10.2 Chemotherapy

Question 1

What are the classes of Chemotherapy drugs?

Answer 1

Alkylating Agents
Anti-metabolites
Spindle Poisons
Intercalating Agents
DNA Scissors

Question 2

What routes can we take?

Answer 2

Peritoneal
Oral
IV
Intrathecal
Directly into the tumour

Question 3

What are the general ADRs?

Answer 3

Nausea and Vomiting
Fatigue
Bone Marrow Suppression (Infections, Anaemia)
Alopecia
Weight Loss

Question 4

What are some Alkylating Agents?

Answer 4

Cisplatin

Question 5

What are some anti-metabolites?

Answer 5

Methotrexate (6-MP)

5-FU (FDUMP)

Question 6

How do we give doses of chemotherapy?

Why?

Answer 6

Fractionated Doses
Fractional Kill Hypothesis
Let Bone Marrow Recover

Question 7

When do we use chemotherapy?

Answer 7

Neo/Adjuvant
Palliative
With Radiotherapy/Hormonal/Immune Therapy

Question 8

Can Chemo ever cure?

Answer 8

Yes, Blood borne tumours, Soft tissue

Not on it’s own for solid tumours

Question 9

What are some Spindle Poisons?

Answer 9

Vinca Alkyloids

Taxanes

Question 10

What are some DNA Scissors?

Answer 10

Bleomycin

Question 11

What are some Intercalating Agents?

Answer 11

Anthracyclins

Question 12

What are the three types of cancer cell?

Which are succeptable to chemotherapy

Answer 12

A -Cells which are dividing and contribute to tumour growth. Succeptable to Chemo
Cells which are dormant in G0 but can become A if conditions change. Not succeptable
C- Cannot divide, add to the tumour bulk

Question 13

How do alkylating agents work?

Answer 13

They form bulky adducts by binding to DNA strands (inter/intrastrand)
Prevent DNA unwinding so no DNA replication

Question 14

How do intercalating agents work?

Answer 14

They get between base pairs and prevent replication

Prevent Topoisomerase II

Question 15

How do anti-metabolites work?

Answer 15

They work best in S1 (rapidly diving cells)
They prevent base synthesis
so DNA/RNA/Protein synthesis cannot occur
Causes apoptosis

Question 16

How do spindle poisons work?

Answer 16

Prevent successful Mitosis
VA prevent spindle formation from tubules
Taxanes prevent spindles from breaking down into microfilaments
They cause DNA to be in one cell, or cells don’t seperate therefore causes apoptosis

Question 17

How do DNA Scissors work?

Answer 17

Bind to DNA/Chelates/Fe2+
Form Free Radicals
They cut strands of DNA

Question 18

When do DNA Scissors work best?

Answer 18

G2

Question 19

Which types of cancers do anti-metabolites not work as well in

Answer 19

Slow Growing Tumours

Dormant/Latent Tumours

Question 20

When do Spindle Poisons act? (In the Cell Cycle)

Answer 20

M Phase

Question 21

How do you work out dosage?

Answer 21

Work out the Body Surface Area

Renal and Plasma levels are taken into account as well

Question 22

When do Alkylating Agents have the most effect?

In the Cell Cycle…

Answer 22

S Phase

Question 23

How is the PK of Chemotherapy agents effected?

Answer 23

Distribution: Age, Weight, Sex, Vomiting, GI problems (Oedema)
Elimination: Renal/Liver Failure
Other medication

Question 24

Why are oral agents not as good?

Answer 24

Side Effects - Vomiting
Toxic
Very Variable Bioavailability

Question 25

What are some DDIs of Vincristine?

Answer 25

Antifungals, increases neuropathy

Question 26

What are some DDIs of 5FU

Answer 26

Warfarin, increases bleeding risk

Question 27

What are some DDIs of Methotrexate

Answer 27

Penicillin, NSAIDs

Question 28

What are some DDIs of Capacitabine?

Answer 28

St Johns Wort

Question 29

What are some severe ADRs?

Answer 29

Neutropenic Sepsis
Acute Renal failure (tumour lysis --> hyperuricaemia)
GI perforation
Lung Fibrosis (Bleomycin)
Arrhythmias

Question 30

How do you monitor Chemotherapy?

Answer 30

Cancer Response - Imaging, Tumour Markers
Drug Level - monitor plasma concentration
Organ Damage - ECG, Creatinine Clearance