3 - Treatment Principles Flashcards
1
Q
What three factors determine the rate of tumour growth?
A
- Growth fraction: proportion of all cells in the cell cycle
- Length of cell cycle
- Rate of cell loss
2
Q
What information do patients usually want to know the most about cancer treatment?
A
- Side effects?
- What are the treatment aims? e.g. curative or palliative
- Does it work? e.g. response rates and resistance
- What does the treatment involve?
3
Q
What do the following terms mean in cancer treatment:
- Radical/Curative
- Palliative
- Adjuvant
- Neo-adjuvant
- Maintenance therapy
A
- 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
4
Q
What is the difference between supportive care, palliative care and end of life care?
A
Supportive
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
End-of-life
Treatment in final stages e.g. pain relief
5
Q
What do we need to know before deciding a treatment plan for cancer?
A
Staging
Performance status
Always include patient in decision making process and use MDT
6
Q
What is staging used for?
A
Assess local and distant disease
Determines how operable the cancer is and what treatment should be used
7
Q
What are the different aims of surgery in cancer treatment?
A
- 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
8
Q
What are some of the different aims of chemotherapy?
A
- Primary: e.g haematological malignancies
- Neoadjuvant
- Adjuvant
- Palliative
9
Q
What is the principle of chemotherapy?
A
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
10
Q
What are the 4 classes of cancer drugs?
A
- Cytotoxic
- Hormones
- Kinase inhibitors
- Monoclonal antibodies
11
Q
What are the 4 classes of cytotoxic drugs?
A
Anthracyclines
Doxorubicin
Anti-metabolics
Methotrexate
Fluorouracil
Alkylating agents
Cisplating
Cyclophosphamide
Plant derivatives
Paclitaxel
Vinorelbine
12
Q
What is the mechanism of action of alkylating agents?
A
Alkylating agents
Alkylating agents react with DNA bases and produce a cross link which covalently bonds the two DNA strands
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
13
Q
What is the MOA of the anti-metabolites methotrexate and 5-fluorouracil?
A
5FU (Colorectal, Breast, Gastric):
Thmidylate synthase inhibitor
Blocks syntehsis of thmidine which is needed for DNA replication
Methotrexate (Colorectal, Lung, Gastric):
Competitively inhibits dihydrofolate reductase
Needed for tetrahydrate folate syntehsis
14
Q
How do vinca alkaloids act as chemotherapy agents?
A
Disrupt spindle fibres so cells cannot undergo mitosis
15
Q
What is the mechanism of action of taxanes?
A
Stop microtubule formation
16
Q
What is the mechanism of action of Doxorubicin (antibiotic)
A
Stops topoisomerase action
17
Q
What does a high number of epidermal growth factor receptors in cancer indicate?
A
Poor prognosis
18
Q
What are some mechanisms of chemotherapy drug resistance?
A
- Decreased entry or increased exit of agent
- Inactivation of agent in cell
- Enhanced repair of DNA damage
19
Q
What is growth fraction?
A
Proportion of cells which are actively proliferating
Larger the tumour the smaller the growth fraction
20
Q
What is the relevance of the growth fraction in chemotherapy treatment?
A
- 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
21
Q
What is the fractional kill cell hypothesis?
A
Dose kills a constant proportion of tumour cells rather than a constant number
Need repeated doses
22
Q
What is the highest to lowest chemosensistive cancers?
A
23
Q
What are some cell cycle specific chemotherapy drugs?
A
24
Q
What are some cell cycle non-specific chemotherapy drugs?
A
25
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**
26
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
27
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 are and monitor. Contact plastic surgeons early
* Report to National Extravasation scheme
28
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
29
What are the patterns of emesis with chemotherapy drugs?
**Acute 4-12 hours**
**Delayed 2-5 days**
**Chronic up to 14 days**
30
What are some skin changes with chemotherapy?
* Irritation and thrombophlebitis of veins
* Extravasation
* Hyperkeratosis
* Hyperpigmentation
* Ulceration
31
How does mucositis from chemotherapy present?
Can affect the whole GI tract
* Sore mouth
* GI bleed
* Diarrhoea
32
What chemotherapy drugs cause cardiotoxicity and how?
**Cardiomyopathy**: doxorubicin, high dose cyclophosphamide
**Arrhythmias:** cyclophosphamide, etoposide
33
What chemotherapy drugs are known to cause pulmonary fibrosis?
* Bleomycin
* Mitomycin C
* Cyclophosphamide
34
What factors affect the predicted response of a chemotherapy drug?
- Performance status
- Clinical stage
- Prognostic factor
- Molecular or cytogenetic factors
35
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
36
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
37
Why is every patient's chemotherapy dose individualised?
- Different therapeutic indexes
- Side effects
- Can the drug be handled e.g. liver and refnal function
- Patient wellbeing e.g. performance status and comorbidity
- BMI or surface area
38
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
39
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
40
What monitoring is done during chemotherapy treatment?
* Response of cancer
* Drug levels
* Check for organ damage
41
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 vivo*requires the patient’s immune system to be able to respond upon challenge
42
What are the different classifications of immunotherapy?
**Checkpoint inhibitors** most common
43
What is the mechanism of action of the following immunotherapy:
1. Checkpoint inhibitors
2. Adoptive cell therapy
**Check points inhibitors**
Check points are receptors on T cells
Suppress T cell immune response to prevent T cells from attacking normal cells, this means cancer cells can be targeted by T cells
**Adoptive cell therapy:**
T cells removed and isolated from patient, they are modified and then put back in
44
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
45
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
46
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)
47
What are the skin side effects of immunotherapy?
- Immune-related dermatitis
- Pruritus
- Dry skin
- Rash (Stevens-Johnson syndrome or toxic epidermal necrolysis)
48
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
49
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
50
What are some of the side effects of monoclonal antibodies? (specifically EGFR inhibitors)
Acneiform rash and Diarrhoea
(same as immunotherapy)
51
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
52
What are some of the psychosocial side effects of chemotherapy?
PTSD
Financial burden
Depression
Employment difficulties
Social isolation
Emotional difficulties
Strained relationships
53
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
54
What are the side effects of hormone therapy?
Dependent on the hormone they are blocking
55
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
56
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’
57
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
58
What are the intentions of radiotherapy?
* Palliative
* Curative
59
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**
60
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
61
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**
62
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
63
What are some risk factors that increase the risk of certain long term side effects of chemotherapy?
* Younger means more chance of secondary malignancy
* Infertility if older and more cumulative dosing
64
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
65
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
66
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
67
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
68
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
