BCPS Oncology & Hematology Pharmacotherapy 1 — Questions and Answers
Question 1: Methotrexate exerts its cytotoxic effect primarily by inhibiting which enzyme?
- Thymidylate synthase
- Dihydrofolate reductase (DHFR) (Correct answer)
- Ribonucleotide reductase
- Topoisomerase II
Correct answer: Dihydrofolate reductase (DHFR)
Methotrexate competitively inhibits DHFR, blocking reduction of folate to tetrahydrofolate and ultimately impairing DNA synthesis.
Question 2: A patient is diagnosed with Philadelphia chromosome-positive CML in chronic phase. Which of the following represents the most appropriate initial therapy?
- Hydroxyurea monotherapy
- A BCR-ABL tyrosine kinase inhibitor (TKI) (Correct answer)
- Allogeneic hematopoietic stem cell transplant
- Interferon-alpha
Correct answer: A BCR-ABL tyrosine kinase inhibitor (TKI)
BCR-ABL TKIs (imatinib, dasatinib, nilotinib, or bosutinib) are the standard first-line therapy for chronic phase CML, targeting the fusion protein created by the Philadelphia chromosome.
Question 3: Which combination of laboratory abnormalities is characteristic of tumor lysis syndrome (TLS)?
- Hyperkalemia, hyperphosphatemia, hypocalcemia, hyperuricemia (Correct answer)
- Hypokalemia, hypophosphatemia, hypercalcemia, hypouricemia
- Hypernatremia, hyperchloremia, metabolic alkalosis
- Hyperkalemia, hypomagnesemia, hyperglycemia
Correct answer: Hyperkalemia, hyperphosphatemia, hypocalcemia, hyperuricemia
TLS classically presents with hyperkalemia, hyperphosphatemia, hypocalcemia (from calcium-phosphate precipitation), and hyperuricemia from massive nucleic acid breakdown.
Question 4: For a patient receiving highly emetogenic chemotherapy (HEC) such as cisplatin, which antiemetic regimen is recommended for acute emesis prevention?
- Metoclopramide alone
- A 5-HT3 antagonist as monotherapy
- A 5-HT3 antagonist + NK1 receptor antagonist + dexamethasone (Correct answer)
- Lorazepam + prochlorperazine
Correct answer: A 5-HT3 antagonist + NK1 receptor antagonist + dexamethasone
ASCO and NCCN guidelines recommend triple antiemetic therapy combining a 5-HT3 antagonist, NK1 receptor antagonist, and dexamethasone for highly emetogenic chemotherapy.
Question 5: A patient receiving chemotherapy develops a fever of 38.5°C with an absolute neutrophil count (ANC) of 400 cells/mm³. Which initial antibiotic regimen is most appropriate?
- Oral ciprofloxacin + amoxicillin-clavulanate
- IV antipseudomonal beta-lactam monotherapy (e.g., piperacillin-tazobactam) (Correct answer)
- IV vancomycin alone
- IV cefazolin
Correct answer: IV antipseudomonal beta-lactam monotherapy (e.g., piperacillin-tazobactam)
IDSA guidelines recommend IV antipseudomonal beta-lactam monotherapy as empiric first-line treatment for febrile neutropenia in high-risk patients.
Question 6: R-CHOP is a standard regimen for diffuse large B-cell lymphoma (DLBCL). Which of the following correctly identifies all five components?
- Rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone (Correct answer)
- Rituximab, carboplatin, hydroxydaunorubicin, oxaliplatin, prednisone
- Rituximab, cyclophosphamide, hydroxyurea, omeprazole, prednisolone
- Rituximab, cetuximab, hydroxychloroquine, oxaliplatin, paclitaxel
Correct answer: Rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone
R-CHOP consists of Rituximab, Cyclophosphamide, doxorubicin (Hydroxydaunorubicin), vincristine (Oncovin), and Prednisone.
Question 7: Leucovorin (folinic acid) is administered after high-dose methotrexate to rescue normal cells. Its mechanism is to:
- Directly inhibit methotrexate uptake into cells via folate transporters
- Bypass DHFR inhibition by providing reduced folate directly (Correct answer)
- Enhance renal methotrexate elimination via alkalinization
- Chelate methotrexate and inactivate it in plasma
Correct answer: Bypass DHFR inhibition by providing reduced folate directly
Leucovorin provides 5-formyl-tetrahydrofolate directly, bypassing the DHFR blockade caused by methotrexate and rescuing normal cells without needing DHFR.
BCPS Oncology & Hematology Pharmacotherapy 1
Methotrexate exerts its cytotoxic effect primarily by inhibiting which enzyme?