Question 1
Which of the following medications is BEST associated with progression free survival in advanced metastatic renal cell carcinoma?
(A) Everolimus
(B) Sirolimus
(C) Sorafanib
(D) Nivolumab
(E) Ipilimumab
D: In a well designed randomised control trial, patients who had been pre-treated with angiogenic inhibitors had greater progression free survival and objective response rates, irrerspective of PDL-1 expression when compared to everolimus. Furthermore there was less severe adverse effects on nivolumab. The most significant reported effect was fatigue. For everolimus it was anaemia. Sorafanib and Sunitinib are tyrosine kinase inhibitors that are used early on. N Engl J Med 2015; 373:1803-1813
Question 2
What is true with regards to nivolumab's mechanism of action?
(A) It is an IgG1 mab targeting PD-1
(B) It is an IgG2 mab targeting PD-1
(C) It is an IgG3 mab targeting PD-1
(D) It is an IgG4 mab targeting PD-1
(E) It is an IgG1 mab targeting PDL-1 and PDL-2
D: Expert Opin Biol Ther 2013;13:847-861
Question 3
Which of the following cancers has the highest association with obesity?
(A) Uterine (endometrial)
(B) Gallbladder (cholangiocarcinoma)
(C) Kidnry
(D) Cervical
(E) Thyroid
A: Assuming causality, 41% of uterine and 10% or more of gallbladder, kidney, livr and colon cancers could be attributable to excess weight. HR for uterine cancer with obesity = 1.6 Lancet 2014, 384: 755-765
Question 4 - 9 EMQ
Match the following to the mechanism of action specific to the listed drug
(A) Microtubule assembly inhibitor
(B) Telomerase inhibitor
(C) MEK inhibitor
(D) BRAF inhibitor
(E) DNA alkylating agent
(F) DNA-cross linking agents
(G) Topoisomerase inhibitors
(H) Dihydrofolate reductase inhibitors
Dabrafenib
D
Trametanib
C
Melphalan
E
Donoroubicin
G
Carboplatin
F
Docetaxel
A
http://cw.tandf.co.uk/scottbrownent/sample-material/Chapter-4-Mechanisms-of-anticancer-drugs.pdf
Question 10
Which of the following statements is FALSE with regards to the use of androgen depravation therapy and chemotherapy in the treatment of prostate cancer
(A) Androgen depravation therapy may be used in the (neo) adjuvant setting post radiotherapy for locally advanced or localised prostate cancer
(B) In castrate naive patients, androgen depravation therapy consists of the combination of anti-androgen therapy and GnRH agonist/ orchiectomy, with the anti-androgen therapy to minimse the initial surge in FSH and LH secondary to GnRH agonists
(C) Enzalutamide acts by inhibiting CYP17, thereby decreasing extragonadal androgen biosynthesis
(D) Enzalutamide may lower the seizure threshold, and is used only in castrate resistant disease post failure with docetaxel based chemotherapy or if predicted intolerance to docetaxel chemotherapy
(E) Abiratorone when used alone may cause hypokalaemia, hypertension and fluid retention. It should always be prescribed with prednisolone
C: This is the mechanism of action of Abiratarone. Enzalutamide prevents the binding of androgens to the androgen receptor hence inhibiting receptor dimerisation. Evidence in support of (A) - Bolla NEJM 2009, Warde NEJM 2012, Evidence in support of (B) - ESMO 2015 guidelines, Evidence in support of (D) - Scher, NEJM 2012, Beer NEJM 2014, Evidence in support of (E) - deBono NEJM May 2011. Also note that docetaxel has been approved for survival in hormone sensitive metastatic prostate cancer (Sweeney NEJM August 2015).
Question 11
Which of the following treatments does not improve overall survival in hormone refractory prostate cancer?
(A) mitoxantrone
(B) Docetaxel
(C) Abirataorone
(D) Carbazitaxel
(E) Enzalutamide
A: RPA Course 2015
Question 12
A 24 year old man presents to the medical oncology clinic with a unilateral, firm left testicular mass. An ultrasound shows a hypoechoic lesion suspicious of primary malignancy. His b-HCG and AFP are elevated. What is the best method of confirming his diagnosis?
