Principles of cancer therapy Flashcards
What is the role of the cancer MDT?
Standardise Continuity Reduce delays Communication Recruitment to clinical trials Education
Neoadjuvant meaning
Chemo/radio given before definitive surgery/radio to optimise outcomes
Adjuvant meaning
Treatment after definitive surgery/radio to reduce recurrence
Maintenance treatment
Maintain remission or slow growth after initial treatment
Curative treatment
Aims for no detectable cancer after treatment
Usually means a systemic treatment because of micro-mets
Palliative treatment
To relieve sx + improve QoL, can affect prognosis but not lead to cure
Performance status
0-asymptomatic
1-fully mobile but restricted in strenuous activity
2-mobile, self-care, but can’t do work activities, in bed <50% of the day
3-limited ability t self-care, in bed/chair >50% of the day
4-completely disabled, not able to self-care
5-dead
How can cancer cells acquire resistance to chemo?
- Efflux pumps
- Reduced drug uptake
- Increased drug metabolism
- Alteration of cell cycle checkpoints
- Impaired apoptosis
- Altered drug target morphology
How do they try to prevent chemo resistance?
- Combination of drugs based on action + not overlapping toxicities
- Some toxicity permissible as need maintained doses when cure realistic
Why are bone marrow cells very sensitive to cytotoxics?
BM cells (+ other rapidly dividing cells) omit the G0 (resting) phase, which is the phase where cytotoxics cannot act
Antimetabolite chemo?
E.g. methotrexate, gemcitabine, fluorouracil, capecitabine
Act at G1 by inhibiting/mimicking DNA bases
Anthracycline chemo
E.g. doxorubicin
Acts at G1 by affecting mitochondrial DNA thus energy generation, and at S phase by inhibiting DNA topoisomerase
Alkylating agents
E.g. cyclophosphamide
Act at S phase by binding DNA helix preventing transcription
Anti-tumour antibiotics
E.g. bleomycin
Act at S phase - break DNA strands
Platinum compounds
E.g. cisplastin
Act at S phase - bind to nucleotide bases = deform double helix
Vinca alkaloids
E.g. vincristine
Act at G2 by inhibiting microtubules and also affect the M phase
Topoisomerase inhbitros
E.g. topotecan
Act at G2 by inhibiting microtubules and also affect the M phase
Taxanes
E.g. docetaxel
Act at G2 by inhibiting microtubules and also affect the M phase
Outline the cell cycle
G0 - resting
G1 - cell growth + preparation for DNA synthesis
G1 checkpoint
S - DNA replication
G2-more growth, prep for mitosis
G2 checkpoint
M - mitosis
What must be taken into account when prescribing cytotoxics?
- Narrow therapeutic indices
- Dose for the individual based on PS, BMI, drug handling ability
- Combination to allow synergism
- Route: IV, PO, SC, intralesional, intrathecal, topical, IM
List the common side effects of chemotherapy
- Head: fatigue, alopecia, ‘chemo brain’
- Skin: plantar palmar erythema, nail ridging as growth stops each cycle, peripheral neuropathy, extravasation
- Lungs: pneumonitis, PE, fibrosis
- Heart: cardiomyopathy (e.g. doxorubicin)
- Blood: myelosuppression, NS, thromboembolism
- Liver: deranged LFTs
- GIT: N+V, mucositis, diarrhoea, constipation
- Renal: AKI, electrolyte imbalance, toxicity
- Bladder: haemorrhagic cystitis
- Repro: impaired fertility, reduced libido, premature menopause, teratogenic
Oral mucositis
Causes difficulty eating + talking, complicated by candida
M: prevention is best like mouth wash after meals/ice cube sucking/carbonated drinks/soft bristle toothbrush, chlorhexidine or saline mouth wash, anaesthetic mouthwash/spray, barrier gels, topical/systemic antifungals if candida
BM suppression
Risk in all cytotoxics except vincristine and bleomycin
Usually peak effect 7-10d after dose
Which agents are most linked to N+V during chemo?
Cisplatin, carboplatin, doxorubicin, daunorubicin, oxalipplatin
When do chemo drugs cause N+V?
In the first 24h acutely, or delayed up to 5d after chemo
Due to stimulation of the CTZ in the area postrema - activates emesis centre in reticular formation
How might N+V be prevented?
Prescribe known antiemetic regiments in preparation - IV pre-treatment, or oral pre-treatment, or daily
Aim at agent with the highest emetogenic potential
Which antiemetics are used for chemo-induced N+V
Ondansetron Dexamethasone Aprepitant Domperidone Metoclopramide
What meds are used for constipation?
