AOCNP Cancer Pharmacology and Chemotherapy 5 — Questions and Answers
Question 1: Which statement best describes the mechanism of resistance to imatinib in chronic myeloid leukemia (CML)?
- Overexpression of topoisomerase II preventing drug binding
- Point mutations in the BCR-ABL kinase domain, particularly T315I (Correct answer)
- Increased expression of VEGF bypassing BCR-ABL signaling
- Upregulation of mismatch repair genes
Correct answer: Point mutations in the BCR-ABL kinase domain, particularly T315I
The T315I gatekeeper mutation in BCR-ABL is the most common and problematic resistance mutation, conferring resistance to first- and second-generation TKIs.
Question 2: A patient receiving cisplatin-based chemotherapy develops severe nausea and vomiting despite standard antiemetics. Which agent targets substance P/NK-1 receptors and is most appropriate to add?
- Ondansetron
- Aprepitant (Correct answer)
- Metoclopramide
- Lorazepam
Correct answer: Aprepitant
Aprepitant is a neurokinin-1 (NK-1) receptor antagonist that blocks substance P binding, effective for delayed emesis associated with highly emetogenic chemotherapy.
Question 3: Which of the following describes the pharmacodynamic rationale for using leucovorin (folinic acid) in combination with 5-fluorouracil (5-FU)?
- Leucovorin reduces 5-FU-induced nephrotoxicity
- Leucovorin stabilizes the ternary complex of 5-FU with thymidylate synthase, enhancing inhibition (Correct answer)
- Leucovorin increases 5-FU bioavailability by inhibiting CYP2A6
- Leucovorin acts as a rescue agent to prevent 5-FU toxicity
Correct answer: Leucovorin stabilizes the ternary complex of 5-FU with thymidylate synthase, enhancing inhibition
Leucovorin provides reduced folate that stabilizes the ternary complex between FdUMP (5-FU metabolite) and thymidylate synthase, enhancing its cytotoxic effect.
Question 4: An oncology nurse practitioner is reviewing a patient on enzalutamide for metastatic castration-resistant prostate cancer. Which CNS toxicity requires patient counseling?
- Peripheral neuropathy and foot drop
- Seizures, which occur in approximately 1% of patients (Correct answer)
- Cognitive impairment and dementia within 6 months
- Ototoxicity with high-frequency hearing loss
Correct answer: Seizures, which occur in approximately 1% of patients
Enzalutamide has seizurogenic potential, occurring in ~1% of patients, and patients should be counseled to avoid driving and activities requiring alertness if seizures occur.
Question 5: A patient is receiving pemetrexed for mesothelioma. Which supplementation is required to reduce hematologic and GI toxicity?
- Pyridoxine (B6) and magnesium supplementation
- Folic acid and vitamin B12 supplementation (Correct answer)
- Leucovorin rescue 24 hours after each dose
- Iron supplementation and erythropoietin
Correct answer: Folic acid and vitamin B12 supplementation
Folic acid (daily, starting 7 days before) and vitamin B12 (IM, every 9 weeks) supplementation are required to reduce pemetrexed-related hematologic and GI toxicities.
Question 6: Which of the following correctly describes the mechanism of action of CDK4/6 inhibitors such as palbociclib in hormone receptor-positive breast cancer?
- Block estrogen receptor binding in the nucleus
- Inhibit cyclin-dependent kinases 4 and 6, preventing Rb phosphorylation and halting cell cycle at G1/S checkpoint (Correct answer)
- Promote degradation of the estrogen receptor via PROTAC mechanism
- Inhibit HER2 dimerization preventing downstream MAPK signaling
Correct answer: Inhibit cyclin-dependent kinases 4 and 6, preventing Rb phosphorylation and halting cell cycle at G1/S checkpoint
Palbociclib inhibits CDK4/6, keeping Rb in its hypophosphorylated active state, which sequesters E2F transcription factors and blocks G1-to-S phase progression.
Question 7: A patient on CHOP chemotherapy (cyclophosphamide, doxorubicin, vincristine, prednisone) presents with constipation, abdominal distension, and absent bowel sounds. Which agent is most likely responsible?
- Cyclophosphamide causing hemorrhagic enteritis
- Vincristine causing autonomic neuropathy and paralytic ileus (Correct answer)
- Doxorubicin causing mucosal damage and dysmotility
- Prednisone causing peptic ulcer disease
Correct answer: Vincristine causing autonomic neuropathy and paralytic ileus
Vincristine's neurotoxicity includes autonomic dysfunction, which can manifest as paralytic ileus requiring dose reduction or schedule adjustment.
AOCNP Cancer Pharmacology and Chemotherapy 5
Which statement best describes the mechanism of resistance to imatinib in chronic myeloid leukemia (CML)?