(A) FNA of mass
(B) core biopsy of mass
(C) Biopsy under surgical exploration
(D) radical inguinal orchiectomy
(E) Palpable characteristics
D: In general, biopsy of a testicular mass where malignancy has a high pre-test probability should be avoided, as this may seed the tumour into the scrotum and also change the lymphatic drainage characteristics. N Engl J Med 2014; 371:2005-2016
Question 13
A 26 year old male with stage 1 seminoma that was recently diagnosed on a radical orchiectomy presents to the oncology clinic for review. He is extremely nervous about the prospect of radiotherapy or chemotherapy. Which of the following options is most appropriate for this gentleman
(A) Active surveillance
(B) Chemotherapy with carboplatin
(C) Radiotherapy over 2 - 3 weeks
(D) Discharge from clinic
(E) Chemoradiotherapy
A: this patient is anxious about chemotherapy or radiotherapy and therefore should be actively surveilled. 5-year survival is equivalent in patients with stage 1 seminomas (defined as localised to the testes without radiological evidence of spread and normalisation of tumour markers post orchiectomy) when comparing strategy A, B and C. However, recurrence rates are higher (20% risk of relapse), and therefore the surveillance strategy must be rigorous. "According to guidelines of the National Comprehensive Cancer Network (NCCN), active surveillance consists of physical examination, measurement of levels of tumor markers (AFP and β-hCG), and abdominal and pelvic CT every 3 to 4 months for the first 2 years, every 6 to 12 months in years 3 and 4, and annually thereafter " N Engl J Med 2014; 371:2005-2016
Which of the following medications is BEST associated with progression free survival in advanced metastatic renal cell carcinoma?
(A) Everolimus
(B) Sirolimus
(C) Sorafanib
(D) Nivolumab
(E) Ipilimumab
D: In a well designed randomised control trial, patients who had been pre-treated with angiogenic inhibitors had greater progression free survival and objective response rates, irrerspective of PDL-1 expression when compared to everolimus. Furthermore there was less severe adverse effects on nivolumab. The most significant reported effect was fatigue. For everolimus it was anaemia. Sorafanib and Sunitinib are tyrosine kinase inhibitors that are used early on. N Engl J Med 2015; 373:1803-1813
Question 2
What is true with regards to nivolumab's mechanism of action?
(A) It is an IgG1 mab targeting PD-1
(B) It is an IgG2 mab targeting PD-1
(C) It is an IgG3 mab targeting PD-1
(D) It is an IgG4 mab targeting PD-1
(E) It is an IgG1 mab targeting PDL-1 and PDL-2
D: Expert Opin Biol Ther 2013;13:847-861
Question 3
Which of the following cancers has the highest association with obesity?
(A) Uterine (endometrial)
(B) Gallbladder (cholangiocarcinoma)
(C) Kidnry
(D) Cervical
(E) Thyroid
A: Assuming causality, 41% of uterine and 10% or more of gallbladder, kidney, livr and colon cancers could be attributable to excess weight. HR for uterine cancer with obesity = 1.6 Lancet 2014, 384: 755-765
Question 4 - 9 EMQ
Match the following to the mechanism of action specific to the listed drug
(A) Microtubule assembly inhibitor
(B) Telomerase inhibitor
(C) MEK inhibitor
(D) BRAF inhibitor
(E) DNA alkylating agent
(F) DNA-cross linking agents
(G) Topoisomerase inhibitors
(H) Dihydrofolate reductase inhibitors
Dabrafenib
D
Trametanib
C
Melphalan
E
Donoroubicin
G
Carboplatin
F
Docetaxel
A
http://cw.tandf.co.uk/scottbrownent/sample-material/Chapter-4-Mechanisms-of-anticancer-drugs.pdf
Question 10
Which of the following statements is FALSE with regards to the use of androgen depravation therapy and chemotherapy in the treatment of prostate cancer
(A) Androgen depravation therapy may be used in the (neo) adjuvant setting post radiotherapy for locally advanced or localised prostate cancer
(B) In castrate naive patients, androgen depravation therapy consists of the combination of anti-androgen therapy and GnRH agonist/ orchiectomy, with the anti-androgen therapy to minimse the initial surge in FSH and LH secondary to GnRH agonists
(C) Enzalutamide acts by inhibiting CYP17, thereby decreasing extragonadal androgen biosynthesis
(D) Enzalutamide may lower the seizure threshold, and is used only in castrate resistant disease post failure with docetaxel based chemotherapy or if predicted intolerance to docetaxel chemotherapy
(E) Abiratorone when used alone may cause hypokalaemia, hypertension and fluid retention. It should always be prescribed with prednisolone
C: This is the mechanism of action of Abiratarone. Enzalutamide prevents the binding of androgens to the androgen receptor hence inhibiting receptor dimerisation. Evidence in support of (A) - Bolla NEJM 2009, Warde NEJM 2012, Evidence in support of (B) - ESMO 2015 guidelines, Evidence in support of (D) - Scher, NEJM 2012, Beer NEJM 2014, Evidence in support of (E) - deBono NEJM May 2011. Also note that docetaxel has been approved for survival in hormone sensitive metastatic prostate cancer (Sweeney NEJM August 2015).
