CPT: Cytotoxic chemotherapy Flashcards
Fill in the gap:
Treatmen is either or
Treatment is either curative** or **palliative.
What are goals of treatment?
Goals of therapy
- Cure or long-term survival
- Palliative - improved symptoms control; quality of life
- Side Effects - reduces Side effects to an “acceptable” level
What main treatment options are available?
What additional treatment options are available?
Main Forms of therapy
- Surgery
- Chemotherapy
- Radiotherapy
Other forms of therapy
- HIFU
- PDT
- Laser treatment
- Cryotherapy
- Sometimes more than one treatment approach is used. Cure is possible – but only in 35-40%
What are factors affecting selection of treatment?
Factors affecting selection:
- Tumour type
- Metastases
- Stage and duration
- Previous treatment
- severity and incidence of Side effects
- Age
- Sex
- Concurrent disease
- Motivation
What do cytotoxic drugs do?
What classes of chemotherapy agents is there?
- Cytotoxic drugs mainly act by damaging the cellular DNA through action on the S phase of the cell cycle. They also interfere with other vital cellular functions. Cell death results.
- They are NOT specific for tumour cells and affect ALL rapidly dividing tissue cells causing damage to “normal” healthy tissue.
Classes of Chemotherapy agents:
- Alkylating agents
- Antimetabolites
- Vinca alkaloids and Etoposide
- Cytotoxic antibiotics
- Miscellaneous
What are drug classes in alkalating agents?
How do these generally work?
Mechanism of action of alkylating agents
Alkylate within DNA at the N7 (form covalent bonds) position of guanine. This results in miscoding through abnormal base-pairing with thymine or in depurination by excision of guanine residues, leading to strand breakage
Cross-linking of DNA and ring cleavage may also occur
In all this prevents DNA separation and mRNA transcription
What are examples of nitrogen mustards - which are we going to be focusing on?
•Cyclophosphamide (Cytoxan)
- Ifosfamide
- Mechlorethamine
- Melphalan
- Chlorambucil
What can Cyclophosphamide (Cytoxan) be used for?
Side effects?
Cyclophosphamide used in lymphocytic leukaemia, lymphomas & solid tumours i.e. ovarian cancer
Side Effects
- Gametogenesis
- haemorrhagic cystitis (with high dose cyclophosphmide)
- prolonged use causes acute non-lymphocytic Leukaemia.
Alkylating-Related Agents examples
- Procarbazine
- Dacarbazine
- Altretamine
Platinum compounds:
•Cisplatin
•Carboplatin
•Oxaliplatin
What is the mechanism of action of platinum compounds?
Cisplatin/carboplatin:
60-65% intra strand GG diadducts
- 25-30% intra strand AG diadducts
- 5-10% intra strand GNG diadducts
- 1-3% intra strand GG
The mechanism of oxaliplatin has not been fully elucidated.
- These compounds alkylate N7 of guanine. They cause nephro- and ototoxicity.
- They chemically react with nucleophillic centres in the DNA with which they form platinum cross-links.
What are side effects of platinum compounds?
Cisplatin can cause:
- severe nausea and vomiting
- nephrotoxicity
- ototoxicity
- peripheral neuropathy
- hypomagnesaemia
- myelosuppression
For oxaliplatin neurotoxicity is the dose limiting SE Carboplatin is better tolerated than Cisplatin but myelosuppression is more severe
What are drug classes and examples of drugs for antimetabolites.
What characterisitic does their modes of action have?
What are examples of folic acid analogs?
Which is most of intrest to us?
•Methotrexate
- Trimetrexate
- Pemetrexed
What is folic acid and where is it sourced?
Why is it important and what is its normal pathway?
Folate
lAn essential dietary factor, from which THF cofactors are formed which provide single carbon groups for the synthesis of precursors of DNA and RNA
lTo function as a cofactor folate must be reduced by DiHydro Folate (DHF) to TetraHydroFolate (THF)
What is the mechanism of action of methotrexate?
Methotrexate resembles dihydrofolate with which it competes for the active site of the enzyme dihydrofolate reductase.
By blocking the enzyme it prevents the formation of tetrahydrofolate which is an essential co-factor for purines and pyrimidines and therefore DNA/RNA.
What is often given with metrotrexate and why?
- Folinic acid is sometimes given 24-36 hours after Methotrexate to limit the damage to normal cells.
- High-dose regimens must be followed by ‘rescue’ with folinic acid (a form of FH4)