Pharmacology: Chemotherapy

Question 1

What is the benefit of biological therapies?

Answer 1

They are rationally designed to target specific molecules whether that be part of the tumour growth pathway or a molecule that is over-expressed etc
They are tumour selective (as opposed to chemo or radio that kills alls cells) so fewer side effects
More efficacious

Question 2

What is imatinib used for?

Is it effective?

Answer 2

Imatinib is a biological therapy initially designed to treat leaukaemia however was found to also be beneficial to GI stromal tumours.
Very efficacious - chances of responding to chemo is 5%, imatinib response rate is 85%.

Question 3

What is the general target for all chemotherapy drugs?

Answer 3

Disrupting DNA replication

Question 4

What phase of the cell cycle do chemotherapies target?

How can this be enhanced?

Answer 4

Chemotherapy can only work in the active stages of the cell cycle (M, G1, S, G2)
Sometimes the cells are in the dormant phase (G0) where they cant be killed, therefore we can give drugs that push these cells into the active cell cycle.

Question 5

Why is chemotherapy given in pulses rather than continuously?

Answer 5

The fractional cell kill hypothesis:
When you administer chemotherapy it kills both bone marrow and cancer cells. The bone marrow cells recover more quickly and therefore you give time for them to recover (but not so much time that the cancer cells recover) before giving the next dose.
Overall there will be a depletion in the number of bone marrow cells but not as much as the cancer cells.

Question 6

Which tumours are highly, moderately and poorly sensitive to chemotherapy?

Answer 6

Highly sensitive: lymphomas, small cell lung, germ cell tumours (chemo may be only treatment needed)
Moderate: breast, colorectal, bladder, ovary, cervix (usually treated with chemo, surgery and radio)
Low: Prostate, renal, brain, endometrial (chemo used as an adjunct)