9 Systemic Therapy for Cancer

Sara K. Butler and Leigh M. Boehmer

QUESTIONS

Each of the numbered items below is followed by lettered answers. Select the ONE lettered answer that is BEST in each case, unless instructed otherwise.

Question 9.1 Interindividual pharmacokinetic/pharmacodynamic variability can be a result of which of the following principles?

A. Dose proportionality

B. Feedback-controlled dosing

C. Therapeutic drug monitoring

D. Sex dependence

Question 9.2 A 35-year-old female is currently being treated with pazopanib (CYP3A4 substrate). She is admitted for seizure management and the consult team recommends initiation of phenytoin. What effect may concurrent administration have on pazopanib concentrations?

A. Decrease pazopanib concentration

B. Increase pazopanib concentration

C. No change in pazopanib concentration

D. None, if the pazopanib is taken with food

Question 9.3 Which of the following scenarios best identifies a prognostic marker?

A. KRAS mutation testing in setting of colon cancer

B. Dihydropyrimidine dehydrogenase (DPD) deficiency in the setting of 5-FU therapy

C. MMR protein expression deficiency in setting of colon cancer

D. UGT1A1*28 polymorphism in setting of irinotecan therapy

Question 9.4 HG is a 55-year-old patient with BRAF mutation positive, metastatic melanoma on vemurafenib therapy. Despite an initial dramatic response, his disease relapsed after roughly 6 month of treatment. Which of the following explanations describes the most likely mechanism of resistance?

A. KRAS mutation

B. MEK mutation

C. T790M mutation

D. T315I mutation

Question 9.5 Which of the following medication:pharmacogenomic assay pairs are correctly matched (select two correct responses)?

A. 6-mercaptopurine:thiopurine methyltransferase (TPMT) activity

B. Tamoxifen:uridine diphosphate glucuronosyltransferase (UGT) 1A1 activity

C. 5-fluorouracil:dihydropyrimidine dehydrogenase (DPD) activity

D. Afatinib:anaplastic lymphoma kinase (ALK) gene rearrangement

Question 9.6 Which of the following is CORRECT regarding hemorrhagic cystitis?

A. Bladder protection with mesna is required for all patients receiving cyclophosphamide

B. Hemorrhagic cystitis is caused by indirect damage to the bladder wall by either cyclophosphamide or ifosfamide

C. Mesna works by providing a free sulfhydryl group that binds to toxic metabolites

D. Mesna should be given in divided doses to total 100% of the total alkylating agent dose

Question 9.7 RT is a 50-year-old female with progressive disease following two cycles of carboplatin and paclitaxel for advanced ovarian cancer. Based on our current understanding, which of the following mechanisms may best explain platinum-resistant tumor cells (select two correct responses)?

A. Decreased damage tolerance

B. Reduced cellular accumulation

C. Inactivation of autophagy

D. Intracellular detoxification

Question 9.8 PL is a-65 year-old patient with newly diagnosed metastatic non–small cell lung adenocarcinoma scheduled to begin treatment with cisplatin and pemetrexed in 1 week. Which of the following medications should be started today to help minimize hematologic toxicities with pemetrexed?

A. Vitamin B₆ and Vitamin B₁₂

B. Folic acid and dexamethasone

C. Folinic acid and Vitamin B₆

D. Vitamin B₁₂ and folic acid

Question 9.9 Which of the following statements is CORRECT regarding anthracycline cardiotoxicity?

A. Acute doxorubicin cardiotoxicity is irreversible, and its incidence can be reduced by increasing infusion rates.

B. Chronic and delayed anthracycline cardiotoxicity is more common and severe because it is irreversible.

C. The incidence of cardiomyopathy secondary to anthracyclines is only related to the cumulative dose.

D. Available evidence suggests the superiority of β-blocker use to prevent anthracycline cardiotoxicity.

Question 9.10 NB is a 68-year-old patient with hormone-refractory metastatic prostate cancer with progressive disease, including brain metastases, after docetaxel treatment. In discussing the possible role for cabazitaxel in this situation with the patient, which of the following statements are CORRECT (select two correct responses)?

A. Cabazitaxel penetrates the blood–brain barrier

B. Cabazitaxel is an excellent substrate for the multidrug resistance P-glycoprotein pump

C. Cabazitaxel binds to and stabilized the α-tubulin subunit causing cell-cycle arrest

D. Cabazitaxel is active against prostate cancers that are sensitive and resistant to docetaxel

Question 9.11 Which of the following kinase inhibitors were originally developed as a direct inhibitor of a mutated/amplified tyrosine kinase (select two correct responses)?

A. Imatinib for the treatment of GIST

B. Erlotinib for the treatment of non–small cell lung cancer

C. Lapatinib for the treatment of HER2-positive breast cancer

D. Vandetanib in the treatment of medullary thyroid cancer

Question 9.12 Which of the following is a CORRECT statement regarding the role of VEGF inhibition in the treatment of kidney cancer?

