Question
1: A 65-year-old patient with metastatic non-small cell lung cancer (NSCLC) positive for an EGFR exon 19 deletion is being treated with osimertinib. After 18 months, the patient shows signs of clinical progression. A repeat biopsy reveals the acquired EGFR T790M mutation is no longer present, but a new MET amplification is detected. Which of the following therapeutic strategies is most rationally based on this molecular evolution?
(a) Continuing osimertinib at an increased dose.
(b) Switching to a first-generation EGFR TKI like gefitinib.
(c) Adding a c-MET inhibitor such as capmatinib or tepotinib to osimertinib.
(d) Discontinuing EGFR TKI therapy and initiating platinum-doublet chemotherapy.
(e) Switching to an ALK inhibitor due to potential pathway crosstalk.
2: A patient with castration-resistant prostate cancer (CRPC) is initiated on abiraterone acetate. Which of the following concomitant medications requires the most careful monitoring and potential dose adjustment due to a significant interaction with abiraterone's inhibition of CYP17A1 and its downstream effects, as well as its impact on other CYP enzymes?
(a) Paracetamol for pain relief.
(b) Amlodipine for hypertension.
(c) Dexamethasone, when used at higher doses than the standard co-prescribed prednisone/prednisolone.
(d) Warfarin for atrial fibrillation.
(e) Metformin for type 2 diabetes.
3: A 58-year-old female with HER2-positive metastatic breast cancer develops Grade 3 diarrhea (7 stools per day over baseline, interfering with ADLs) within 72 hours of starting neratinib as extended adjuvant therapy. She has no other significant symptoms. What is the most appropriate initial pharmacological intervention, beyond loperamide, specifically considering neratinib's mechanism of toxicity?
(a) Prophylactic colestipol or budesonide initiated with neratinib.
(b) Intravenous fluid resuscitation and broad-spectrum antibiotics.
(c) Immediate discontinuation of neratinib and initiation of octreotide.
(d) Adding an H2 receptor antagonist like famotidine.
(e) Empiric treatment with oral vancomycin for possible C. difficile infection.
4: Which of the following statements most accurately describes a critical pharmacological consideration when using enfortumab vedotin for metastatic urothelial cancer?
(a) It is contraindicated in patients with moderate to severe renal impairment (CrCl < 30 mL/min) due to predominant renal excretion of the MMAE payload.
(b) Concomitant use of strong CYP3A4 inhibitors can significantly increase the risk of hyperglycemia.
(c) The primary dose-limiting toxicity is myelosuppression, particularly febrile neutropenia.
(d) Its use is associated with a high risk of severe peripheral neuropathy, which is often irreversible even after drug discontinuation.
(e) The risk of severe cutaneous adverse reactions (SCARs), including SJS/TEN, necessitates careful skin monitoring and patient education.
5: A patient is receiving high-dose methotrexate (HD-MTX) at 5 g/m2 for primary CNS lymphoma. Despite adequate hydration and urine alkalinization, their 48-hour methotrexate level is 3 µmol/L. Glucarpidase is administered. What is the most accurate statement regarding monitoring methotrexate levels immediately after glucarpidase administration?
(a) Immunoassay-based methotrexate tests will show an immediate and accurate reflection of the reduced systemic methotrexate levels.
(b) Methotrexate levels measured by HPLC will be falsely elevated for up to 48 hours due to interference from glucarpidase metabolites.
(c) Immunoassay-based methotrexate tests may show falsely elevated levels for several days due to DAMPA (a methotrexate metabolite acted upon by glucarpidase), requiring reliance on HPLC/LC-MS methods if available, or clinical judgment.
(d) Glucarpidase primarily enhances renal excretion of methotrexate, so urine output becomes the best surrogate marker.
(e) Leucovorin rescue should be immediately discontinued as glucarpidase has fully mitigated methotrexate toxicity.
6: A patient with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) is being considered for polatuzumab vedotin in combination with bendamustine and rituximab (Pola-BR). The patient has a baseline platelet count of and Grade 1 peripheral neuropathy. Which characteristic of polatuzumab vedotin is most critical to consider for dose modification or careful monitoring in this specific patient?
(a) Its significant potential for causing severe infusion reactions.
(b) The risk of profound and prolonged myelosuppression, particularly thrombocytopenia.
(c) Its known association with reactivation of hepatitis B virus.
(d) The potential for exacerbating pre-existing cardiac dysfunction.
(e) Its primary metabolism and excretion via the renal route.
7: Regarding the pharmacology of modern antiemetic regimens for highly emetogenic chemotherapy (HEC), which statement most accurately reflects current understanding and best practice?
(a) Dexamethasone's primary antiemetic effect in HEC is mediated through potent 5-HT3 receptor antagonism.
