Chemotherapy Flashcards
What are the three compartments cells occupy in a solid tumour?
A - dividing cells
B - resting cells capable of dividing
C - cells no longer divide but contribute to tumour volume
What are the three objectives of cancer therapy?
Curing patient
Prolonging life
Palliative therapy
Which cells are the only ones susceptible to most cytotoxic drugs?
Compartment A
What is the aim of chemotherapy?
To kill all malignant cells in the body
Give 8 toxic effects of chemotherapy
Bone marrow suppression Impaired wound healing Loss of hair Damage to GI epithelium Growth stunted Reproductive system - sterility Teratogenicity - effect development of foetus Nausea and vomiting
What are two possible targets for anti cancer drugs?
Hormonal regulation of tumour growth
Defective cell cycle controls
What are the four classes of anti cancer drugs?
Cytotoxic
Hormones
Monoclonal antibodies
Protein kinase inhibitors
What do alkylating agents target?
Cells in S phase
How do alkylating agents work?
Form covalent bonds with DNA, prevent uncoiling, inhibits replication.
What are the side effects with prolonged use of alkylating agents?
Sterility (esp men), increased risk of non lymphocytic leukaemia.
What are the 4 classes of alkylating agents?
Nitrogen mustards
Nitrosoureas
Platinum compounds
Others
What is the name of the first anti cancer drug?
Mechlorethamine
How are nitrogen mustards given and why?
IV - very reactive
Give 5 examples of nitrogen mustards?
Cyclophosphamide, melphalan, chlorambucil, bendamustine, estramustine.
How is cyclophosphamide administered and activated?
Orally, activated by liver.
What is estramustine reliant on?
Testosterone
What can nitrosoureas do?
Cross blood brain barrier - highly lipophilic. Treatment for CNS tumours.
Name 2 nitrosoureas and how they would be administered.
Carmustine (BCNU) IV
Lomustine (CC NU) given orally
What type of drug is cisplatin?
Platinum compound
Is cisplatin potent?
Yes
How does cisplatin work?
Binds to RNA Increase DNA and protein, binds to purine bases.
What may develop when using cisplatin?
Resistance
Which cancers are more sensitive to cisplatin?
Testicular/ovarian cancer
How is cisplatin given?
Slow IV injection/infusion
What are the side effects of cisplatin?
Very nephrotoxic
Severe nausea/vomiting
Risk of tinnitus, peripheral neuropathy, hyperuricemia (gout) and anaphylaxis
What other platinum compound is derived from cisplatin but gives less side effects and can be given as an outpatient?
Carboplatin
What is the problem with carboplatin?
More myelotoxic - damages bone marrow
Which platinum compound is used to treat colorectal cancer with fluorouracil and folinic acid?
Oxaliplatin
What is busulfan?
A leukaemia treatment selective for bone marrow alkylating agent.
What is procarbazine?
A alkylating agent used to treat Hodgkin’s disease
What is a side effect of procarbazine?
Can cause hypersensitivity rash and inhibits MAO as enzyme breaks down noradrenaline and dopamine.
What is trabectedin?
Alkylating agent used to treat soft tissue sarcoma and advanced ovarian cancer
What is a side effect of trabectedin?
Hepatotoxic
How do antimetabolites work?
Folate antagonists - cells cannot divide/no DNA synthesis.
Which antimetabolite inhibits dihydrofolate reductase?
Methotrexate
How would you give methotrexate?
Orally, IM, IV or intrathecally.
Does methotrexate cross the bbb?
No
Who should have a lower dose of methotrexate?
Renal impairment
Whichever drugs can reduce the excretion and thus increase toxicity of methotrexate
?
NSAID’s
What is methotrexate given with in high doses to rescue normal cells?
Folinic acid
What other condition is methotrexate used in to suppress the immune system?
Rheumatoid arthritis
What do pyrimidine analogues compete with?
C and T bases
What do pyrimidine analogues inhibit?
DNA synthesis
List 4 pyrimidine analogues
Fluorouracil, capecitabine, cytarabine and gemcitabine
How are pyrimidine analogues given?
Parenterally
What do purine analogues compete with?
A and G bases
What do purine analogues inhibit?
Purine metabolism
Give 3 examples of purine analogues
Mercaptopurine/tioguanine, pentostatin and fludarabine.
Mercaptopurine/tioguanine is mainly used for what treatment?
Leukaemia treatment
What is doxorubicin and how does if work?
Cytotoxic antibiotic, binds to DNA and inhibits DNA/RNA synthesis. Inhibits topoisomerase 2
How is doxorubicin given?
By IV infusion
What are the problems with doxorubicin?
Dissolves the tissues of the skin.
Can cause dysrhythmias/heart failure in high doses.
What is bleomycin?
Cytotoxic antibiotic
How does bleomycin work?
