3 - Treatment Principles Flashcards
What three factors determine the rate of tumour growth?
- Growth fraction: proportion of all cells in the cell cycle
- Length of cell cycle
- Rate of cell loss
What information do patients usually want to know the most about cancer treatment?
What do the following terms mean in cancer treatment:
- Radical/Curative
- Palliative
- Adjuvant
- Neo-adjuvant
- Maintenance therapy
- Radical/Curative: Vigorous treatment that aims at the complete cure rather than the mere relief of symptom
- Palliative: Treatment given to relieve symptoms and reduce suffering, no aim to cure
- Adjuvant: Additional cancer treatment given after the primary treatment to lower the risk that the cancer will come back
- Neo-adjuvant: Treatment given as a first step to shrink a tumor before the main treatment so not as major a surgery
- Maintenance therapy: Treatment that is given to help keep cancer from coming back after it has disappeared following the initial therapy
What is the difference between supportive care, palliative care and end of life care?
Supportive is throughout cancer journey e.g treating tumour lysis syndrome, managing side effects
Palliative does not mean end of life is imminent, just means disease is incurable
What do we need to know before deciding a treatment plan for cancer?
STAGING + PERFORMANCE STATUS
Always include patient in decision making process and use MDT
What are the different aims of surgery in cancer treatment?
- Diagnostic: e.g sentinel node biopsy
- Staging: laparoscopically
- Radical/curative: most common aim
- Neoadjuvant/adjuvant: debulking of primary tumour
- Palliative: to relieve symptoms if metastatic e.g stenting blockage, fixing bones
- Supportive: e.g vascular access like a Port a Cath
- Reconstructive: e.g after mastectomy
- Prophylactic: e.g BRCA1/FAP
Not preferred for early stage cancers
What are some of the different aims of chemotherapy?
- Primary: e.g haematological malignancies
- Neoadjuvant
- Adjuvant
- Palliative
What is the principle of chemotherapy?
Chemotherapy interferes with replicating cell cycle so cancer cell becomes damaged and undergoes apoptosis
Tends to only effect cancer cells as they are highly proliferative so in the cell cycle more than healthy cells
What are the different classes of cytotoxic chemotherapy drugs and how do they work? (give an example of each)
- Alkylating agents (e.g Cyclophosphamide): anti proliferative drugs that bind alkyl groups to DNA
- Antimetabolites (e.g Methotrexate and 5-Fluorouracil): Interfere with cell metabolism of nucleic acids
- Vinca alkaloids (e.g Vincristine): spindle poisons
- Antibiotics (e.g Doxorubicin)
- Monoclonal antibodies: inhibit a specific process e.g angiogenesis or epidermal growth factor receptors
What is the mechanism of action of alkylating agents and platinum compounds?
Alkylating agents
- Alkylating agents react with DNA bases and produce a cross-link that covalently links the two strands of the DNA double helix
- Unless repaired, this lesion will prevent the cell from replicating effectively
Platinum Compounds
Formation of platinated inter and intrastrand adducts, leading to inhibition of DNA synthesis
What is the MOA of the anti-metabolites methotrexate and 5-fluorouracil?
5FU (Colorectal, Breast, Gastric): thymidylate synthase (TS) inhibitor,blocks synthesis of the pyrimidine thymidine, which is a nucleoside required for DNA replication
Methotrexate (Colorectal, Lung, Gastric): competitively inhibits dihydrofolate reductase (DHFR), an enzyme that participates in the tetrahydrofolate synthesis
How do vinca alkaloids act as chemotherapy agents?
Disrupt spindle fibres so cells cannot undergo mitosis
What is the mechanism of action of taxanes?
Stop microtubule formation
What is the mechanism of action of Doxorubicin (antibiotic)
Stops topoisomerase action
What does a high number of epidermal growth factor receptors in cancer indicate?
Poor prognosis
What are some mechanisms of chemotherapy drug resistance?
- Decreased entry or increased exit of agent
- Inactivation of agent in cell
- Enhanced repair of DNA damage
What is the relevance of the growth fraction in chemotherapy treatment?
- Higher growth fraction the more responsive a tumour is to chemotherapy
- Reason for multiple cycles, to catch cells that may have been dormant in first cycle
- Growth fraction depends on size of tumour and type of cancer
What is the fractional kill cell hypothesis?
What is the highest to lowest chemosensistive cancers?
What are some cell cycle specific chemotherapy drugs?
What are some cell cycle non-specific chemotherapy drugs?
What are some of the immediate chemotherapy side effects? (occurs in minutes)
•Extravasation: leakage of chemotherapy to the adjacent tissue
•Facial/body flushing
•Cardiac Arrhythmias
•Hypotension
•Hypersensitivity
•Anaphylaxis
•Haemorrhagic cystitis
What are some of the short term side effects of chemotherapy (hours to 7 days)?
- Nausea and vomiting
- Constipation
- Diarrhoea
- Fatigue
- Discolouration of urine
- Mucositis
- Tumour lysis syndrome
How can extravasation of chemotherapy drugs be managed?
