Principles of cancer therapy

Question 1

What is the role of the cancer MDT?

Answer 1

Standardise
Continuity 
Reduce delays
Communication
Recruitment to clinical trials
Education

Question 2

Neoadjuvant meaning

Answer 2

Chemo/radio given before definitive surgery/radio to optimise outcomes

Question 3

Adjuvant meaning

Answer 3

Treatment after definitive surgery/radio to reduce recurrence

Question 4

Maintenance treatment

Answer 4

Maintain remission or slow growth after initial treatment

Question 5

Curative treatment

Answer 5

Aims for no detectable cancer after treatment

Usually means a systemic treatment because of micro-mets

Question 6

Palliative treatment

Answer 6

To relieve sx + improve QoL, can affect prognosis but not lead to cure

Question 7

Performance status

Answer 7

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

Question 8

How can cancer cells acquire resistance to chemo?

Answer 8

• Efflux pumps
• Reduced drug uptake
• Increased drug metabolism
• Alteration of cell cycle checkpoints
• Impaired apoptosis
• Altered drug target morphology

Question 9

How do they try to prevent chemo resistance?

Answer 9

• Combination of drugs based on action + not overlapping toxicities
• Some toxicity permissible as need maintained doses when cure realistic

Question 10

Why are bone marrow cells very sensitive to cytotoxics?

Answer 10

BM cells (+ other rapidly dividing cells) omit the G0 (resting) phase, which is the phase where cytotoxics cannot act

Question 11

Antimetabolite chemo?

Answer 11

E.g. methotrexate, gemcitabine, fluorouracil, capecitabine

Act at G1 by inhibiting/mimicking DNA bases

Question 12

Anthracycline chemo

Answer 12

E.g. doxorubicin

Acts at G1 by affecting mitochondrial DNA thus energy generation, and at S phase by inhibiting DNA topoisomerase

Question 13

Alkylating agents

Answer 13

E.g. cyclophosphamide

Act at S phase by binding DNA helix preventing transcription

Question 14

Anti-tumour antibiotics

Answer 14

E.g. bleomycin

Act at S phase - break DNA strands

Question 15

Platinum compounds

Answer 15

E.g. cisplastin

Act at S phase - bind to nucleotide bases = deform double helix

Question 16

Vinca alkaloids

Answer 16

E.g. vincristine

Act at G2 by inhibiting microtubules and also affect the M phase

Question 17

Topoisomerase inhbitros

Answer 17

E.g. topotecan

Act at G2 by inhibiting microtubules and also affect the M phase

Question 18

Taxanes

Answer 18

E.g. docetaxel

Act at G2 by inhibiting microtubules and also affect the M phase

Question 19

Outline the cell cycle

Answer 19

G0 - resting

G1 - cell growth + preparation for DNA synthesis

G1 checkpoint

S - DNA replication

G2-more growth, prep for mitosis

G2 checkpoint

M - mitosis

Question 20

What must be taken into account when prescribing cytotoxics?

Answer 20

• 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

Question 21

List the common side effects of chemotherapy

Answer 21

• 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

Question 22

Oral mucositis

Answer 22

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

Question 23

BM suppression

Answer 23

Risk in all cytotoxics except vincristine and bleomycin

Usually peak effect 7-10d after dose

Question 24

Which agents are most linked to N+V during chemo?

Answer 24

Cisplatin, carboplatin, doxorubicin, daunorubicin, oxalipplatin

Question 25

When do chemo drugs cause N+V?

Answer 25

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

Question 26

How might N+V be prevented?

Answer 26

Prescribe known antiemetic regiments in preparation - IV pre-treatment, or oral pre-treatment, or daily Aim at agent with the highest emetogenic potential

Question 27

Which antiemetics are used for chemo-induced N+V

Answer 27

``` Ondansetron Dexamethasone Aprepitant Domperidone Metoclopramide ```

Question 28

What meds are used for constipation?

Answer 28

* 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

Question 29

Management of diarrhoea due to chemo

Answer 29

Fluids if dehydrated Anti-diarrhoeal e.g. loperamide - can prescribe for PRNs but dont use as prophylaxis May temporarily stop causative agent

Question 30

Causes + CF of extravasation

Answer 30

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

Question 31

Management of extravasation

Answer 31

* 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

Question 32

Infusion reactions

Answer 32

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

Question 33

Non-systemic venous irritation

Answer 33

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

Question 34

Late effects of chemotherapy?

Answer 34

Peripheral neuropathy, secondary cancers esp leukaemia, infertility, early menopause, osteoporosis, heart/lung/renal problems, fatigue, mild cognitive impairment

Question 35

Outline the principles of immunotherapy

Answer 35

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

Question 36

Side effects of immunotherapy

Answer 36

* 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

Question 37

Principles of molecular targeted therapies

Answer 37

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)

Question 38

Side effects of targeted therapies

Answer 38

* 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

Question 39

Principles of hormone therapy

Answer 39

Blocking oestrogen in breast + endometrial cancer, e.g. tamoxifen Blocking androgens in prostate cancer Minimal toxicity but need to have the detectable cellular receptors

Question 40

How does radiotherapy work?

Answer 40

High energy ionising radiation damages DNA + causes free radicals which damage proteins/membranes Is v specific calculation involving lots of planning

Question 41

Aims of radiotherapy

Answer 41

* 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

Question 42

Early side effects of radiotherapy (d-w)

Answer 42

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

Question 43

Late side effects of radiotherapy (m-y)

Answer 43

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

Question 44

Typical side effects of specific chemotherapy drugs

Answer 44

* 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

Question 45

Types of radiotherapy

Answer 45

* 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