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CPT > Cancer chemotherapy > Flashcards

Cancer chemotherapy Flashcards

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1
Q

Why is the cell cycle important to consider when giving chemotherapy?

A
  • Chemo agents will only work if the cell is actively going through the cell cycle
  • Cancer drugs won’t work if cell is in the dormant phase
  • Can give drugs to move cells out of dormant phase and into cell cycle - then use chemo drugs
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2
Q

What is the growth fraction of a tumour?

A
  • Proportion of cells dividing at any given time
  • Useful indicator of sensitivity to chemotherapeutic agents
  • Tumours with large growth fractions are more responsive to treatment
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3
Q

Why are multiple cycles of chemotherapy required to eradicate tumours?

A
  • Tumours are heterogenous
  • Different cells in tumours are at different stages of the cell cycle
  • Some cells are proliferating, others are dying or lying dormant
  • Repeated cycles are required to eradicate remaining and regrowing cells
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4
Q

Outline the fractional cell kill hypothesis

A
  • A given dose of chemotherapy kills a constant proportion of a tumour cell
  • Repeated doses are required
  • Frequency and duration of treatment limited by toxicities
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5
Q

Why is chemotherapy given in pulses?

A
  • Allows normal cells to recover in between doses
  • Normal cells recover faster than cancerous cells
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6
Q

What affects the growth fraction of a tumour?

A
  • Dependant on tumour size
  • In early stages when tumour volume is low, growth fraction is high
  • The bigger the tumour, the smaller the growth fraction
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7
Q

What does a small growth fraction mean?

A
  • Less actively dividing cells to be targeted by the chemotherapy
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8
Q

Give some example of highly chemo-sensitive tumours

A
  • Lymphomas
  • Germ cell tumours
  • Small cell lung
  • Neuroblastoma
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9
Q

Give some examples of moderately chemo-sensitive tumours

A
  • Breast cancer
  • Colorectal
  • Bladder
  • Ovary
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10
Q

Give some examples of low chemo-sensitive tumours

A
  • Prostate
  • Renal cell
  • Brain tumours
  • Endometrial cancer
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11
Q

Give some different types of chemo drugs

A
  • Antimetabolites - work on DNA synthesis
  • Alkylating agents - work directly on DNA
  • Intercalating agents - work on DNA transcription
  • Spindle poisons - work on mitosis
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12
Q

Outline the mechanism of action of alkylating agents

A
  • Form inter-strand cross-links between coils of DNA
  • Defective DNA replication
  • Cell death
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13
Q

How do platinum compounds act as anti-cancer drugs?

A
  • Formation of platinated inter and intra-strand adducts - - Leading to inhibition of DNA synthesis
  • DACH platinum adducts are bulky so better DNA synthesis inhibitors
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14
Q

Give an example of an alkylating agent

A
  • Oxaliplatin
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15
Q

Give some examples of antimetabolites

A
  • Methotrexate
  • 5-fluorouracil
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16
Q

What is the mechanism of action of 5-fluorouracil

A
  • Inhibits thymidylate synthase (TS)
  • Pyrimidines can’t be incorporated into final DNA
  • DNA can’t be produced
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17
Q

What is the mechanism of action of methotrexate?

A
  • Inhibits dihydrofolate reductase
  • Prevents purine formation
  • DNA can’t be produced
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18
Q

What is the mechanism of action of spindle poisons?

A
  • Inhibit polymerisation of spindle microtubules
  • Or prevent depolymerisation of microtubule spindles
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19
Q

What are some examples of spindle poisons?

A
  • Taxoids
  • Vinca alkaloids
20
Q

What is the mechanism of action of taxoids?

A
  • Promote assembly of microtubule spindles
  • Prevent disassembly
21
Q

What is the mechanism of action of vinca alkaloids?

A
  • Prevent spindle formation
22
Q

What is the mechanism of resistance of cancer cells against alkylating agents?

A
  1. Decreased entry or increased exit of an agent via a glycoprotein pump that recognises noxious substances
  2. Inactivation of agent in cell by scavenger molecules
  3. Enhanced repair of DNA lesions produced by alkylation
23
Q

What are some side effects of chemotherapy?

A
  • Nausea/vomiting
  • Mucositis
  • Alopecia
  • Skin toxicity
  • Cardio toxicity
  • Lung toxicity
  • Haematological toxcity
24
Q

Why does cancer result in vomiting?