- Do not use IV line if unsure about patency
- Stop infusion, disconnect drip and aspirate any remaining drug from cannula before removing cannula
- Apply cold pack if DNA binding drug to vasoconstrict, heat pack if non-DNA binding drug to vasodilate and distribute
- Elevate arm and mark affected area and monitor. Contact plastic surgeons early
- Report to National Extravasation scheme
What are the long term side effects of chemotherapy?
- Bone marrow suppression (neutropenia)
- Liver dysfunction
- Renal toxicity
- Cardiac toxicity
- Pulmonary fibrosis
- Peripheral neuropathy
- Changes in fertility
- Neutropenic sepsis
What are the patterns of emesis with chemotherapy drugs?
What are some skin changes with chemotherapy?
- Irritation and thrombophlebitis of veins
- Extravasation
- Bleomycin: hyperkeratosis, hyperpigmentation, ulcerated pressure sores
- Doxorubicin, cyclophosphamide: Hyperpigmentation
How does mucositis from chemotherapy present?
Can affect the whole GI tract
- Sore mouth
- GI bleed
- Diarrhoea
What chemotherapy drugs cause cardiotoxicity and how?
Cardiomyopathy: doxorubicin, high dose cyclophosphamide
Arrhythmias: cyclophosphamide, etoposide
What chemotherapy drugs are known to cause pulmonary fibrosis?
- Bleomycin
- Mitomycin C
- Cyclophosphamide
What factors affect the predicted response of a chemotherapy drug?
Why do we give combination chemotherapy?
- Increases tumour cell kill so improved overall response
- Also helps reduce the mechanism of resistance
- Need to balance this with the side effects/safety
What are the different routes of administrations of chemotherapy?
- IV:most common e.g bolus, infusional bag, continuous pump infusion
- PO convenient, dependent on oral bioavailability
–SC convenient in community setting
–Into a body cavity – bladder, pleural effusion
–Intralesional - directly into a cancerous area, consider pH
–Intrathecal - into the CSF – by lumbar puncture
–Topical -medication will be applied onto the skin
–IM rarely
Why is every patient’s chemotherapy dose individualised?
•Narrow therapeutic indices
•Significant side effect profile
•Surface area and/or body mass index
• Drug handling ability (eg liver function, renal function)
• General wellbeing (performance status and comorbidity)
What are some drug interactions with the following chemotherapy agents?
- Vincristine
- 5FU
- Methotrexate
- Vincristine: itraconazole (a commonly used antifungal) leads to more neuropathy
- Capecitabine (oral 5FU): warfarin, St John’s Wort, Grapefruit juice
- Methotrexate: penicillin and NSAIDs
What are some specific chemotherapy side effects in lymphoma and AML?
- Acute renal failure from tumour lysis syndrome
- GI perforation for lymphoma
- DIC for AML
What monitoring is done during chemotherapy treatment?
- Response of cancer
- Drug levels
- Check for organ damage
How does immunotherapy work?
Uses the immune system and its components to recognize, target and destroy cancer cells
Passive: ex vivo-activated cells or molecules that once found inside thebody, compensate for missing or deficient immune functions
Active: stimulates effector functions in vivorequires the patient’s immune system to be able to respond upon challenge
What are the different classifications of immunotherapy?
Checkpoint inhibitors most common
What is the mechanism of action of the following immunotherapy:
- Checkpoint inhibitors
- Adoptive cell therapy
Adoptive cell therapy: T cells removed and isolated from patient, they are modified and then put back in
Give some examples of checkpoint inhibitors.
- *CTLA4 inhibitor (on T cells)**
- Imipilumumab
- Used in Melanoma
- *PD-1/PD-L1 inhibitors (on B cells)**
- Nivolumab
- Pembrolizumab
- Used in melanoma, lung, renal cancers
What is the mechanism of action of the following immunotherapies:
- Cytokines
- Oncolytic virus therapy
Oncolytic virus therapy: virus will infect the cancer cell and replicate itself. This results in destruction of the cancer cell, releasing the tumour antigens and activating antibodies. T-cells will be activated and generates antitumor response causing the cancer cell to die
What are the side effects of immunotherapy?
(important card)
Can occur up to months after treatment, usually around 6-8 weeks incidence, safety monitoring tests need to be done
ORGANITIS
- Rash
- Pneumonitis
- Colitis/Diarrhoea
- Immune related hepatitis
- Nephritis
- Myalgia/Arthralgia
- Endocrine abnormalities (hypothyroidism, hypopituitarism)
What are the skin side effects of immunotherapy?
- Immune-related dermatitis
- Pruritus
- Dry skin
- Rash (Stevens-Johnson syndrome or toxic epidermal necrolysis)
What is molecular targeted therapy for cancer treatment?
Monoclonal antibodies
Bind to a certain antigen on cancer cell surface, blocking specific downstream signaling pathways and arresting cell proliferation
Give three examples of targeted therapy in cancer treatment.