(b) Olanzapine provides broad antiemetic coverage primarily by antagonizing dopamine D2 and histamine H1 receptors, with lesser effects on 5-HT2A/C and 5-HT3 receptors.
(c) Aprepitant, a neurokinin-1 (NK-1) receptor antagonist, requires dose reduction in moderate hepatic impairment due to extensive first-pass metabolism.
(d) Second-generation 5-HT3 receptor antagonists like palonosetron offer significantly longer half-lives but have a higher propensity for QTc prolongation compared to first-generation agents.
(e) The addition of an NK-1 receptor antagonist to a 5-HT3 receptor antagonist and dexamethasone primarily improves control of acute, rather than delayed, chemotherapy-induced nausea and vomiting (CINV).
8: A patient with metastatic colorectal cancer who is a known DPYD gene variant carrier (e.g., 13, c.1679T>G, DPYD2A) associated with significantly reduced dihydropyrimidine dehydrogenase (DPD) activity is scheduled to receive a fluoropyrimidine-based chemotherapy regimen. Which of the following interventions is most appropriate?
(a) Proceed with the standard dose of fluoropyrimidine as DPYD variant penetrance is low.
(b) Administer a test dose of 5-fluorouracil and monitor for acute toxicity.
(c) Empirically reduce the starting dose of the fluoropyrimidine by at least 50% or select an alternative non-fluoropyrimidine regimen if feasible, with careful toxicity monitoring.
(d) Co-administer uridine triacetate prophylactically with the standard fluoropyrimidine dose.
(e) Switch to capecitabine as it has a different DPD metabolism profile compared to 5-FU.
9: What is the primary pharmacological rationale for the significantly increased risk of severe and fatal immune-mediated toxicities when ipilimumab is dosed at 10 mg/kg versus 3 mg/kg in melanoma, despite only a modest improvement in efficacy at the higher dose for some indications?
(a) Saturation of CTLA-4 receptors on regulatory T cells (Tregs) occurs at 3 mg/kg, with higher doses predominantly affecting effector T cells.
(b) The 10 mg/kg dose leads to a more profound and sustained depletion of Tregs, shifting the immune balance further towards autoimmunity.
(c) Higher doses achieve greater penetration into immune-privileged sites like the CNS, triggering localized inflammatory responses.
(d) The pharmacokinetic profile at 10 mg/kg leads to non-linear accumulation and prolonged target engagement beyond what is necessary for anti-tumor effect.
(e) Increased Fc-gamma receptor binding at higher concentrations leads to enhanced antibody-dependent cell-mediated cytotoxicity (ADCC) against normal tissues expressing CTLA-4.
10: A patient with chronic lymphocytic leukemia (CLL) is being treated with venetoclax. They are also taking clarithromycin for a respiratory infection. Why is this combination particularly concerning and what is the recommended management?
(a) Clarithromycin induces CYP3A4, reducing venetoclax efficacy; venetoclax dose should be increased.
(b) Venetoclax is a strong P-glycoprotein inhibitor, increasing clarithromycin levels and QTc prolongation risk; monitor ECG closely.
(c) Clarithromycin is a strong CYP3A4 inhibitor, significantly increasing venetoclax exposure and risk of tumor lysis syndrome (TLS) and neutropenia; venetoclax dose reduction or interruption is critical.
(d) Both drugs compete for renal tubular secretion, increasing the risk of nephrotoxicity; ensure adequate hydration.
(e) Venetoclax can cause myelosuppression, which is exacerbated by clarithromycin's direct bone marrow toxicity; prophylactic G-CSF is indicated.
11: Sotorasib, a KRAS G12C inhibitor, has shown efficacy in NSCLC. Which of the following is a key pharmacological characteristic that can significantly impact its clinical use and necessitates specific patient counseling or management?
(a) Its potent induction of CYP2C9, requiring dose adjustments for co-administered substrates like warfarin.
(b) A high incidence of severe, irreversible cardiotoxicity, mandating baseline and regular cardiac function monitoring.
(c) Significant hepatotoxicity, which is often dose-dependent and requires frequent liver function tests, especially when co-administered with other hepatotoxic agents or CYP3A4 inhibitors.
(d) Its susceptibility to acid-reducing agents (e.g., PPIs, H2RAs), which can decrease its absorption and efficacy, requiring staggered administration or avoidance.
(e) A very long terminal half-life allowing for weekly dosing.
12: A patient receiving pembrolizumab for metastatic melanoma develops Grade 3 colitis (7 watery stools per day, abdominal pain, blood in stool). Initial management with high-dose corticosteroids (prednisolone ) for 5 days shows minimal improvement. What is the next most appropriate pharmacological intervention?
(a) Adding oral budesonide to the current corticosteroid regimen.
(b) Switching from intravenous methylprednisolone to oral prednisolone at an equivalent dose.
(c) Initiating infliximab or vedolizumab.