- Co-danthramer: stimulant + softener but only in EOLC as poss cardiotoxic
- Glycerine: often as a suppository, local colon irritation to stimulate passage
- Docusate: softener + mild stimulant, draws water into stool
- Lactulose: disaccharide not absorbed from GIT so softens stool by osmosis
- Senna: increases motility + mucous, and reduces fluid absorption
- Movicol: iso-osmotic, adds bulk + increases water absorption + stimulates propulsion + lubrciates
Management of diarrhoea due to chemo
Fluids if dehydrated
Anti-diarrhoeal e.g. loperamide - can prescribe for PRNs but dont use as prophylaxis
May temporarily stop causative agent
Causes + CF of extravasation
Leakage of agent into the tissue around the vein, as cannula doesn’t remain in the vein’s lumen
CF: may have ‘flashback’ but actually a haematoma; pain stinging burning erythema at site of injury (check under clothes as may be away from site of cannula), blistering, change in skin colour
Can lead to severe damage of tendons/nerves/joints/tissues
Not itchy or urticarial - suspect allergy
Management of extravasation
- Stop infusion immediately + disconnect, mark borders of erythema
- DO NOT remove cannula/line
- Aspirate drug from the cannula + some blood if poss
- Cold pack + seek expert advice + implement recommended plan
- Follow up as may evolve over some days
Infusion reactions
Common esp with carboplatin + monoclonal antibodies, so usually give a pre-med to reduce the risk
M-SC atropine
May not necessarily need to avoid in future if reaction was only mild
Non-systemic venous irritation
Due to the drug, other things in preparation, concentration, degradation, too cold (vasospasm if below room temp) and vascular tone
M: stop infusion, warm to encourage vasodilation, flush with a compatible fluid to dilute it, IV steroid, hydrocortisone cream to skin
Late effects of chemotherapy?
Peripheral neuropathy, secondary cancers esp leukaemia, infertility, early menopause, osteoporosis, heart/lung/renal problems, fatigue, mild cognitive impairment
Outline the principles of immunotherapy
Interfere with immune response, most usually immune checkpoint inhibitors which interfere with the relationship between T cells and antigen presenting cells
Interleukins e.g. IL-2 to activate T cell responses
Side effects of immunotherapy
- Any ‘itis’ (excessive immune activity, but usually resolve after stopping or steroids)
- GI like pain, blood in stool, diarrhoea, perforation
- Skin: immune dermatitis, pruritus, dry skin, SJS/TEN
- Hepatic toxicity
- Neuro: GBS, MG (cos immune neuropathies)
- Endocrine effects like hypothyroidism and adrenal insufficiency
Principles of molecular targeted therapies
Patient expresses the targeted molecule AND the drug can interrupt a growth-critical pattern in that cancer
- Monoclonal antibodies (MAB): they bind to a certain antigen blocking downstream signalling thus stopping proliferation. E.g. HER2 inhibitor trastuzumab in breast + some gastric Ca, EGFR inhibitors in bowel cancer (Cetuximab)
- Receptor kinase/small molecule inhibitors (IB): e.g. imatinib (inhibits BCR-ABL fusion in CML)
Side effects of targeted therapies
- Skin: aceniform rash, dryness, hair growth disorder, pruritis, nail changes
- Fatigue
- Myelosuppression
- Diarrhoea, nausea, GI perf
- Arterial thromboembolic events, cardiac ischaemia
- Flu like sx
- Abnormal LFTs
Principles of hormone therapy
Blocking oestrogen in breast + endometrial cancer, e.g. tamoxifen
Blocking androgens in prostate cancer
Minimal toxicity but need to have the detectable cellular receptors
How does radiotherapy work?
High energy ionising radiation damages DNA + causes free radicals which damage proteins/membranes
Is v specific calculation involving lots of planning
Aims of radiotherapy
- radical: usually 4-7w daily treatment in small fields with high total dose. esp for CNS + lymphoma, or as part of adjuvant
- palliative: to alleviate sx like bone mets or RICP or obstructions. Usually 1-10 daily treatments with a larger field of irradiation + low total dose
Early side effects of radiotherapy (d-w)
Erythema, desquamation, fatigue, N+V, alopecia, dysphagia, oral mucositis (esp H+N-often need a PEG), sterility, diarrhoea, low blood counts from going through bone, lymphedema, dysuria, radiation cystitis
Late side effects of radiotherapy (m-y)
Unrelated to acute s/e - due to loss of slowly-proliferating cells causing fibrosis + ischaemia
- Skin: necrosis, pigmentation, telangiectasia, ulceration
- Bone: necrosis, #, impaired growth
- Mouth: ulcers, dryness
- Eyes: cataract, vision loss
- CR: pulmonary/pericardial fibrosis, cardiomyopathy
- Gonads: infertility, menopause
- Bowel: strictures, adhesions, fistulae
- Secondary malignancies: any really, haematological appear earlier
Typical side effects of specific chemotherapy drugs
- Pyrimidine analogues e.g. 5-FU: mucositis, dermatitis
- Platinum analogues e.g. cysplatin: ototoxicity, peripheral neuropathy
- Alkylating agents e.g. haemorrhagic cystitis
- Folic acid antagonists e..g methotrexate: mucositis, liver/lung fibrosis
- Vinca alkaloids e.g. vincristine: neurotoxicity so never give intrathecally; peripheral neuropathy, paralytic ileus
- Bleomycin - lung fibrosis
- Doxorubicin - cardiomyopathy
Types of radiotherapy
- External beam: commonest, like a CT scanner
- Brachytherapy: usually a boost treatment in prostate + cervix, radioactive seeds stay inside and release radiation
- Systemic injected/swallowed (rare)
Radiosensitisers often used when having chemo + radio i.e. chemo that work well with radio, so can have a lower dose of chemo
