CPT20 - Cancer Chemotherapy

Question 1

What is the fractional cell kill hypothesis?

Answer 1

One dose of chemotherapy will kill a constant fraction of the cells in a population (healthy and cancerous)

The next dose is given when the bone marrow cells reach high levels again

The bone marrow cells recover faster than the cancer cells

Question 2

4 types of cytotoxic agents

Antimetabolites x2
Alkylating Agents (+4 mechanisms of resistance)
Intercalating Agents
Spindle Poisons x2

Answer 2

1. ) Antimetabolites - e.g. methotrexate, 5-Fluorouracil
   - inhibits enzymes in the folate cycle, preventing the formation of THF which is needed to make purine (AA)
   - 5-Fluorouracil ↓thymidylate synthase –> ↓DHF
   - methotrexate ↓dihydrofolate reductase –> ↓THF
2. ) Alkylating Agents - e.g. oxaliplatin
   - inter/intrastrand platinum-DNA crosslinks
   - inhibits DNA replication and transcription
   - resistance: ↓entry, ↑exit, inactivation, ↑repair
3. ) Intercalating Agents - e.g. doxorubicin
   - damages DNA, preventing DNA replication
4. ) Spindle Poisons - microtubule-binding agents
   - taxoids: prevents depolymerisation of microtubules so chromatids cannot separate during anaphase
   - vinca alkaloids: prevents formation of the spindle fibres in the first place (inhibits polymerisation)

Question 3

Common side effects of chemotherapy

Vomiting
Alopecia
Skin Toxicity
Haematological Toxicity
Others x6

Answer 3

1. ) Vomiting - chemotherapy drugs act in the CTZ
   - can be acute (4-12hrs), delayed (2-5d), chronic (>14d)
2. ) Alopecia - hair thins at 2-3 weeks
   - worse with doxorubicin, vinka alkaloids, cyclophosphamide, minimal with antimetabolites
   - can be helped with scalp cooling
3. ) Skin Toxicity - can be local or general
   - local: thrombophlebitits, extravasation
   - general: hyperpigmentation, hyperkeratosis, ulcerated pressure sores
4. ) Haematological Toxicity - often affected by dose
   - most frequent cause of death from toxicity
   - variable effects from different agents
5. ) Others - heart, lungs, GI tract, kidneys
   - cardiomyopathy, arrhythmias, pulmonary fibrosis, mucositis, diarrhoea, acute renal failure