FRACP Flashcards
Treatment in malignant pleural mesothelioma to increase OS
Bevacizumab, cisplatin and pemetrexed
Doxorubicin cardiotoxicity
Inciidence is related to its dose!
GnRH agonist in Prostate Ca
Why give prednisolone in patient on abiraterone?
Ipilimumab MOA
Turns off inhibitory signal of CTLA-4 - allows cytotoxic T cells to continue to destroy the cancer cells.
Pemprolizumab MOA
Blocks PD1 Receptor!
Pemprolizumab - used in advanced NSCLC with PDl1 expression >50% of tumour cells. Results in longer PFS and OS with fewer SE.
In post-menopausal patient, what is the best initial hormone therapy fort metastatic breast ca?
Aromatase inhibitor!
The aromatase enzyme system converts androgens into estorgens. In postmenopausal women, aromatases present in fat, liver, muscle and normal and neoplastic breast tissue convert circulating androstenedione into oestriol. Inhibition of aromatases causes a marked decrease in tissue oestrogen levels.
Erlotinib
Use in advanced NSCLC with activating EGFR mutations. Erlotinib is a tyosine kinase inhibitor.
Rash occurs with majority of patients - resmbels acne and primarliy involves ace and neck. Self limited and resolves in majoirty of cases even with continued use.
Osimertinib MOA
3rd gen TKI - suprior efficacy
Irreversible inhibits both EGFR-TKI and the EGFR T790M resistance mutations!
Who is more likely to have EGFR mutation in NSCLC?
young, asian, woman, lifelong non smoker
T790M
EGFR T790 mutation is the most common mechanism of drug reisstance to the EGFR TKI
Most emotegenic chemotherapy agents
MOST emetogenic >90%
- Cisplatin
- Cyclophosphamide
LEAST emetogenic <10%
- Bevacizumab
- Bleomycin
- Fludarabine
- Rituximab
- Vinblastine
- Vincristine
- Vinorelbine
Denosumab
Denosumab better than placebo, zoledronic acid and pamidronate in reducing the risk of fracture sin those with cancer. However Denosumab carries a higher risk for hypocalcemia (10% vs 6%) similar risk with zometa at causing osteonecrosis of teh jaw and increases the risk of skin infections.
Given as monthly inj in cancer patients
Main advantage = drug is safe to use in patients with renal impairment whereas biphosphante can potentially cause nephrotoxicity in patient with a eGFR of < 30
GIST - gastrointestinal stromal tumours
- Mesenchymal neoplasms of the GI tract and are thought to develop from the interstitial cells of Cajal, innervated cells associated with the Auerbach plexus.
- GISTS are typically define by the expression of c-KIT (CD117) in the tumor cells, as these activating KIT mutations are seen in 85-95% of GISTs
- About 3-5% of the remainder of KIT negative GISTs contain PDGFR alpha mutations
- GISTs are RARE and constitue only 1% of malignant tyumous of teh GI tract but are the most common mesenchymal neoplasm of the GI tract
Most common molecular mutation in melanoma?
BRAF!
Approx 40-60% of melanomas contain a mutation in the gene that encodes BRAF leading to constitutive activation of downstream signaling in the MAP kinase pathway
In 80-90% of the cases, the atcivating mutation consists of the substitution of glutamic acid for valine at amino acid 600 - V600E.
BRAF mutations - associated ith high-risk melanoma, earlier age of onset, lack of chronic skin damage and shortened survival.
BRAF inhibitors in metastatic melanoma
vemurfenib + dabrafenib
Vesicant cytotoxic drugs
Vesicant extravasation defined as the leakage of certain drugs called vesicants out of a vein into the tissue around it. Vesicants cause blistering and othe rtissue injury that may be severe and can lead to tissue necrosis.
List of vesicant cytotoxic drugs (commonly used):
- the VINs eg vincristine, oxaliplatin, cisplatin, docetaxelm doxoruicin (and other rubicins), paclitaxel
Testicular cancer
alpha feta protein NOT ELEVATED in pure seminomas also less aggresive
Tumour marker with highest specificity?
BHCG and testicular cancer
- non seminomatous germ cell: AFP + BHCG elevated in >80%
- seminomatous germ cell tumours: BHCG elevated in <20%, AFP NEVER elevated
Poor prognostic factors in breast cancer:
- number of positive axillary nodes (DA MOST)
- tumour size
- tumour grade
- lymphatic and vascular invasion
- ER and PR negativity
Initial hormone therapy in metastic breast cancer in postmenopausal woman?
Aromatase inhibitor! eg. anastrozole,, letrozole, exemestene
REMEMBER - AI should NOT BE used in pre-menopausal women, as AI can’t stop teh ovaries from making estrogen but rather stop the production of estrogen by blocking the enzyme aromatase. The decrease in estrogen level would ACTIVATE the hypothalamus and pituitary axis to increase gonadotropin secretion, which in turn stimulates the ovary to increase androgen production!
Lapatinib
DUAL kinase inhibitor (EGFR/HER2)
Therapeutic indications: HER2 positive overexpressing metastatic breast cancer. lapatinib + capecitabine is indicated for the treatment of patients with metastatic breast cancer whose tumours overexpress HER2 and who have progressed despite an anthracycline adn a taxane.
Can also be used if trastuzumab is not appropriate in the first line setting
SE: Anaemia, hand-foot syndrome transaminitis, diarrhoea
Use of HRT increases the risk of which cancer?
Breast Cancer!
Tamoxifen is assoc with increase risk of which cancer?
endometrial cancer and uterine sarcoma
Which antidepressant to be avoided when using tamoxifen?
Fluoxetine and paroxetine
- BOTH CYP2D6 inhibitors. They interfer with transformation of Tamoxifen to the active metabolite endoxifen. Thereby reducing Tamoxifens efficacy and increasing risk of breast cancer recurrence.
Venlafaxine DOES NOT block - therefore safe to use!
Well known side effect of AI?
Osteoporosis - this effect can be prevented by small dose of biphosphonates and seems to reverse on ceasing the drug
What is the best adjuvant therapy in posty menopausal women with early breast cancer and ER positive?
Aromatase inhibitor
Metastatic breast cancer tx:
- if brain mets + HER2 positive = chemo and labatinib (crosses BBB)
- if lytic bone mets - biphosphanates
- if rapidly progressive - trastuzumab
- if isolated single mets - local therapy
Treatment in metastic breast ca with HER2 and ER/PR positive
trastuzumab and hormone therapy
Tumour characteristics and prognosis
Related cyclophosphamide syndromes
Aprepirant MOA
NK-1 receptor antagonist
Which serotonin antagnosts has the highest affinity for the 5-HT3 receptor?
Palonosetron- it has a 30-100 fold higher affinity for the 5HT3 receptor and longer half life (40 hours)
Rational of reducing dose of dexamethasone when given in comibnation with aprepitant in the treatment of chemotherapy?
To prevent dexamethasone toxicity
Aprepitant is a CYP34A inhibitor which is responsible for the metabolism of corticosteroid.
Therefore dose reduction of corticosteroid is required to prevent toxicity.
Danorubicin and rash
Danorubicin may cause a “radiation recall reaction” presenting as a rash over an area that previously recieved radiotherapy
Cell cycle
Karnofsky performance score
Used to correlate survival
