
• The PSA test (prostate-specific antigen) can detect elevated levels potentially indicative of cancer
• Cervical screening, breast screening, and bowel screening are early cancer detection methods

Cancer Staging Systems

• Cancer stage indicates the spread of cancer and available treatment options
• TNM Staging System defines different stages:
• T = tumour
• N = nodes
• M = metastases
• The Number Staging System uses Stages 1-4 based on the spread of the cancer

Cancer Terminology

• SACT is a systemic anti-cancer therapy, it is an umbrella term for all cancer treatments available
• This includes chemotherapy and newer treatments such as immunotherapy
• Neoadjuvant treatment shrinks a tumor before surgery
• An example is chemotherapy or hormone therapy
• Adjuvant treatment uses SACT after surgery to eliminate remaining disease.
• Palliative treatment controls tumor growth and relieves symptoms but cannot cure cancer
• It is used when the disease had spread, or when they are not fit for surgery
• Biomarker testing identifies genetic alterations in cancer cells to help target treatment
• A biopsy is a sample of cells or tissue examined by a pathologist
• A PET scan is used to diagnose cancer or assess treatment response
• A PICC line is a central line inserted to deliver drugs and take blood

Cancer Treatment Pathway

• The cancer pathway guides diagnosis and treatment decisions, in the U.K. it should take 62 days from a GP appointment to first treatment

Deciding on a Cancer Treatment Plan

1. Identify the tumor type through pathological or cytological examination
2. Stage the tumor using pathology results, staging examinations, and patient-related factors
3. Identify cancer cell biomarkers
4. Assess patient performance status, age, and co-morbidities
5. Follow national guidelines
6. Multidisciplinary team (MDT) discussion
7. Consider patient preference for shared decision making

Establishing the Nature of a Tumour

• Histology and cytology determine if cells are reactive/inflammatory or neoplastic and whether they are benign or malignant
• Immunohistochemistry and next generation sequencing is used for genetic information
• Molecular pathology: examines molecule genetics

Genomics and Oncology Pharmacy Practice

• The approach is patient centred and becoming increasingly common
• Pharmacists have a key role
• It can involve somatic and germline variants
• The The National Genomics Test Directory provides guidelines
• There is a Gene panel approach
• The The Genomics Pharmacy Advisory Group advises on genomic testing
• Patients must undergo genetic testing before starting 5-FU therapy
• Family genetic variation may be tested
• Somatic variants are within the patient's cancer cells

Cancer Biomarkers

• Cancer biomarkers in clinical practice:
• Breast cancer: BRCA1/BRCA2, ER, PR, HER2
• Colorectal cancer: RAS (KRAS/NRAS), BRAF V600E
• Lung cancer: EGFR, ALK, PDL-1, HER2, BRAF, NTRKI, RET
• Cancer biomarkers help determine suitability for targeted therapies

Role of the Pharmacist in Cancer Treatment

• Recognize red flag symptoms and refer appropriately
• Prescribe SACT with clinical verification, protocols, and MDM
• Provide patient support and counseling
• Prepare SACT with dose optimization
• Manage SACT toxicity
• Research, design, develop, and test new medicines and treatments

Learning Outcomes - Lecture Two

• Define the term SACT
• Understand the role of chemotherapy, immunotherapy, hormone therapy and targeted therapy in treatment of common cancers

Systemic Anti-Cancer Therapy

• Involves the use of drugs, gene therapy, and medicinal products to treat or control cancer
• Gene therapy and Advanced Therapy Medicinal Products (ATMPs) will not be on the exam
• Types of systemic anti-cancer therapy are chemotherapy, hormone treatment, immunotherapy, and targeted therapy
• There have been advances made in cancer treatment to achieve more targeted approaches in the last 10-15 years

