Term
| Examples of Alkylating Agents |
|
Definition
- Cyclophosphamide
- Melphalan
- Busulfan
|
|
|
Term
| Mechanism of Action of Alkylating Agents |
|
Definition
| Interfere with DNA synthesis by cross-linking DNA strands --> strand breaks; inhibit DNA replication/repair |
|
|
Term
| Side Effects of Cyclophosphamide |
|
Definition
- Haemorrhagic cystitis
- Bladder TCC
|
|
|
Term
| Side Effects of All Alkylating Agents |
|
Definition
- Infertility
- Myelosuppression
- Teratogenic (never in pregnancy unless the life of the mother is at stake)
- Secondary malignancy (AML, lymphoma)
|
|
|
Term
| What class of anti-neoplastic agents confers risk of secondary malignancy? |
|
Definition
| Alkylating agents (AML, lymphoma) |
|
|
Term
| Indications for Cyclophosphamide |
|
Definition
- Haematological malignancies
|
|
|
Term
| Examples of platinum-based chemotherapeutics |
|
Definition
- Cisplatin
- Carboplatin
- Oxaliplatin
|
|
|
Term
| Mechanism of action of platinum-based chemotherapeutics |
|
Definition
| Causes cross-links of DNA |
|
|
Term
| Side effects common to all platinum-based chemotherapeutics |
|
Definition
- Infertility
- Hypomagnesaemia
- Peripheral neuropathy with cumulative dosing
|
|
|
Term
| Side effects of cisplatin |
|
Definition
- Severe nausea & vomiting
- Ototoxicity
- Nephrotoxicity
|
|
|
Term
|
Definition
|
|
Term
| Mechanism of action of Taxanes |
|
Definition
| Prevents microtubule formation by binding to tubulin dimers (M phase of cell cycle) |
|
|
Term
|
Definition
- Peripheral neuropathy
- Fluid retention
- Neutropaenia
- Infertility, amenorrhoea
- Hypersensitivity reaction
- Need to dose reduce in liver impairment
|
|
|
Term
| Mechanism of Action of, and indications for Tamoxifen |
|
Definition
ER+ competitive antagonism
ER+ Breast Ca (pre- and post-menopausal) |
|
|
Term
| Mechanism of action of, and indications for, Aromatase Inhibitors |
|
Definition
|
|
Term
| Side effects of Tamoxifen |
|
Definition
- Hot flushes
- Low libido
- DVT (2-3x risk)
- Endometrial cancer (2-3x risk)
|
|
|
Term
| Side effects of Aromatase Inhibitors |
|
Definition
- Hot flushes
- Low libido
- Arthralgias
- Osteopaenia
|
|
|
Term
| Examples of ALK-Inhibitors |
|
Definition
- Alectinib (2nd gen, new standard of care, brain penetration)
- Crizotinib (1st gen, lots of side effects)
- Others: Ceritinib, lorlatinib (brain penetration)
|
|
|
Term
| What is the function of ALK? |
|
Definition
Transmembrane tyrosin kinase receptor
Activates a whole bunch of pathways (JAK, STAT, mTOR, sonic hedgehog & more) to stimulate cell growth, transformation, and anti-apoptotic signalling |
|
|
Term
| What malignancies are ALK-Inhibitors used for? |
|
Definition
| NSCLC (5% of adenocarcinomas are ALK+, typically younger patients, non-smokers) |
|
|
Term
| Side effects of ALK-Inhibitors |
|
Definition
First generation (crizotinib) is the worst
- Nausea, vomiting, diarrhoea (mild)
- Hepatitis (severe, rare)
- Pneumonitis (severe, rare)
- Visual phenomena
- Low testosterone (universal)
- Bradycardia
|
|
|
Term
| What are some examples of intracellular EGFR inhibitors? |
|
Definition
- Erlotinib, gefitinib (1st gen)
- Afatinib (2nd gen)
- Osimertinib (3rd gen)
|
|
|
Term
| Side effects of EGFR inhibitors |
|
Definition
Acneform rash = means that it's working!
Diarrhoea
Hepatitis, pneumonitis (rare) |
|
|
Term
| Why would you use Osimertinib rather than an earlier generation EGFR inhibitor? |
|
Definition
Overcomes resistance to earlier generation EGFR inhibitors
- 50% of patients develop T790M mutation - change to structure of binding pocket meaning older EGFR-i's can't bind
- Osimertinib overcomes this
|
|
|
Term
| What is the mechanism of action of Imatinib? |
|
Definition
| Multi-kinase inhibitor, including BCR-Abl and cKIT |
|
|
Term
| What are some other multi-kinase inhibitors similar to Imatinib? |
|
Definition
|
|
Term
| Mechanism of Action of Durvalumab |
|
Definition
|
|
Term
| Indications for Durvalumab |
|
Definition
- Stage 3 Lung Ca - Neoadjuvant (PACIFIC trial)
|
|
|
Term
| Mechanism of action of Capecitabine |
|
Definition
Anti-metabolite (pyrimidine analogue)
Plantar-palmar erythema |
|
|
Term
| What are some examples of extracellular EGFR inhibitors? |
|
Definition
|
|
Term
| Side effects of VEGF inhibitors |
|
Definition
- Hypertension - means that it's working!
- Proteinuria/nephrotic syndrome
- Bleeding/increased risk of haemorrhage
- Delayed wound healing
|
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