(d) Empirically starting broad-spectrum antibiotics covering enteric pathogens.
(e) Increasing the dose of prednisolone to 3 mg/kg/day.
13: A patient with estrogen receptor-positive, HER2-negative metastatic breast cancer is being treated with palbociclib and letrozole. The patient experiences recurrent Grade 3 neutropenia (ANC < ) leading to treatment delays, despite appropriate dose interruptions and reductions of palbociclib. Which statement best explains the mechanism of palbociclib-induced neutropenia and its typical clinical course?
(a) It is primarily due to direct cytotoxic effects on myeloid progenitor cells, leading to prolonged aplasia.
(b) It is a result of CDK4/6 inhibition causing G1 arrest in hematopoietic progenitor cells, is generally reversible, and rarely associated with febrile neutropenia.
(c) It is an immune-mediated destruction of mature neutrophils, often requiring immunosuppressive therapy.
(d) It is caused by inhibition of G-CSF receptor signaling, making G-CSF use ineffective.
(e) It is an idiosyncratic reaction unrelated to its primary mechanism of action.
14: When converting a patient from oral morphine to transdermal fentanyl for chronic cancer pain, which of the following principles is most crucial for ensuring safety and efficacy, particularly in an opioid-tolerant patient who is cachectic?
(a) An initial fentanyl patch strength should be conservatively chosen based on approximately a 100:1 oral morphine to transdermal fentanyl (mg/day: mcg/hr) ratio, with careful consideration of the patient's cachexia potentially affecting absorption.
(b) Fentanyl patches can be cut to titrate the dose more precisely in the initial conversion period.
(c) The full analgesic effect of the first fentanyl patch is achieved within 2-4 hours, allowing for rapid dose titration.
(d) If breakthrough pain occurs, the fentanyl patch dose should be immediately increased without waiting for the next scheduled change.
(e) Transdermal buprenorphine is a more suitable first-line option for conversion in cachectic patients due to better absorption.
15: Sacituzumab govitecan is an antibody-drug conjugate targeting Trop-2, with an SN-38 (active metabolite of irinotecan) payload. Patients homozygous for the UGT1A1*28 allele are at increased risk of which specific toxicities with this agent, mirroring those seen with irinotecan?
(a) Severe cardiotoxicity and infusion reactions.
(b) Profound myelosuppression (especially neutropenia) and severe diarrhea.
(c) Peripheral neuropathy and renal impairment.
(d) Hepatotoxicity and interstitial lung disease.
(e) Hand-foot syndrome and mucositis.
16: A patient with metastatic renal cell carcinoma is treated with cabozantinib. Which of the following adverse effects is most likely to be dose-limiting and requires proactive management due to its mechanism of inhibiting VEGFR, MET, and AXL?
(a) Hyperglycemia
(b) Palmar-plantar erythrodysesthesia (Hand-Foot Syndrome)
(c) Alopecia
(d) QTc prolongation
(e) Hypothyroidism
17: A patient with ER+/HER2- metastatic breast cancer is receiving ribociclib. Which baseline and ongoing monitoring is MOST critical specifically due to ribociclib's known potential for a serious, although uncommon, cardiac adverse event?
(a) Regular serum creatinine levels
(b) Baseline and serial electrocardiograms (ECGs) focusing on QTc interval
(c) Frequent liver function tests (LFTs) including bilirubin
(d) Complete blood counts with differential, focusing on neutrophils
(e) Thyroid function tests (TFTs)
18: What is the primary mechanism by which denosumab exerts its effects in preventing skeletal-related events in patients with bone metastases?
(a) Direct cytotoxic effect on osteoclasts
(b) Inhibition of osteoblast maturation
(c) Binding to and inhibiting RANK Ligand (RANKL)
(d) Promoting renal excretion of calcium
(e) Acting as a bisphosphonate analog integrating into bone matrix
19: A patient receiving bleomycin as part of their lymphoma regimen develops progressive dyspnea and a dry cough. A chest X-ray shows bilateral interstitial infiltrates. Which pharmacological characteristic of bleomycin is most relevant to this presentation?
(a) Its inactivation primarily by bleomycin hydrolase, levels of which are low in skin and lung tissue.
(b) Its propensity to cause severe myelosuppression.
(c) Its primary route of excretion being renal, requiring dose adjustment in kidney disease.
(d) Its known interaction with CYP3A4 inducers.
(e) Its ability to cause significant neurotoxicity.
20: Which of the following tyrosine kinase inhibitors used in chronic myeloid leukemia (CML) has a significant warning regarding the risk of arterial occlusive events, including cardiovascular, cerebrovascular, and peripheral vascular events?
(a) Imatinib
(b) Dasatinib
(c) Nilotinib
(d) Bosutinib
(e) Ponatinib
21: A patient with advanced melanoma is treated with a combination of nivolumab and relatlimab. What is the distinct immunological checkpoint target of relatlimab?
