Cytotoxic Therapy

Question 1

Cytotoxic drugs can reduce the number of tumour cells but these can increase again between periods of chemo. TRUE/FALSE?

Answer 1

TRUE

Question 2

What are the different phases of the cell cycle that can be interrupted by chemotherapy?

Answer 2

G0 - resting phase
G1 - growing phase
S - DNA synthesis
G2 - proteins from DNA synthesis
M - Mitosis

Question 3

What are the two main types of chemotherapy

Answer 3

Cell Cycle specific
- targets cell cycle
- usually specific to tumour which is rapidly dividing
=> doesn’t kill off as many normal cells

Cell Cycle non-specific

• generally cytotoxic
• kills cells rather than stopping division

Question 4

What types of chemotherapy are cell cycle specific?

Answer 4

Antimetabolites (e.g. methotrexate, hydroxyurea)
- Cant make nucleotides
=> tumour cant make DNA

Mitotic spindle inhibitors (e.g. vincristine, taxotere)

Question 5

What types of chemotherapy are non-cell cycle specific agents?

Answer 5

alkylating agents (e.g. chlorambucil)
- binds to DNA and break strands with free radicals

platinums
- cisplatin/ carboplatin

cytotoxic antibiotics
- anthracyclines
=> impair RNA transcription
=> binds topoisomerase => struggles to unwind and zip to replicate

Question 6

What is the difference in dose and duration between cell cycle and non-cell cycle targeted chemo?

Answer 6

Cell cycle - Duration > dose
- need long duration to continue to remove rapidly dividing cells

Non-cell cycle - Dose > Duration
- High dose to kill off all cells

Question 7

What organs are affected by cell cycle specific chemotherapy?

Answer 7

bone marrow
gut mucosa
hair loss

Question 8

What side effects can be caused by non-cell cycle specific chemo?

Answer 8

• vinca alkaloids cause neuropathy
• anthracyclines - cardiotoxicity
• cis-platinum - nephrotoxic

Question 9

What are the long term side effects of chemotherapy?

Answer 9

alkylating agents - infertility/ secondary malignancy

anthracyclines - cardiomyopathy

Question 10

How are chemo regimens put together to avoid cross reactions and toxicities?

Answer 10

• combination chemo with synergistic mechanisms of action e.g. paclitaxel/ carboplatin
• don’t use drugs in same class

Question 11

When would chemo fail?

Answer 11

• cell cycle specific focus on rapidly dividing cells
  => if the tumour is slow growing chemo may not be as effective
• tumour “sancturies” aka tumour blood barriers, may cause no chemo to get to tumour
• drug resistance may occur

Question 12

What is the drawback of using intense chemo?

Answer 12

causes myelosuppression

Question 13

HOw can intense chemo be used in a safe way to avoid myelosuppression?

Answer 13

• give haematopoietic growth factors (G-CSF)
• combine myelo and non-myelo-suppressive types of chemo
• use stem cell rescue before giving intense chemo drugs

Question 14

What are the potential sources of stem cell transplant?

Answer 14

autologous
allogenic (sibling/unrelated)

Question 15

What chromosomal mutation is present in Chronic Myeloid Leukaemia (CML) and how does this influence treatment?

Answer 15

Philadelphia Chromosome
Translocation 9:22 => affects Tyrosine Kinase Pathway
=> TK Inibitors used to treat