Which types of tumour are highly sensitive to chemotherapy
Lymphomas Germ cell tumours Small cell lung Neuroblastoma Wilm’s tumour
Which types of tumour are moderately sensitive to chemotherapy?
Breast Colorectal Bladder Ovary Cervix
Which types of tumour have low sensitivity to chemotherapy?
Prostate
Renal cell
Brain tumours
Endometrial
What are the roles of chemotherapy?
Curative or palliative
Adjunct to surgery/radiotherapy or given in isolation
Aims to kill/prevent replication of tumour cells
Why is chemotherapy usually administered IV rather than orally?
Oral delivery would damage the GI tract and IV administration allows fine control/titration of dose.
What are the four groups of chemotherapy?
Antimetabolites
Alkylating/Platinating agents
Antibiotics
Microtubule inhibitors
Give examples of antimetabolites.
Capecitabine
5-Fluorouracil (5-FU)
6-Mercaptopurine
Give examples of alkylating/platinating agents.
Nitrogen mustards - Cyclophosphamide, Chlorambucil (alkylating)
Cisplatin (platinating)
Give examples of antibiotics used in chemotherapy.
Bleomycin
Epirubicin/doxarubicin
Give examples of microtubule inhibitors.
Vinca alkaloids - vincristine
Taxanes
What are the common side effects of chemotherapy?
Fatigue Nausea and vomiting Alopecia Altered bowel habit Altered taste Mucositis Easy bruising/bleeding - thrombocytopenia Increased infection risk - neutropenia Acute renal failure (drug cleared renally)
What is the mechanism of action of alkylating/platinating agents?
Target DNA synthesis in G1/S phase.
Form a covalent bond with DNA nucleosides disrupting structure and therefore preventing replication.
(Agents form positive ion which act as an electrophile, form covalent bond with DNA nucleosides)
What specific ADRs are caused by alkylating and platinating agents?
Peripheral, sensory and motor neuropathy
High frequency ototoxicity
What is the mechanism of action of mitotic spindle inhibitors?
Target tubules proteins in the mitotic phase
Chromosomes cant align and separate into two daughter cells correctly
(Vinca alkaloids inhibit polymerisation of tubulin so microtubules can’t form whereas Taxanes bind irreversibly to tubulin and stabilises the microtubules so it can’t separate)
What specific ADRs are caused by mitotic spindle inhibitors?
Neurotoxicity - glove and stocking peripheral neuropathy
What are the two groups of antibiotics used in chemotherapy?
Glycopeptide antibiotics - e.g. bleomycin
Anthracycline antibiotics - e.g. doxorubicin
What is the mechanism of action of glycopeptide antibiotics (bleomycin)?
Forms free radicals when cheated with Fe2+ ions which attack phosphodiester bonds in DNA - results in cutting of DNA strands.
Most effective in G2 stage.
What specific ADRs are caused by bleomycin?
Pulmonary fibrosis (10%)
What is the mechanism of action of anthracycline antibiotics (doxorubicin)?
Targets DNA synthesis in S phase.
Intercalate between the base pairs in DNA which interferes with transcription/replication.
Topoisomerase II inhibition.
Also generate free radicals - damage DNA
What specific ADR is associated with doxorubicin?
Cardiotoxic
What is tamoxifen?
A selective oestrogen receptor modulator (SERM)
Acts as an antagonist of the oestrogen receptor in breast tissue
What is the mechanism of action of tamoxifen?
Tamoxifen is metabolised in the liver to its active form, competitively binds to oestrogen receptors.
Causes cells to remain in the G0 and G1 phase of cell cycle.
Why can’t all breast cancers be treated using tamoxifen?
The breast cancer must be oestrogen receptor (ER) positive
What are the side effects of tamoxifen?
Hot flushes/sweats
Increased DVT/PE risk
Weight gain
Increased risk of endometrial cancer
How can chemotherapy be monitored during treatment?
Response of cancer:
- radiological imaging
- tumour marker blood tests
- bone marrow/cytogenetic
Drug levels
Checks for organ damage:
- creatinine clearance
- echocardiogram
What is the difference between neoadjuvant and adjuvant chemotherapy?
Neoadjuvant - given before surgery or radiotherapy in order to shrink tumour
Adjuvant - given after surgery in order to reduce risk of relapse