Chemotherapy

Question 1

What is the fractional cell kill hypothesis?

Answer 1

The reason we give chemotherapy in doses and not as a continuous treatment is because it kills any rapidly dividing cell.
So by giving doses you leave time for cells like bone marrow to divide some more and regain numbers before attacking again.
By doing this you should kill of tumour cells more than normal cells over time

Question 2

What are the different sites of cytotoxic action a chemotherapy drug can work at?

Answer 2

DNA synthesis - Antimetabolites
DNA itself - Alkylating agents
DNA transcription and duplication - Intercalating agents
Mitosis - Spindle poisons

Question 3

How do alkylating agents work?

Answer 3

Cisplatin (platinum)
Compounds (platinum normally) form inter and intra strand adducts between DNA bases, this stops the DNA from being able to unzip to replicate

Question 4

How do antimetabolites work?

Answer 4

Methotrexate and 5-Fluorouracil (6-Mercaptopurine)

Inhibit enzymes in the folate cycle preventing DNA being created

Question 5

How do spindle poisons work?

Answer 5

Vinca alkaloids (Vincristine, Vinblastine)
Taxanes (Paclitaxel)
These inhibit polymerization of microtubules
Polymerization of the microtubules is required to form spindle fibres

Question 6

What mechanisms of resistance can occur against alkylating agents?

Answer 6

Decreased entry or increase exit of agent (into cell)
Inactivation of agent in cell
Enhanced repair of DNA lesions produced by alkylation

Question 7

What are the clinical indications of chemotherapy?

Answer 7

Cancer

Aim is different in different malignancies though

Side effects vs anticipated or best outcome

Question 8

What are the side effects of chemotherapy?

Answer 8

Alopecia
Mucositis
Pulmonary fibrosis
Nausea/vomiting
Cardiotoxicity
Diarrhoea
Local reaction
Cystitis
Renal failure
Sterility
Myalgia
Myelosuppression
Neuropathy
Phlebitis

Question 9

What are some of the adverse effects of chemotherapy due to the effect of treatment o the tumour?

Answer 9

Acute renal failure - often multifactorial
- Hyperuricaemia caused by rapid tumour lysis leads to
precipitation of urate crystals in renal tubules

GI perforation at site of tumour - reported in lymphoma

Disseminated intravascular coagulopathy
- e.g. onset within a few hours of starting treatment for
acute myeloid leukaemia

Question 10

Tell me about skin toxicity in chemotherapy.

Answer 10

Local

• Irritation and thrombophlebitis of veins
• Extravasation

General

• Bleomycin
  
  • Hyperkeratosis
  • Hyperpigmentation
  • Ulcerated pressure sores

Question 11

What are the cardiotoxicity risks of chemotherapy?

Answer 11

Cardio-myopathy

• Doxorubicin ++
• High dose cyclophosphamide
• Mortality approx. 50%

Arrhythmias

• Cyclophosphamide
• Etoposide

Question 12

How do you monitor chemotherapy?

Answer 12

Response of the cancer

• Radiological imaging
• Tumour marker blood tests
• Bone marrow/cytogenetics

Drug levels
- E.g. Methotrexate drug assays taken on serial days to ensure clearance from the blood after folinic acid rescue

Checks for organ damage

• Creatinine clearance
• Echocardiogram