Systemic Cancer Management Flashcards
Antimetabolites are a class of chemotherapy drug. How do they work?
Target S phase of cell cycle
Antagonises folic acid/purine synthesis or pyrimidine synthesis
Prevents either Thymidine or Nucleotide formation
Generally affects synthesis phase of other rapidly dividing cells
Give three examples of Antimetabolite agents and a common use
Methotrexate (inhibits dihydrogen folate reductase) - Leukaemia
Mercaptopurine - Acute Leukaemias
5FU - Wide Range
Give four examples of anti tumour antibiotics
Dactinomycin
Doxorubicin
Bleomycin
Mitomycin C
Give a use and a side effect of Doxorubicin
Breast Cancer
Permanent Cardiotoxicity
Give a use and a side effect of Bleomycin
Testicular Cancer
Pulmonary Toxicity
Give a use and a side effect of Mitomycin C
Intravesicle bladder cancer
Myelosupression
What is an Alkylating agent?
Alkyl groups interact with and cross link DNA
Can be monofunctional or bifunctional depending if one or two alkyl groups
Name two examples of Alkylating agents and their respective side effects
Mechlorethamine - Myelosupression
Cyclophosphamide - Haemorrhagic Cystitis
What are Anti-Microtubule agents? Describe the broad subtypes
Disrupt mitotic spindle disruption (targeting M phase)
Vinca Alkaloids - Blocks polymerisation of microtubules and stops mitotic metaphase
Taxanes - Promote and overstabilise microtubules which then becomes dysfunctional
Give an example of a Vinca Alkaloid and a side effect
Vincristine
Neurotoxicity
Give an example of a Taxane
Docetaxel
How do Platinum Agents work? Give an example
Similar to Alkylating agents as they cross link DNA
Cisplatin
How to Topisomerase work?
Inhibits nuclear enzymes which normally decline the supercoils in DNA to allow replication
Targets S Phase
Give two examples of Topisomerase inhibitors and respective uses
Irinotecan - Metastatic Colon Cancer
Etopiside - Lymphoma
Name four subtypes of Hormonal Therapies
SERM
Aromatase Inhibitors
GnRH Agonists
GnRH Antagonists
How are Glucocorticoids used as a Hormonal Therapy?
Can be used in combination for leukaemias and lymphomas
Reduces lymphoid mass and increases lymphocyte breakdown
How do SERMs work?
Can be an agonist, antagonist or partial agonist against oestrogen receptors
Tamoxifen is an antagonist in breast tissue
Tamoxifen is an agonist in endometrium
Raloxifene is a partial agonist in breast only
What is an Aromatase Inhibitor?
Post menopausal women produce a lot of oestrogen via aromatase pathway, which this inhibits
SE: Hot Flush, Reduced Bone Density
What are GnRH Agonists?
Eg Goserelin
Used for prostate cancer, constant stimulation of GnRH leads to desensitisation
Leads to an initial androgen flare
How are androgen flares treated during GnRH agonist therapies?
Anti Androgens such as Flutamide
Name a GnRH ANTagonist and give two side effects
Degarelix
Hot flushes
Impotence
How can biological/targeted therapies kill cancer cells?
Block cell surface receptors Receptor Ligand Induce Immune Cells Activating complement system Delivering chemo straight to cancer cells
What is Herceptin? Give a side effect
Used in HER2 positive breast cancers
IgG Antibody that blocks receptor
Risk of Cardiotoxicity
What is Cetuximab? Give a Side Effect
A Mab that binds to VEGF used for metastatic colon cancer
Side effect is bleeding
What is Imatinib? Name a side effect
Tyrosine Kinase inhibitor active against BCRABL and used in CML
SE:Myelosupression
Biological/Targetted therapies can present with infusion reactions. How does it present?
Fever
Chills
Nausea
Other than infusion reactions, name some side effects of biological therapies
Haemolytic Anaemia
Eosinophilia
Hepatitis/Dermatitis/Neuropathies
Often reversible with steroids
What is Chemotherapy?
Systemic therapy used to kill cancer cells by causing apoptosis or cytotoxicity
Targets rapidly dividing cells
Can be cell cycle specific or cell cycle non specific
Name five different uses of Chemotherapy
Induction therapy
Neoadjuvant to shrink before surgery/radio
Adjuvant (after surgery/radio)
Maintenance in lower doses (maintain remission)
Palliative (addressing symptoms)
How is dosing of chemotherapy calculated?
