Principles of chemotherapy Flashcards
What is chemotherapy?
Treatment with drugs that kill cancer cells or make then less active
How do cytotoxic agents work?
Act by interfering with cell division
e.g. by damaging DNA, inhibition of DNA, Inhibition of RNA or protein production or by interfering with microtubule function
How does Herceptin work?
A monoclonal antibody againstbHER2, a growth factor expressed by breast cancer cells
How does Erlotinib work?
A tyrosine kinase inhibitor that blocks Epidermal Growth Factor Receptor (EGFR) – used to treat Non-Small Cell lung cancer
How does Bevacizumab work?
A monoclonal antibody which block Vascular Endothelial Growth Factor (VEGF) receptor – so inhibits angiogenesis
How does Nivolumab work?
A type of immunotherapy used in metastatic melanoma
A monoclonal antibody.
It’s a programmed cell death 1 (PD-1) checkpoint inhibitor. PD-1 pathway may be exploited by tumour cells to escape active T-cell surveillance
Nivolumab can reactivate tumour-specific cytotoxic T-lymphocytes
So re-stimulates anti-tumour immunity
Give examples of cytotoxic agents
5-Fluoro-Uracil (anti-metabolite)
- Acts as a false precursor and blocks the enzyme thymidylate synthase → Inhibits DNA synthesis
Vincristine (tubulin-binding agent)
- Inhibits microtubule assembly & disrupts mitotic spindle formation
Cyclophosphamide (alkylating agent)
- Contain alkyl groups which bind to DNA causing single & double strand breaks and cross-linking between strands
Epirubicin (anthracycline)
- Intercalates between DNA base pairs, forms free radicals
What are the effects of cytotoxic agents on normal organs/tissues?
Most sensitive: ‘renewing’ cells
Eg bone marrow, GI mucosa, hair follicles, spermatogenesis, ovarian follicles
Least sensitive: ‘static’ cells
Eg. neurones, striated muscle
What are the advantages normal cells have over cancerous cells when it comes to cytotoxic agents?
- They have tight control of cell cycle: can be halted to allow for DNA REPAIR
- If cell dies, surviving stem-cells can proliferate to replace the dead cells- only 30% of bone marrow cells are going through the cell cycles at any one time so most cells relatively protected from chemotherapy
What factors can make administration of chemotherapy safe?
- Leave gaps in between doses to allow for normal organs & tissues to recover
Eg. one dose (‘cycle’) every 3 weeks for 6-8 doses - Individualise dose to patient calculated according to body surface area (mg/m2)
- Use drug combinations which don’t have overlapping toxicities i.e. not two which both cause severe bone marrow suppression
What is intra-thecal administration?
The introduction of a therapeutic substance by injection into the subarachnoid space of the spinal cord
What are the common side effects of cytotoxic drugs (chemotherapy)?
Bone marrow suppression
Nausea & Vomiting
Alopecia
Mucositis
Diarrhoea
How are side effects of cytotoxic drugs managed?
Bone marrow suppression
- Blood & Platelet transfusions, GCSF, prompt treatment of infection
Nausea & Vomiting
- Prescribe regular anti-emetics, dexamethasone, metoclopramide, 5HT3 antagonists
Alopecia
- Cold cap, wig
Mucositis
-Mouthwashes, Analgesia
Diarrhoea
-Loperamide, codeine phosphate
What is Doxorubicin?
A type of chemotherapy
What is the risk of secondary malignancy after chemotherapy?
- 1-3% risk of secondary malignancy
- Most common is acute leukaemia, occurring 3-5 years post-treatment
- Most common with ‘alkylating agents’
- Increased risk with multiple drugs, multiple regimens
What are the different indications for chemotherapy?
Radical
- Given with curative intent
Eg. acute leukaemia’s
Adjuvant
- Given to patients at high risk of developing metastatic disease
Eg. post-op chemotherapy in node positive breast cancer
Neo-adjuvant
- Given to shrink tumour volume prior to surgery/radiotherapy
→ operable (e.g. oesophageal cancer)
→ less extensive surgery required (e.g. wide local excision rather than mastectomy)
Palliative
- Given for symptom control
Eg. metastatic breast cancer
How effective is chemotherapy?
- Curable even though widespread
Eg. testicular cancer, some lymphomas & leukaemias - Clear survival benefit, prolong life by some years
Eg. breast, lymphoma, ovarian cancer, colorectal cancer - Modest/equivocal survival benefit, some months at best
Eg. pancreatic, gastric, prostate cancer, high grade gliomas - Chemo-resistant, response rates ~10%,- Eg. melanoma, renal cancer, cholangiocarcinoma
How are patients selected for chemotherapy?
- Patient choice
- Performance status If PS >2 then likely to tolerate poorly co-morbidities, cardiac, renal, liver impairment may need to dose reduce or avoid some drugs
- Treatment intent, if curable then much lower threshold for treatment
What is the RECIST criteria?
Response evaluation criteria in solid tumours
To see if chemotherapy is working
Why might chemotherapy not work?
- Inherent resistance in subpopulation of cells become dominant cell type as more sensitive cells are killed off
Eg. loss of apoptosis due to p53 mutation - Acquired resistance
Eg. production of enzymes which deactivate drug like amplification of mdr-1 gene which encodes a protein which pumps drugs out of cells - Solid tumours have a poor blood supply so there is poor drug delivery and hypoxic cells will be in G0 so less sensitive to chemotherapy
What is Castleman’s disease?
A rare disorder that involves an overgrowth of cells in your body’s lymph nodes
What is a low residue diet?
This is a diet which contains little or no fibre/roughage
The aim of this diet is to reduce the amount of undigested food that passes into the large bowel
Prescribed for patients with GI disorders
What are neurocutaneous disorders?
Disorders that cause growth of tumours in various parts of the body
They present cutaneously with things like cafe al late spots
