cytotoxic drugs

Question 1

how chemo + radio works

Answer 1

damages DNA of cancer cells as it divides (mitosis)
- cell recognises it i damaged beyond repair + dies by process of apoptosis

often involves protein in cell nucleus - p53
-> mutation in p53 makes it more difficult to treat with chemo + radio

Question 2

why does chemo fail?

Answer 2

Slow tumour doubling time
Tumour “sanctuaries”

Drug resistance mechanisms
o Decreased drug accumulation – MDR/PGP
o Altered drug (por-drug) metabolism – cyclophosphaminde
o Increased DNA repair, cis-platinum resistance
o Altered gene expression – reduced topoisomerase II

Question 3

intensifying chemo

Answer 3

Limited by myelosuppression
Overcome by –
o Use haematopoietic growth factors
o Combine myelosuppressive/non-myelosuppressive agents
o Intensify doses of active drugs (log-linear tumour kill) + stem (progenitor) cell rescure

Question 4

is are PET scans used to improve how chemo is given in Hodgkins lymphoma

Answer 4

Hodgkin’s after 2 out of 6 course of ABVD -> risk adapted therapy
- If PET scan reduced
o Very likely to be cured
o Avoid side effects by missing out bleomycin in cycles 3-6
- If PET still positive
o Very high chance of relapse
o Escalate treatment to escBEACOPP despite more toxicity

Question 5

monoclonal antibodies

Answer 5

• Immune treatment
• Affects only cells which posses target protein
• Avoid side effects
• Unfortunately most are currently used in combination with chemo rather than instead of so same risks
• More effective than chemo alone

Rituximab
o Improves responses + cures in patients with high grade B cell NHL
o Maintenance rituximab prolongs survival + time to next treatment in low grade + mantle cell NHL
o Now given as 5 minute injection under skin rather than IV infusion to save time

Question 6

immune therapy

Answer 6

= allogenic bone marrow transplant (from matched donor

Tcells from donor cause immune attack on cancer
- but also may attack normal cells, very toxic, graft vs host

Question 7

neutropenic sepsis

Answer 7

Neutrophil count of 0.5*109 in patients whos having anticancer treatment + has one of the following
o Temp >38
o Other signs/symptoms consistent with clinically significant sepsis

common complication of cancer
usually 7-15days post chemo

Question 8

commonest cause of neutropenic sepsis

Answer 8

staphylococcu epidermidis / staph aureus

Question 9

what type of causative bacteria is lifethreatening in neutropenic sepsis

Answer 9

GRAM NEGATIVE
- empirical treatment with broad spectrum antibiotics esp covering gram neg as soon as neutropenic fever

Question 10

what can prolonged neutropenia make patients suceptible to

Answer 10

fungal infection
- unresponsive to antibacterial agents

Question 11

neutropenic sepsis prophylaxis

Answer 11

fluoroquinolone - levofloxacin, ciprofloxacin

Question 12

management of neutropenic sepsis

Answer 12

-Start antibiotics immediately, do not wait for WBC
o Empirical antiobiotic therapy with PIPERACILLIN WITH TAZOBACTAM (TAZOCIN)
o Always take blood cultures before giving antibiotics but do not wait for full infection screen to be preformed

• Platelet transfusion
• +/- red cell transfusion (irradiated red cells)

If not responding after 4-6days - investigate for fungal