A. VEGF inhibitors like pazopanib or sunitinib are effective in the treatment of kidney cancer due to known kinase mutations in VEGF.

B. The mechanism in which mTOR inhibitors are effective in the treatment of kidney cancer is solely based on the antiproliferative impact against endothelial cells resulting in anti-angiogensis.

C. The increase activation of the hypoxia inducible factor (HIF) pathway results in activation of downstream target genes such as VEGF.

D. Inhibition of VEGF via bevacizumab has resulted in greater disease response than inhibition of VEGF via multikinase inhibitors such as sunitinib or sorafenib.

Question 9.13 LB is a 63-year-old patient with newly diagnosed metastatic melanoma. His tumor was sent for mutational analysis and was found to be BRAF V600E mutation positive. Which of the following is a CORRECT statement regarding treatment of his tumor?

A. Due to sorafenib’s inhibition of RAF, it can be used as initial therapy.

B. BRAF inhibition is the most important part of his therapy and treatment with a MEK inhibitor should not be considered.

C. BRAF inhibitors are only approved in the second-line setting and LB should be initiated on either cytotoxic chemotherapy or immunotherapy with ipilimumab.

D. High serum levels of BRAF inhibitors are important to allow for achieving adequate pathway inhibition.

Question 9.14 Which of the following is a principle of epigenetic therapy?

A. Epigenetic changes cause alterations in the sequencing of targeted genes.

B. Epigenetic therapy is mostly utilized and has the greatest efficacy in solid tumors.

C. The impact of epigenetic therapy is not seen immediately due to efficacy being based on cellular reprogramming.

D. Combination therapy with HDAC inhibitors and demethylating agents should not be pursued due overlapping toxicities.

Question 9.15 PM is an 82-year-old male with newly diagnosed multiple myeloma who presents for discussion of management of his disease. Past medical history is significant for diabetes, peripheral neuropathy, hyperthyroidism, and hypertension. Which of the following would be the most appropriate management of his cancer?

A. Bortezomib 1.3 mg/m² subcutaneously on days 1, 4, 8, and 11 and dexamethasone.

B. Carfilzomib 20 mg/m² IV on days 1, 2, 8, 9, 15, and 16 and dexamethasone.

C. Bortezomib 1.3 mg/m² IV on days 1, 4, 8 and 11 and dexamethasone.

D. Carfilzomib 27 mg/m² IV on days 1, 2, 8, 9, 15, and 16 and dexamethasone.

Question 9.16 Poly (ADP-ribose) polymerase (PARP) signals the presence of DNA damage and facilitates DNA repair. Which of the following is a role for PARP inhibition? (Select two correct responses).

A. Chemopotentiation

B. Serine/threonine kinase inhibition

C. Synthetic lethality with BRCA 1/2 mutations

D. Increased hypoxia-inducible factor-1 function

Question 9.17 Asparaginase is commonly used in combination with methotrexate as part of acute lymphoblastic leukemia treatment protocols. Which of the following statements regarding administration of these drugs is TRUE?

A. Asparaginase should be given concurrently with methotrexate in order to inhibit methotrexate’s clearance and increase its cytotoxicity.

B. Asparaginase should be given immediately before methotrexate in order to decrease the risk of methotrexate neurotoxicity.

C. Asparaginase should be given 12 hours before methotrexate in order to prime cancer cells for methotrexate’s antimetabolite activity.

D. Asparaginase and methotrexate should be given sequentially at least 24 hours apart secondary to methotrexate antagonism.

Question 9.18 SB is a patient with metastatic prostate cancer who presents to the clinic with hypokalemia and peripheral edema. He recently started on abiraterone 1,000 mg po daily after disease progression on docetaxel. Which of the following would be the most appropriate treatment options?

A. Switch the patient to enzalutamide therapy.

B. Decrease the dose of abiraterone to 750 mg po daily.

C. Initiate prednisone 5 mg po twice daily.

D. Initiate spironolactone 50 mg po daily.

Question 9.19 Which of the following statements regarding antiangiogenesis agents is CORRECT?

A. Lenalidomide was the first angiogenesis inhibitor approved by the FDA for cancer treatment.

B. Vorinostat, celecoxib, and bortezomib may all be referred to as exclusive angiogenesis inhibitors.

C. Proangiogenic factors include endostatin, angiostatin, and thrombospondin.

D. Resistance to vascular endothelial growth factor inhibitors has been seen secondary to increased expression of proangiogenic factors.

Question 9.20 TB is a 72-year-old male with progressive CLL who is about to initiate therapy with ofatumumab. Which of the following are considered advantages to ofatumumab over rituximab therapy?

A. Ofatumumab induces more antibody-dependent cell-mediated toxicity (ADCC) than rituximab.

B. Ofatumumab causes more complement activation than rituximab.

C. Ofatumumab is a humanized monoclonal antibody whereas rituximab is chimeric.

D. Ofatumumab demonstrated about an 80% response rate in treatment refractory disease.

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