Question 11
Which of the following treatments does not improve overall survival in hormone refractory prostate cancer?
(A) mitoxantrone
(B) Docetaxel
(C) Abirataorone
(D) Carbazitaxel
(E) Enzalutamide
A: RPA Course 2015
Question 12
A 24 year old man presents to the medical oncology clinic with a unilateral, firm left testicular mass. An ultrasound shows a hypoechoic lesion suspicious of primary malignancy. His b-HCG and AFP are elevated. What is the best method of confirming his diagnosis?
(A) FNA of mass
(B) core biopsy of mass
(C) Biopsy under surgical exploration
(D) radical inguinal orchiectomy
(E) Palpable characteristics
D: In general, biopsy of a testicular mass where malignancy has a high pre-test probability should be avoided, as this may seed the tumour into the scrotum and also change the lymphatic drainage characteristics. N Engl J Med 2014; 371:2005-2016
Question 13
A 26 year old male with stage 1 seminoma that was recently diagnosed on a radical orchiectomy presents to the oncology clinic for review. He is extremely nervous about the prospect of radiotherapy or chemotherapy. Which of the following options is most appropriate for this gentleman
(A) Active surveillance
(B) Chemotherapy with carboplatin
(C) Radiotherapy over 2 - 3 weeks
(D) Discharge from clinic
(E) Chemoradiotherapy
A: this patient is anxious about chemotherapy or radiotherapy and therefore should be actively surveilled. 5-year survival is equivalent in patients with stage 1 seminomas (defined as localised to the testes without radiological evidence of spread and normalisation of tumour markers post orchiectomy) when comparing strategy A, B and C. However, recurrence rates are higher (20% risk of relapse), and therefore the surveillance strategy must be rigorous. "According to guidelines of the National Comprehensive Cancer Network (NCCN), active surveillance consists of physical examination, measurement of levels of tumor markers (AFP and β-hCG), and abdominal and pelvic CT every 3 to 4 months for the first 2 years, every 6 to 12 months in years 3 and 4, and annually thereafter " N Engl J Med 2014; 371:2005-2016
Targeted therapies in cancer
- Classes of drugs
- Small molecules (the ibs) e.g. gefitinib, erlotinib, vemurafinib
- Tyroskine kinase inhibition – sub stem “-tinib” (e.g. imatinib)
- Proteasome inhibition – ‘-zomib’ (e,g, bortezomib)
- Cycline-dependent kinase inhibition – ‘-ciclib’ (e.g. palbociclib)
- Monoclonal antibodies (the mabs) e.g. cetuximab, bevaxizumab
- Attach to receptors on the outside of cells to prevent the receptors from interacting with the signaling molecules (e.g. EGFR or VEGFR)
- Deliver radioactive molecules or toxins to the inside of the cells through attachment to cellular receptors
- Activate the body’s natural immune response
- Small molecules (the ibs) e.g. gefitinib, erlotinib, vemurafinib
- Small molecule tyrosine kinase inhibitors
- EGFR: gefitinib, afatinib, erlotinib: lung
- ALK: crizotinib, ceretinib: lung
- Her2/Neu and EGFR: Lapatinib
- Braf V600E: vemurafenib; dabrafenib
- BCR-Abl: imatinib, dasatinib, nilotinib
- Multikinase inhibitors: can be beneficial with additive affect or detrimental with more adverse events
- Imatinib: c-kit, bcr-abl PDGF: GIST, CML, DFP and others
- Nilitonib: c-kit, bcr-abl PDGF: CML and GIST
- Sunitib: VEGFR, c-kit: Renal, GIST
- Sorafenib: RET, VEGFR: renal, HCC, anaplastic thyroid cancer
- Regorafinib: c-kit, VEGFR: colon cancer, GIST