Chemotherapy

• It destroys remaining cancer cells post-surgery which may be used for adjuvant therapy
• There are small chemical compounds in chemotherapy- been around since 1940-50s
• Chemotherapy acts on multiplying cells, however it can be toxic to them
• It is an injection which can be given orally or topically
• Side effects of this are predictable
• Medications are prescribed to treat and prevent them

How Chemotherapy Works

• The cell cycle lasts for 20-24 hours.
• Chemotherapy acts to interfere with DNA copying, manipulation and repair, chromosomal separation, and distort or break DNA.
• Both healthy and cancer cells replicate via the same process.
• Chemotherapy drugs are effective in different stages of the cell cycle.
• The following combined chemotherapy regimens are used:
• CapOx: capecitabine and oxaliplatin
• IMDG: irinotecan with 5-FU and folinic acid
• GemCarbo: gemcitabine and carboplatin
• EC-D: epirubicin and cyclophosphamide
• ABVD: doxorubicin, bleomycin, vinblastine and dacarbazine

Chemotherapy in Cycles

• The pulsed intermittent therapy assists normal cells to recover
• Both normal and cancer cells are harmed
• Rapidly dividing cells (bone marrow, epithelial lining, mucosal or hair follicles) are affected
• Cancer cells require longer to recover than healthy cells.
• Blood and epithelial lining cells recover within 2-3 weeks, but cancer cells take longer to recover
• Therefore, most chemotherapy is given at 3-4 weekly intervals
• Chemotherapy is is given for the cell cycle because it cannot be done indefinitely

Immunotherapy

• Immunotherapy harnesses the body’s immune system to destroy cancer cells
• It works in tumors which contain healthy cells and immune cells
• There are white blood cells helping and working against the tumor
• The different types are:

1. Antibodies attach to cancer cells and the white blood cells used for hematology
2. Checkpoint inhibitors: improve T cells

Checkpoint Inhibitors

• 3. CAR T cell therapy: create new cancer fighting T cells
• Checkpoint inhibitors have the ability to coordinate with other white cells
• If they remain active for too long- can lead to a chronic inflammation
• The T-cell activity is activated then suppressed by checkpoint proteins
• When a tumor forms, the cancer cells inactivate the T-cells
• Checkpoint inhibitors are used to stop cancer cells from inactivating the T-cells
• There can be unpredictable side-effects

Hormone Therapy

• It blocks the hormone production or action in receptors
• Oestrogen is produced in the ovaries before menopause
• The block production is aromatase inhibitors
• Example: letrozole, exemetane
• Given to women post-menopausal
• A block actions of oestrogen is SERMS
• Example: tamoxifen It is effective in early and locally advanced Breast Cancer Hormone therapy is effective in approximately 70% of breast cancers, by checking oestrogen/progesterone receptors on the cancer

Prostate Cancer

• Prostate cancer is driven by testosterone, testosterone is blocked due to this- and treatment is reduced
• Can be used at all stages of prostate cancer as a combination or treatment
• It has been diagnosed early, therefore stay on there for three years
• It is late cancer, therefore stay on indefinitely
• Always ask about depot injections when you are taking a medication history

Targeted Therapy

• Can leave some resistant cells behind
• It is designed to block just one protein or process with the cancer environment
• It can be either Antibodies or Small molecules

Antibodies and Small Molecules

• Antibodies-Very precise in targeting cell surface proteins
• Small molecules- act by blocking over-active kinases

Cancer Therapies

• Targeted therapy is OD/BD dosing
• Infusion related rash
• SACT treatment should be before or after surgery
• Treatment should be determined by what stage they are at
• If they have relapsed Here is some information regarding Breastreast:Chemotherapy, Chemotherapy, and Breast: Oral Targeted Therapy

Lung Cancer Management

• Management includes smoking cessation, surgical rescission, and radiotheraphy
• The lung cancer types are nonsmall cell and small cell.