A
  • Multifactorial but includes direct action of chemotherapy drugs on the central chemoreceptor trigger zone
25
Q

Outline the pattern of emesis resulting from chemotherapy

A
  • Acute phase 4-12 hours
  • Delayed onset 2-5 days later
  • Chronic phase may persist up to 14 days
26
Q

Outline alopecia resulting from chemotherapy

A
  • Hair thins at 2-3 weeks
  • May be total loss
  • May regrow during therapy (does not mean that cancer is back)
  • Marked with doxorubicin, vinca alkaloids, cyclophosphamide
  • Minimal with platinums
27
Q

Outline the local skin toxicity caused by chemotherapy

A
  • Irritation and thrombophlebitis of veins
  • Extravasation
  • If a vein gets punctured, drug can enter local tissue
28
Q

Outline the general skin toxicity caused by chemotherapy

A
  • Bleomycin causes hyperkeratosis, hyperpigmentation and ulcerated pressure sores
  • Bulsuphan, doxorubicin, cyclophosphamide, and actinomycin D cause hyperpigmentation
29
Q

Outline mucositis caused by chemotherapy

A
  • GI tract epithelial damage
  • May be profound and involve whole tract
  • Most commonly worst in oropharynx
  • Presents as sore mouth/throat, diarrhoea, GI bleed
30
Q

Which cancer drugs cause cardio-toxicity?

A
  • Cardiomyopathy is caused by doxorubicin and high dose cyclophosphamide
  • Arrhythmias caused by cyclophosphamide and etoposide
31
Q

Which cancer drugs cause lung toxicity?

A
  • Bleomycin
  • Mitomycin C
  • Cyclophosphamide
  • All cause pulmonary fibrosis
32
Q

Outline the haematological toxicity of cancer therapy

A
  • Most frequent dose-limiting toxicity
  • Most frequent cause of death from toxicity
  • Different ages cause variable effects on degree and lineages
  • Neutrophils, platelets, erythrocytes
33
Q

What chemotoxicities are caused by cisplatin and carboplatin?

A
  • Ototoxicity
  • Nephrotoxicity
34
Q

What chemotoxicities are caused by bleomycin?

A
  • Pulmonary fibrosis
35
Q

What chemotoxicities are caused by cyclophosphamide?

A
  • Haemorrhagic cystitis
36
Q

What chemotoxicities are caused by methotrexate?

A
  • Myelosuppression
37
Q

What are the clinical indications of chemotherapy?

A
  • Cancer
  • Different aim in different malignancies
  • Predicted response is also different within the same cancer
  • Balance side effects with anticipated or best outcome
38
Q

What are the routes of chemotherapy administration?

A
  • IV - most common
  • PO - convenient but depends on oral bioavailability
  • SC - convenient in a community setting
  • Intralesional - directly into cancerous area
  • Intrathecal - into CSF by lumbar puncture
  • Topical
39
Q

Through what methods is chemotherapy given to patients IV?

A
  • Bolus
  • Infusional bag
  • Continuous pump infusion e.g. PICC line, Hickman line
40
Q

What causes variability in pharmacokinetics and chemotherapy?

A
  • Abnormalities in absorption
  • Abnormalities in distribution
  • Abnormalities in elimination
  • Abnormalities in protein binding
41
Q

What causes abnormalities in absorption of chemotherapy drugs?

A
  • Nausea and vomiting
  • Compliance
  • Gut problems
42
Q

What causes abnormalities in distribution of chemotherapy drugs?

A
  • Weight loss
  • Reduced body fat
    Ascites
43
Q

What causes abnormalities in elimination of chemotherapy drugs?

A
  • Liver and renal dysfunction
  • Other meds
44
Q

What causes abnormalities in protein binding of chemotherapy drugs?

A
  • Low albumin
  • Other drugs
45
Q

What are the important drug interactions of chemotherapy drugs?

A
  • Other drugs may increase plasma levels of the chemotherapy drug
  • Vincristine and itraconazole (antifungals) lead to more neuropathy
  • Warfarin
  • Methotrexate - caution with prescribing penicillin, NSAIDs
  • Capecitabine, St Johns Wort, grapefruit juice
46
Q

What are the adverse effects of chemotherapy (due to the effect of treatment on the tumour)?

A
  • Acute renal failure - hyperuricaemia caused by rapid tumour lysis leads to precipitation of urate crystals in renal tubules
  • GI perforation at site of tumour
  • Disseminated intravascular coagulopathy
47
Q

What needs to be monitored during chemotherapy?

A
  • Response of the cancer (radiological imaging, tumour marker blood tests, bone marrow/cytogenetics)
  • Drug levels
  • Checks for organ damage (creatinine clearance, echocardiogram)

CPT (22 decks)

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