Platinum Anti-cancer Agents Flashcards
What is cis-platinum effective against as an anti-cancer agent
Ovarian testicular Uterus Bladder head and neck Cervical Stomach prostate Non small cell lung
BASICALLY ALL SOLID TUMOUR BASED
Describe the chemistry of cis-platinum
Square planar geometry
Pt (II) and (IV) have the most stable and kinetically inert
Pt (II) and Pd (II) bromides and iodides = insoluble
Compare cisplatin to transplatin
- Transplatin: Cl- ligands are further apart compared to cisplatin: affects way Pt (II) can cross link on DNA
- First hydrolysis step: Transplatin is as rapid as cisplatin (half life= 2)
- Second hydrolysis step: very slow due to stabilising effect of the new trans oxygen ligand
- Difference = thermodynamic and kinetic
What is the translabelizing effect
The effect of a ligand over rate of substitution of another ligand positioned trans to it in a square planar complex
What is the mechanism of cisplatin entry into a cell
- Co-ordination occurs through N7 guanines via formation of 1,2-intrastrand cross links- due to hydrolysis
- DNA structure disruption and inhibition of replication and transcription- apoptosis
- Leads to DNA helix kinked and unable to function
What occurs in the intravenous injection of cisplatinum
- Distribution within blood stream: penetrates cell membrane
- Activation by hydrolysis within cells to allow addition to the DNA in nucleus
What are the various toxicities cisplatinum can cause
Haematologic toxicity:
Causes anaemia
Mild haematologic toxicity
Ototoxicity
Bilateral and symmetrical high frequency hearing loss
Irreversible
Caution with other drugs (aminoglycosides)
Neurotoxicity
Dose limiting toxicity
most common symptoms: peripheral neuropathy and hearing loss
Loss of vibration sensation, ankle jerks, parenthesis in hands or feet
Nephrotoxicity: dose limiting toxicity, renal damage reversible, secondary events (renal blood flow, glomerular filtration, polyuria)
Hypomagnesmia
How do you prevent nephrotoxicity
Aggressive saline hydration to increase urinary excretion
Infused over 24 hours
Avoid other nephrotoxic agents
Mg supplementation
250-1000mL saline with 2-4g of MgSO4
How do you prevent nausea and vomiting
Acute or delayed
Olanzapine or domperidone
What is carboplatin effective in and how does it react
Many solid tumours
Reactions between carboplatin + water + chloride ions lead to chelate ring opening
what are the toxicities associated with carboplatin
Moderately emetogenic
Renal impairment (Rare): mainly an unchanged drug in kidneys
Neurotoxicity: rare
Myelosupression: dose limiting toxicity
What is oxaliplatin approved for used in
Metastatic carcinoma of the colon or rectum as a combination infusion with 5-Fluorouracil and Leucovoroin (5-FU/LV)
what are the toxicities associated with oxaliplatin
GI: moderate emetogenicity, diarrhoea
Minimal hematologic toxicity: mild neutropenia and anaemia
No nephrotoxicity
Hypersntivity: mild
Neuropathy: avoid cold temp, exposure unavoidable, prolong infusion time, assess water temp
What is Nedaplatin and what is it used for
chelated glycolate ligand
Registered for: head and neck, testicular, ovarian, lung and cerivical cancer
What form are cis,carbo and nedaplatin administered as
IV