Degrades pre formed DNA. Active against non-dividing cells.
What are the bad effects of bleomycin?
Causes pulmonary fibrosis in 10% patients. 50% patients develop mucocutaneous reactions such as mouth sores, hair loss, fungal infections and hyperpyrexia.
Which cytotoxic antibiotic is used in the treatment of paediatric cancers?
Dactinomycin
Vinka alkoids are a type of what?
Plant derivative
Give 3 examples of vinka alkoids?
Vincristine, vinblastine, vindesine
What are vinka alkoids derived from?
Madagascar periwinkle
What do vinka alkaloids prevent?
•Prevent polymerisation of tubulin → microtubules → prevents spindle formation
When can the effects of vinka alkaloids occor?
Only during mitosis M phase
Vinka alkaloids are relatively non toxic except for?
Vincristine - neuromuscular effects
Give two examples of taxanes
•E.g. paclitaxel, docetaxel
paclitaxel, docetaxel are derived from what and used to treat what?
Yew tree.
Breast cancer.
paclitaxel/ carboplatin are used to treat…
Ovarian cancer
Etoposide is derived from what?
The mandrake root
Etoposide is used to treat what?
Testicular cancer/lymphomas
Etoposide must avoid what?
Skin contact
What can Etoposide cause?
A rapid fall in blood during IV Infusion
Which cancers are hormones used to treat?
•Used in treatment of cancers in hormone-sensitive tissues (e.g. breast, prostate, ovaries)
How do hormones work?
Tumour growth inhibited by R antagonists, hormones with opposing actions, or drugs which block synthesis of endogenous hormones
How do oestrogens work?
Antagonists androgen dependent prostate cancer
What are the side effects of oestrogens?
Nausea, fluid retention, thrombosis: impotence and gynaecomastia
Name 3 other hormones used in cancer treatment
Progesterones
GnRH analogues
Somatostatin analogues
What type of drug is tamoxifen?
A hormone antagonist
How does tamoxifen work?
•Competitive antagonist at oestrogen Rs → inhibits transcription of oestrogen-responsive genes → breast cancer treatment
What are the adverse effects of tamoxifen?
•Adverse effects: similar to menopausal effects, may cause endometrial cancer + ↑ risk of blood clots
What are •Letrozole/ exemastine and how do they work?
•Aromatase inhibitors
Block conversion of androgens to oestrogens
What are •Flutamide, cyproterone, bicalutamide
And which cancer are they used to treat?
Androgen antagonists - prostate cancer
•Prednisolone/ dexamethasone work by and are used for?
Inhibit lymphocyte proliferation → treatment of lymphomas/ leukaemias.
•Counter some side-effects of other anti-cancer drugs (e.g. nausea/ vomiting)
•i.e. used as supportive therapy/ in palliative care
What are Monoclonal antibodies
- Produced by cultured hybridoma cells
- React with specific target proteins expressed on cancer cells → activates immune system → lysis of cancer cells
- Some mAbs activate GF-Rs on cancer cells → inhibit survival/ promote apoptosis
What are the advantages of Ma’s?
•Advantages: targeted therapy → fewer side-effects
What are the disadvantages of Ma’s?
•Disadvantage: expensive; must be given in combination with other drugs
How does rituximab work?
Binds to CD20 protein, expressed on certain lymphoma cells → lysis of B-lymphocytes
What are the disadvantages of rituximab?
•Not all tumours have CD20
Can cause hypotension, chills + fever
•Longer term – hypersensitivity (can be fatal)
How does herceptin work?
•Binds to HER2 factor
Induces immune resp. + cell cycle inhibitors
Imatinib is a type of?
Protein kinase inhibitor
How does imatinib work?
Blocks tyrosine kinases involved in GF signaling pathways
Cytotoxic drugs often given in combination – why?
- ↑ cytotoxicity without ↑ general toxicity (i.e. drugs have diff. side-effects)
- ↓ chance of developing resistance to individual drugs
Cytotoxic drugs Often given in large doses every 2-3 weeks (usually over 6 months) – why?
- allows bone marrow to regenerate ↓ chance of developing resistance to individual drugs
- more effective than several small doses
How can you control the side effects of chemotherapy?
Control of side-effects
Nausea + vomiting (emesis)
•↓ patient compliance
•Ondansetron/ granisetron – 5HT3R antagonists → effective vs cytotoxic drug-induced vomiting
•Metoclopramide – dopamine (D2R) antagonist
0
Anxiety
•Lorazepam - anti-anxiety drug (Benzodiazepine)
Myelosuppression
•Stem cell transplant
–Autologous: stem cells harvested* from patient + infused back after chemotherapy
–Allogenic: stem cells from a matched donor
i.e. collected from blood (by dialysis) or bone marrow