Colorectal Cancer

• Can be improved for the early stages due to radio therapy
• Has improved for metastatic stages as well.
• There is better cancer treatment for these patients by downsizing
• Chemotherapy works when selected

Questions for Lecture Two

1. What does SACT stand for, and what is its role in cancer treatment?
2. Which four main types of systemic anti-cancer therapies are used in cancer treatment?
3. Why is chemotherapy considered a mainstay of cancer treatment?
4. What are the different purposes of chemotherapy in cancer treatment?
5. How does chemotherapy work at a cellular level to kill cancer cells?
6. Why is chemotherapy given in cycles rather than continuously?
7. What are some common chemotherapy drug combinations, and for which cancers are they used?
8. What is the goal of immunotherapy in cancer treatment?
9. How do checkpoint inhibitors help in fighting cancer?
10. What are the key differences between antibodies and small molecules in targeted therapy?
11. How does hormone therapy work in treating breast and prostate cancer?
12. Why is cardiac monitoring necessary for patients receiving Trastuzumab?
13. What are the common targeted therapies used in breast cancer?
14. How is bone health managed in breast cancer patients receiving treatment?
15. What systemic anti-cancer therapy (SACT) options are available for non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC)?
16. How is colorectal cancer managed with chemotherapy, and what role does CETUXIMAB play?
17. What are the treatment options for different stages of prostate cancer?
18. Why are bisphosphonates contraindicated in patients with renal impairment?
19. What biomarkers influence the choice of treatment in lung cancer?
20. How does chemotherapy help in managing metastatic colorectal cancer?

Learning Outcomes for Lecture Three

• Understand the role of regular SACT assessments to prevent and manage toxicity, reviewed prior to starting cycles of treatment
• List common toxicities associated with SACT:
• Chemotherapy
• Immunotherapy
• Targeted therapy
• Hormone therapy
• Define SACT toxicity grading using Common Grading Criteria (CGC)- all use the same grading criteria
• Understand immunotherapy toxicity and management
• Describe medications used to treat common SACT toxicities- management and prevention

Overview of SACT Toxicity Management

• Very effective course with risks and side effects, needs risk-benefit analysis
• Patient should have formal assessment and be informed about risks and treatment
• Access to 24 hour oncology helpline- give patients quick access for services
• There is risk of neutropenic sepsis- could be fatal
• Can happen from any treatment, especially chemotherapy
• There is an acute oncology service: reviewed throughout
• There are patient alert cards

SACT Assessment

• Review at every appointment
• Cycle One: consultant oncologist- no-one else can treatment
• Other prescribers can subsequently prescribe further cycles under the consultants direction
• Review History, side-effects, and how they are coping
• Review Examination and Safety checks

Toxicity

• Includes checking infusion related to reactions, side effects, and helpline number

SACT Prescribing

• Must be clear before each prescribing round
• Must ensure the treatment is safe and working when assessing grade and toxicity

Chemotherapy Toxicity

• Extravasation exit the vein into surrounding tissue and cause necrosis- need skin graft
• Immediate: hypersensitivity, pain at injection site, urine discolouration
• Delayed (2-7 days) post treatment: bowel changes, fatigue, hair loss
• Late: fertility issues, Cardiotoxicity, pulmonary toxicity
• General toxicities of all chemotherapy:

Nausea and Vomiting

• Each SACT agent is for and is assessed for ´emetogenic potential'.
• Low risk of emesis -> high risk
• Common used agents include Metoclopramide and Dexamethasone

Risk Factors for Diarrhoea

• Can be triggered by older age and weekly schedules

Mucositis

• It is an inflammation of the mouth
• It can cause infection
• Can is caused is chemotherapy

Immunotherapy Toxicity

• Immunotherapy exhibits a different toxicity profile than chemotherapy, mainly because it overstimulates the immune system.

Tyrosine Kinase Inhibitor Toxicity

• Small molecules and oral tablets are usually long standing
• Some include GI and Cardiac

Drug Interactions

• SACT may have interactions with medication found in clinics today
• Review regular SACT assessments