Chemotherapy IA %% +-+ Flashcards Preview

ME2308 Principles of Disease > Chemotherapy IA %% +-+ > Flashcards

Flashcards in Chemotherapy IA %% +-+ Deck (16)
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1

How do you deliver systemic therapy?

  • 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

2

Methods of assessing drug activity

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. 

3

Mitosis stages pic 

4

Site of action of cytotoxic agents pic

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

5

Alkylating agents

  • 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

6

Alkylating agents pic

7

Antimetabolites

  • 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)

8

Vinca alkaloids & Taxanes

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

 

9

Antimitotic antibiotics

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

10

Overall sites cell cycle pic 

11

Combination therapy

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

12

Complex site of action pic

13

Side effects of chemotherapy pic 

14

Mechanisms of CINV

15

Other systemic 

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

 

16

Immunotherapy

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