Chemotherapy IA %% +-+

Question 1

How do you deliver systemic therapy?

Answer 1

• Oral or intravenous route
• Regular cycles with timing dependent on the findings from pharmacokinetics (half life, excretion)
• May be need for delay if toxicities develop
• Intensification previously evaluated: better in non-solid tumours

Question 2

Methods of assessing drug activity

Answer 2

1. Objective response in advanced disease via CT scan, PET scan and/or clinical examination; RECIST criteria if radiological
2. Improved

• overall survival (OS)
• progression-free survival (PFS)
• improved quality of life (QoL)

3. ADJUVANT treatment improves survival. Meaning: applied after initial treatment for cancer, especially to suppress secondary tumour formation.
4. NEOADJUVANT may improve survival through increasing operability or reduce the ‘field size’ of radical radiotherapy. Meaning: treatment given as a 1st step to shrink a tumor before the main treatment, which is usually surgery, is given.

Question 3

Mitosis stages pic

Answer 3

Question 4

Site of action of cytotoxic agents pic

Answer 4

• Antimetabolites ⇒ DNA synthesis
• Alkylating agents ⇒ DNA
• Intercalating agents ⇒ DNA transcripition & duplication
• Spindle poison ⇒ Mitosis

Question 5

Alkylating agents

Answer 5

• alkyl group allows covalent bonds with other molecules
• DNA helix X-links intra- and interstrand
• attach to free guanines at N6 on separated DNA strands
• can not act as templates for new DNA formation

Question 6

Alkylating agents pic

Answer 6

Question 7

Antimetabolites

Answer 7

• similar chemical structure to essential metabolites required by cell prior to cell division
• may be incorporated into new nuclear material or bind irreversibly with vital enzymes to inhibit cell division
• eg. antagonise folic acid (methotrexate), antagonise purine (6-mercaptopurine, 6-thioguanine), inhibit thymidylate synthase (5-fluorouracil), incorporate fluoridated nucleoside in place of normal nucleoside (%FU instead of uracil in RNA)

Question 8

Vinca alkaloids & Taxanes

Answer 8

Vinca alkaloids

• metaphase arrest agents; bind to tubuli and block microtubule formation and spindle formation (essential for metaphase of mitosis)

Taxanes

• promote spindles and ‘freeze’ cells at that stage of cycles

Question 9

Antimitotic antibiotics

Answer 9

Anthracyclines and Non-anthracyclines

• intercalate (instert inbetween) and inhibit DNA and RNA synthesis
• membrane binding and increase permeability to various ions
• free radicals disrupt DNA chain and prevent mitosis
• metal ion chelation resulting in cytotoxic compounds
• alylation blocking DNA replication

Question 10

Overall sites cell cycle pic

Answer 10

Question 11

Combination therapy

Answer 11

Combine those with

Different mechanism of action

• Synergistic or at least additive
• Reduce risk of developing resistance

Dissimilar toxicity profile eg not both with neurotoxicity (cisplatin and taxane)

• Give each to maximum tolerated dose

Question 12

Complex site of action pic

Answer 12

Question 13

Side effects of chemotherapy pic

Answer 13

Question 14

Mechanisms of CINV

Answer 14

Question 15

Other systemic

Answer 15

Hormonal drugs

• Anti-oestrogen Tamoxifen, aromatase inhibitors for breast cancer
• Gonadorelin analogue eg Goseralin (Zoladex)
• Anti-androgen (CPA, flutamide) for prostate cancer

Targeted drugs against

• Epidermal growth factor receptor (EGFR) Gefitinib/Erlotinib
• Vascular endothelial receptor (VEGF) Bevacizumab (Avastin)
• Multiple targets sorafenib, sunitinib, etc

Question 16

Immunotherapy

Answer 16

• Combinations of Ipi and Nivo approved in melanoma
• Side-effects are immune-mediated eg colitis, pneumonitis, endocrinopathies, etc