Chemotherapy

Question 1

What process does chemotherapy target in cells

Answer 1

Chemotherapy targets the cell cycle and does not work if they cell goes into G0

Question 2

How should chemotherapy agents be given and why

Answer 2

Chemotherapy should be given in pulsatile doses with enough time between each dose for bone marrow cells to recover

Tumour cells do not recover as quickly as bone marrow cells so their level will decrease over time

Question 3

What are the types of chemotherapy agents

Answer 3

Anti-metabolites

Alkylating agents

Intercalating agents

Spindle poisons

Question 4

How do antimetabolites work and give some examples

Answer 4

Antimetabolites inhibit DNA synthesis

5-furouracil - inhibits thymidylate synthase to inhibit dTMP production

Methotrexate - inhibits folate cycle to inhibit production of dTMP by decreasing products of the cycle

Question 5

Describe how alkylating agents work as a chemotherapy agent

Answer 5

Alkylating agents form bonds between two strands of DNA to prevent replication

May cause strand break or double strand break to stimulate cell death

Some tumour cells have alkylating agent pumps to pump out the drug and prevent its function

Question 6

How do intercalating agents act as a chemotherapy agent

Answer 6

Intercalating agents affect DNA transcription and duplication

Question 7

How do spindle poisons act as chemotherapy agents

Answer 7

Spindle poisons inhibit mitosis by preventing spindle formation or function

Microtubule-binding agents distrup microtubule dynamics by either inhibiting polymerisation or by stimulating polymerisation and preventing depolymerisation (spindles become rigid so do not function)

Question 8

Name some side effects of chemotherapy

Answer 8

Mucositis - ulcers of mouth which can spread thoughout GI tract

Alopecia - esp with doxorubicin, vina alkaloids, cyclophosphamide

Nausea and vomiting - stimulation of CTZ

Cystitis

Sterility

Myalgia

Neuropathy

Pulmonary fibrosis - esp with bleomycin, mitomycin C, cyclophosphamide, melphalan, chlorambucil. Gets worse if given oxygen

Cardio-toxicity - cardio-myopathy and arrhythmias

Local reaction

Skin toxicity - hyperpigmentation, hyperkeratosis, pressure sores, Beau’s lines, hand-foot syndrome

Renal failure - often multifactoral. Hyperuricaemia can cause renal failure if there is rapid tumour lysis - precipitation of urate crystals in renal tubules -> renal failure

Myelosuppression

Phlebitis

DIC

Question 9

What patient factors affect the dosing of chemotherapy agents

Answer 9

Surface area and/or BMI
Drug handling ability

Generaly wellbeing

Question 10

Name some DDIs in chemotherapy

Answer 10

Vincristine and itraconazole - increased neuropathy

Capecitabine and warfarin

Methotrexate and penicilin/NSAIDs

Capecitabine and St John’’s Wort or grapefruit juice