- HER2 inhibitor e.g. Herceptin/Trastuzumab in breast and gastric cancers
- VEGR (vascular epithelial growth receptor) inhibitors e.g. Bevacizumab in ovarian & bowel cancer
- EGFR inhibitor (epithelial growth factor receptor) e.g. Cetuximab/Panitumumab in bowel cancer
What are some of the side effects of monoclonal antibodies? (specifically EGFR inhibitors)
Acneform rash and Diarrhoea
(same as immunotherapy)
How do you treat an acneiform rash as a side effect of EGFR inhibitors?
Long term oral steroids often required to treat most side effects of immunotherapy drugs
What are some of the psychosocial side effects of chemotherapy?
What are some hormone therapies for cancer treatment and what is the principle of hormone therapy?
Some cancers depend on hormones (dihydrotestosterone for prostate and oestrogen for breast) to grow so block these hormones
- Aromatase Inhibitors: used in post menopausal women for breast cancer
- SERMs: Tamoxifen for breast cancer
- GnRH agonists: Goserelin (Zoladex) for prostate cancer
What are the side effects of hormone therapy?
Dependent on the hormone they are blocking
What is the mechanism of action of radiotherapy in cancer treatment?
High energy ionising radiation (x-rays) causes cell DNA damage by free radicals and cell death
Can be used alone or as an adjunct to surgery/chemo
50% of cancer patients would benefit from this
What are the different types of radiotherapy?
- External Beam (most common)
- Stereotactic
- Brachytherapy (prostate and cervical cancer, implant)
- Systemic treatments: Radioactive substance (injected/swallowed)
Aim to:
- Deliver the highest dose possible to the tumour
- Minimise dose to surrounding ‘normal tissue’
What is a radiosensitiser and give some examples?
Drugs that can enhance the killing effect on tumor cells by accelerating DNA damage and producing free radicals indirectly
Usually chemo drugs
What are the intentions of radiotherapy?
- Palliative
- Curative
What are some early side effects of radiotherapy (up to 8 weeks)?
Side effects are from healthy cells being damaged by the radiation.
Depends on site of radiation!
- Tiredness
- Fatigue
- Skin reactions: from erythema to desquamation
- Alopecia
- Lymphoedema
- Mucositis: diarrhoea, dysuria, mouth sores
- Nausea and vomiting
- Dysphagia
- Cystitis
- Bone marrow suppression
How are the following side effects of radiation managed?
- Mucositis
- Cystitis
- Skin erythema
- Mucositis: avoid smoking, alcohol and spicy food. Aspirin gargle. Nystatin for thrush
- Cystitis: after pelvic treatments drink lots of fluids and NSAIDs
- Skin: moisturisers
What are some late side effects of radiotherapy? (months to years)
Think about effect of fibrosis in different areas of body
- Skin pigmentation changes
- Pulmonary fibrosis
- Infertility
- Secondary cancers (usually sarcoma)
- Constrictive Pericarditis
- Fistulas
- Urinary frequency
- ED
- Panhypopituitarism
- Hypothyroidism
- Cataracts
What are some steps you can take to lower the rates of infertility with cancer treatment?
- Goserelin during chemotherapy for women
- Semen cryopreservation
- Testicular sperm extraction
- Cryopreservation of embryos
- Ovarian tissue banking
Harder in women as need ovarian stimulation and oocyte collection which results in unacceptable delays to treatment
What are some risk factors that increase the risk of certain long term side effects of chemotherapy?
- Younger means more change of secondary malignancy
- Infertility if older and more cumulative dosing
How do you explain to a patient the difference between chemotherapy and targeted therapy?
Chemo will affect all cells, even healthy ones so more side effects
What is the difference between proton beam therapy and classical radiotherapy?
Proton beam therapy stops the x-rays travelling through the tumour to the tissue behind it
Minimises damage to healthy cells so less side effects
What are some of the challenges of survivorship after cancer has been treated?
Often no aftercare system for all of these issues and have to adapt to a new life
- Long term side effects of treatment
- Chronic fatigue
- Breathlessness
- Difficulties eating
- Incontinence and bowel problems
- Anxiety, panic attacks, or depression
- Health anxiety about recurrence
- Pain
- Change in relationships
- Returning to work
How do Macmillan suggest cancer survivorship can be improved?
- Earlier diagnosis
- Access to the best available treatment, regardless of age alone or where you live in the UK
- A ‘Recovery Package’ of care and support for everyone diagnosed with cancer
- Increased physical activity
What is a specific side effect of the following drugs:
- Anthracyclines and anti-HER2
- Platinum agents
- Cyclophosphamides
- Tamoxifen
- Bleomycin
- Cytarabine
- Anthracyclines (doxorubicin, daunorubicin) and anti-HER-2 monoclonal antibodies (e.g. Herceptin): cardiomyopathy
- Platinum agents (cisplatin, carboplatin): peripheral neuropathy, sensorineural hearing loss, nephrotoxicity
- Cyclophosphamides: haemmorhagic cystitis and TCC of bladder
- Tamoxifen: risk of endometrial cancer
- Bleomycin: lung fibrosis
- Cytarabine: ataxia
