Cancer Chemotherapy Flashcards
What is the fractional cell kill hypothesis?
- Repeated doses of chemotherapeutic given
- Allows time for bone marrow cells to recover (recover more quickly) than tumour cells
- Get an overall reduction in tumour cells
What cancers are highly sensitive to chemotherapy?
- Lymphomas
- Germ cell tumours
- Small cell lung
- Neuroblastoma
- Wilm’s tumour
What cancers have modest sesnsitivity to chemotherapy?
- Breast
- Colorectal
- Bladder
- Ovary
- Cervix
Which tumours have low sensitivity to chemotherapy?
- Prostate
- Renal Cell
- Brain tumours
- Endometrial
How do different chemotherapeutic agents target cancer cells?
Explain how alkylating agents work
- Alkylating agent forms bond between 2 strands of DNA
- Cannot replicate at replication fork- induces double strand break
- Cell dies by apoptosis
How do Platinum compounds inhibit DNA replciation?
- Form inter and intrasand adducts → inhibits DNA synthesis
- Bulky adducts are difficult to repair
- Cells die
Explain the mechanism of action of 5-Flurouracil as a chemotherapy agent
- 5-FU inhibits thymidylate synthase
- Thymidylate synthase needed for the synthesis of folic acid
- Without folic acid- DNA and protein synthesis is reduced
Explain the mechanism of action of methotrexate
- Methotrexate inhibits dihydrofolate reductase
- Cannot form tetrahydrofolate so cannot form purines/ amino acids
Explain the mechanism of action of spindle poisons
- Spindles essential to move sister chromatids apart to opposite poles during mitosis
- Microtubule binding agents either:
- inhibit polymerisation
- stimulate polyermisate and prevent depolymerisation
Explain how Vinca alkaloids work
- Soluble alpha and betal tubulin normally form microtubule polymers
- Vinca alkaloid binds to the individual tubulins to prevent polymerisation
- Microtubules cannot form and DNA cannot replicate
Give an example of a vinca alkaloid
Vincristine
Explain how taxanes work
- Bind to the microtuble polymer and prevent its depolarisation
- Mitosis fails
Give an example of a taxane
Paclitaxel
Give 3 examples of how cells can develop resistance mechanisms to alkylating agents
- Decreased entry or increased exit of agent
- Inactivation of agent in cell → glutathione can mop up active moeity neutralising agent
- Enhanced repiar of DNA lesions produced by alkylation
What factors influence predicted response to chemotherapeutic agents?
- performance score
- clinical staging
- prognostic factors (biological factors)
- molecular or cytogenetic markers
What are the different types of IV pump for administering chemotherapy drugs?
PICC line- goes into large veins in the arm
Hickman line- direct to superior vena cava. Often better as repeated cycles of chemo can damage veins
What are some of the side effects of chemotherapy?
How can chemotherapy lead to acute renal failure
- Rapid lysis of tumour releases lots of urate crystals → hyperuricaemia
- Urate crystals precipitate in renal tubules
- Unacceptable outcome today- pre-treatment given to prevent this
What are the different patterns of vomiting in chemotherapy?
- Acute phase- 4-12 hours
- Delayed onset - 2-5 days later
- Chronic phase - may last up to 14 days
What local skin toxicity can occur from chemotherapy drugs?
- Irritation and thrombophlebitis of veins
- Extravasation (leakage of IV drugs to extravascular tissue surrounding injection site)
What general skin toxicity can occur from chemotherapy drugs such as bleomycin?
- Hyperkeratosis
- Hyperpigmentation
- Ulcerated pressure sores
What is mucositis?
- Damage to the epithelia of the GI tract
- May be profound and involve with whole tract
- Most commonly worst in the oropharynx, presents as:
- sore mouth/ throat
- diarrhoea
- G.I bleed
Which chemotherapy drugs are at high risk of causing cardio-myopathy?
- Doxorubicin
- High dose cyclophosphamide
What lung toxicity can occur from chemotherapy?
- Bleomycin (testicular tumour treatment) can cause pulmonary fibrosis
- common in many drugs
Why must chemotherapy drugs be prescribed by a specialist?
- Narrow therapeutic index
- Significant side effect profile
- Dose needs altering for the individual patient
What factors of chemotherapy drugs/ cancer patients cause abnormalities in drug absorption?
- Nausea and vomiting
- Compliance
- Gut problems
What factors of chemotherapy drugs/ cancer patients cause abnormalities in drug distribution?
- Weight loss
- Reduced body fat
- Ascites → drugs accumulate in fluid causing toxicity over time
What factors of chemotherapy drugs/ cancer patients cause abnormalities in drug elmination?
- Liver and renal dysfunction
- Other medications
What factors of chemotherapy drugs/ cancer patients cause abnormalities in protein binding?
- Low albumin (if nutrition is low)
- Other drugs
Give some important drug interactions of chemotherapy agents: Vincristine, capecitabine (oral 5FU), Methotrexate
- Vincrinstine and intaconazole (antifungal) → leads to neuropathy
- Capecitabine and warfarin
- Methotrexate and penicillin and NSAIDs
- Capecitabine and St John’s Wort, grapefruit juice
What is neoadjuvant chemotherapy?
Given before surgery/ radiotherapy for the primary cancer
What is adjuvant chemotherapy?
Given after surgery to excise the primary cancer, aiming to reduce relapse risk e.g. breast cancer
What is palliative chemotherapy?
To treat current or anticipated symptoms without curative treatment
What is primary chemotherapy?
1st line treatment for cancer… in many haematological cancers this is with curative intent
What is salvage chemotherapy?
Chemotherapy for relapsed disease