Based on patients surface area
Cycles need to be the correct length to allow healthy cells to recover (but not cancer cells)
Name seven common side effects of chemotherapy
Alopecia Nausea and Vomiting Neutropenia Oral Mucositis Weight Loss Peripheral Neuropathy Secondary Cancers
Describe the side effect ‘Alopecia’ in Chemotherapy
Onset usually 7-10 days after chemotherapy
Managed with wigs and reassurance that it will return
Describe the time frame of side effect ‘Nausea’ in Chemotherapy
Acute - within a few hours
Delayed - more than 24 hours
Anticipatory - conditioned response
Describe the non pharmacological management of CINV
Small light meals several times a day
Dry Starchy food
Avoid vestibular stimulation
Sleep
Describe the pharmacological options for management of CINV
Ondansetron
Aprepitant
Dexamethasone
Olanzepine
Describe the side effect ‘Neutropenia’ in Chemotherapy
Neutrophils <1.5 (or <0.5 if severe)
Can consider G-CSF as prophylaxis
Antibiotics and sepsis 6 if any suspicion of neutropenic sepsis
Describe the side effect ‘Oral Mucositis’ in Chemotherapy
Inflammation or ulceration of oropharyngeal mucosa which can interfere with eating/swallowing/speech
Onset peaks 7d after chemotherapy
Describe the non pharmacological management of Oral Mucositis
8-12 cups of fluid
Avoid Spicy/Acidic Foods
Maintain good oral hygiene
Cryotherapy (such as ice chips)
Describe the pharmacological management of Oral Mucositis
Mouth Rinses (not containing alcohol)
Describe the management side effect ‘Weight Loss’ in Chemotherapy
Small frequent meals and nutrient supplementation
Define Cachexia
Hypercatabolic state leading to weight loss despite nutritional supplementation
Describe the side effect ‘Peripheral Neuropathy’ in Chemotherapy
Stocking and glove distribution
Managed by changing/adjusting dose, and trialing Gabapentin/Duloxetine
What are the common secondary cancers
Myelodysplastic Syndromes
Acute Myeloid Leukaemia
What is Radiotherapy?
Electromagnetic spectrum used to treat cancer (normally in XRay/Gamma Ray range)
It works by causing direct damage to DNA and or Indirect damage (by radical formation)
Targets rapidly dividing cells in M phase
What are the four Rs that affect the efficacy of Radiotherapy ?
Repair of DNA by the cell (using fractionation wisely)
Repopulation of tumour cells in between fractions
Reassortment (solved by giving over many fractions to ensure all cells have been hit in M Phase)
Reoxygenation (cells further away from O2 supply are less radiosensitive)
What are the three types of Radiotherapy?
External Beam Radiotherapy
Brachytherapy
Stereotactic Radiosurgery
What is Brachytherapy?
Radioactive pellets inserted into tumour either temporarily (HDR) or permanently (LDR)
What is Stereotactic Radiotherapy?
Uses either linear accelerators or specialises gamma knife
What investigations are used to mark out tumour size and volume?
CT
PET
How is chemotherapy often useful as a Radiotherapy adjunct?
It can be used as a radiosensitiser
How can Radiotherapy be used palliatively?
Bone Mets Lung Mets Brain Mets Spinal Cord Compression SVCO
Lymphoedema is one of the long term complications of systemic therapy. What is it?
Swelling due to the obstruction of lymph fluid outflows causing build up in tissues
Progresses over two to four years causing pitting/thickening/achiness
How is the severity of Lymphoedema determined?
Difference in circumference between affected and unaffected limb
Stage 1: 2-3cm difference
Stage 2: 3-5cm difference
Stage 3: >5cm difference
Give one protective factor and one risk factor for Lymphoedema
Protective - Good skin care
Risk - LN dissection
How is Lymphoedema managed?
Avoid tight clothes
Compression
Physio
Radiation dermatitis and fibrosis is one of the long term complications of systemic therapy. What is it?
Fibrotic transformation due to repeated inflammation and healing
Can result in skin thickening, ulcers, dysphagia and urethral strictures
How can radiation dermatitis/fibrosis be avoided?
Loose fitting clothes
Unscented water based moisturisers avoided pre therapy
Topical steroids after each session
Describe the effect of chemotherapy on fertility
Can affect central or peripheral pathways
Can reduce sperm count
Chemotherapy is less toxic to oocytes than to follicular development (meaning temporary Amenorrhoea rather than early menopause)
How does Radiotherapy affect fertility?
More damaging than chemotherapy
Can affect implantation as well as eggs/sperm
How can fertility in systemic therapy be managed?
Pre-emptive preservation
Administering preserving medications during therapy
How is Neuropathy secondary to chemotherapy managed?
Physiotherapy
Electrostimulation
Neuropathic Pain drugs
How does Chemotherapy affect cognition and memory?
Chemotherapy- generally mild but can persist for months/years after
How does Radiotherapy affect cognition and memory?
Biphasic
Temporary decline followed by permanent decline
