FRACP

Question 1

Treatment in malignant pleural mesothelioma to increase OS

Answer 1

Bevacizumab, cisplatin and pemetrexed

Question 2

Doxorubicin cardiotoxicity

Answer 2

Inciidence is related to its dose!

Question 3

GnRH agonist in Prostate Ca

Answer 3

Question 4

Why give prednisolone in patient on abiraterone?

Answer 4

Question 5

Ipilimumab MOA

Answer 5

Turns off inhibitory signal of CTLA-4 - allows cytotoxic T cells to continue to destroy the cancer cells.

Question 6

Pemprolizumab MOA

Answer 6

Blocks PD1 Receptor!

Pemprolizumab - used in advanced NSCLC with PDl1 expression >50% of tumour cells. Results in longer PFS and OS with fewer SE.

Question 7

In post-menopausal patient, what is the best initial hormone therapy fort metastatic breast ca?

Answer 7

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.

Question 8

Erlotinib

Answer 8

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.

Question 9

Osimertinib MOA

Answer 9

3rd gen TKI - suprior efficacy

Irreversible inhibits both EGFR-TKI and the EGFR T790M resistance mutations!

Question 10

Who is more likely to have EGFR mutation in NSCLC?

Answer 10

young, asian, woman, lifelong non smoker

Question 11

T790M

Answer 11

EGFR T790 mutation is the most common mechanism of drug reisstance to the EGFR TKI

Question 12

Most emotegenic chemotherapy agents

Answer 12

MOST emetogenic >90%

• Cisplatin
• Cyclophosphamide

LEAST emetogenic <10%

• Bevacizumab
• Bleomycin
• Fludarabine
• Rituximab
• Vinblastine
• Vincristine
• Vinorelbine

Question 13

Denosumab

Answer 13

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

Question 14

GIST - gastrointestinal stromal tumours

Answer 14

• 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

Question 15

Most common molecular mutation in melanoma?

Answer 15

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.

Question 16

BRAF inhibitors in metastatic melanoma

Answer 16

vemurfenib + dabrafenib

Question 17

Vesicant cytotoxic drugs

Answer 17

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

Question 18

Testicular cancer

Answer 18

alpha feta protein NOT ELEVATED in pure seminomas also less aggresive

Question 19

Tumour marker with highest specificity?

Answer 19

BHCG and testicular cancer

• non seminomatous germ cell: AFP + BHCG elevated in >80%
• seminomatous germ cell tumours: BHCG elevated in <20%, AFP NEVER elevated

Question 20

Poor prognostic factors in breast cancer:

Answer 20

• • number of positive axillary nodes (DA MOST)
• • tumour size
• tumour grade
• lymphatic and vascular invasion
• ER and PR negativity

Question 21

Initial hormone therapy in metastic breast cancer in postmenopausal woman?

Answer 21

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!

Question 22

Lapatinib

Answer 22

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

Question 23

Use of HRT increases the risk of which cancer?

Answer 23

Breast Cancer!

Question 24

Tamoxifen is assoc with increase risk of which cancer?

Answer 24

endometrial cancer and uterine sarcoma

Question 25

Which antidepressant to be avoided when using tamoxifen?

Answer 25

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!

Question 26

Well known side effect of AI?

Answer 26

Osteoporosis - this effect can be prevented by small dose of biphosphonates and seems to reverse on ceasing the drug

Question 27

What is the best adjuvant therapy in posty menopausal women with early breast cancer and ER positive?

Answer 27

Aromatase inhibitor

Question 28

Metastatic breast cancer tx:

Answer 28

• 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

Question 29

Treatment in metastic breast ca with HER2 and ER/PR positive

Answer 29

trastuzumab and hormone therapy

Question 30

Tumour characteristics and prognosis

Answer 30

Question 31

Related cyclophosphamide syndromes

Answer 31

Question 32

Aprepirant MOA

Answer 32

NK-1 receptor antagonist

Question 33

Which serotonin antagnosts has the highest affinity for the 5-HT3 receptor?

Answer 33

Palonosetron- it has a 30-100 fold higher affinity for the 5HT3 receptor and longer half life (40 hours)

Question 34

Rational of reducing dose of dexamethasone when given in comibnation with aprepitant in the treatment of chemotherapy?

Answer 34

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.

Question 35

Danorubicin and rash

Answer 35

Danorubicin may cause a “radiation recall reaction” presenting as a rash over an area that previously recieved radiotherapy

Question 36

Cell cycle

Answer 36

Question 37

Karnofsky performance score

Answer 37

Used to correlate survival