(a) CTLA-4
(b) PD-1
(c) PD-L1
(d) LAG-3
(e) TIM-3
22: What is the primary rationale for administering leucovorin (folinic acid) concurrently with pemetrexed?
(a) To enhance the cytotoxic effect of pemetrexed on tumor cells.
(b) To reduce the hematological and gastrointestinal toxicities of pemetrexed by replenishing reduced folate pools in normal cells.
(c) To prevent pemetrexed-induced nephrotoxicity.
(d) To act as a direct antidote in case of pemetrexed overdose.
(e) To improve the oral bioavailability of pemetrexed.
23: A patient experiences a severe infusion-related reaction to rituximab despite premedication. Management includes stopping the infusion and administering corticosteroids and antihistamines. If the decision is made to rechallenge, which modification to the rituximab administration is most appropriate?
(a) Administering a subcutaneous formulation instead.
(b) Increasing the premedication doses and restarting at a significantly slower infusion rate.
(c) Switching to ofatumumab as it has a lower risk of infusion reactions.
(d) Administering a test dose of rituximab diluted in a larger volume.
(e) Adding an NSAID to the premedication regimen.
24: Lutetium (177Lu) oxodotreotide (Lutathera) is used for treating somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs). What is the critical role of the co-administered amino acid solution?
(a) To enhance tumor uptake of the radiopharmaceutical.
(b) To reduce radiation-induced nausea and vomiting.
(c) To protect the kidneys from radiation damage by reducing proximal tubular reabsorption of the radiopharmaceutical.
(d) To improve the stability of the 177Lu-oxodotreotide complex.
(e) To stimulate somatostatin receptor expression.
25: Which of the following statements accurately describes a key pharmacological difference between dabrafenib (a BRAF inhibitor) and trametinib (a MEK inhibitor) when used in combination?
(a) Dabrafenib commonly causes pyrexia, while trametinib is more associated with skin rash and LVEF reduction.
(b) Both drugs are strong inhibitors of CYP3A4.
(c) Trametinib has a significantly longer half-life than dabrafenib, allowing for once-daily dosing.
(d) Resistance to dabrafenib monotherapy typically involves MEK pathway upregulation, which is overcome by trametinib.
(e) Dabrafenib is primarily renally excreted, whereas trametinib undergoes hepatic metabolism.
26: A patient develops symptomatic hypercalcemia of malignancy. After initial hydration, which agent provides the most rapid and potent inhibition of osteoclast-mediated bone resorption?
(a) Oral phosphorus supplementation
(b) Intravenous bisphosphonate (e.g., zoledronic acid)
(c) Subcutaneous calcitonin
(d) Intravenous gallium nitrate
(e) Oral cinacalcet
27: What is the most significant dose-limiting toxicity associated with high-dose cytarabine (HiDAC) regimens used in acute myeloid leukemia?
(a) Cardiotoxicity
(b) Cerebellar toxicity
(c) Severe mucositis
(d) Pulmonary fibrosis
(e) Renal failure
28: A patient is being treated with olaparib for metastatic ovarian cancer with a BRCA1 mutation. Which concomitant medication class should be used with extreme caution or avoided due to the potential for significantly increasing olaparib exposure and toxicity?
(a) Proton pump inhibitors
(b) HMG-CoA reductase inhibitors (statins)
(c) Potent CYP3A4 inhibitors (e.g., itraconazole, clarithromycin)
(d) Non-steroidal anti-inflammatory drugs (NSAIDs)
(e) Beta-blockers
29: Which of the following targeted therapies works by inhibiting the Bruton's tyrosine kinase (BTK) enzyme, playing a crucial role in B-cell signaling and survival?
(a) Venetoclax
(b) Idelalisib
(c) Ibrutinib
(d) Rituximab
(e) Lenalidomide
30: Prophylactic rasburicase is considered for a patient at high risk of tumor lysis syndrome (TLS). What is the primary mechanism of action of rasburicase in preventing or treating hyperuricemia associated with TLS?
(a) It inhibits xanthine oxidase, preventing the formation of uric acid.
(b) It promotes the renal excretion of uric acid.
(c) It is a recombinant urate oxidase that converts uric acid to allantoin, a more soluble metabolite.
(d) It alkalinizes the urine, increasing uric acid solubility.
(e) It chelates circulating uric acid, facilitating its removal.
31: A patient with metastatic castrate-resistant prostate cancer is receiving radium-223 dichloride. Which of the following best describes its mechanism of anti-tumor action?
(a) It is a beta-emitting isotope that causes diffuse bone marrow suppression.
(b) It is an alpha-emitting calcium mimetic that selectively targets bone metastases, inducing double-strand DNA breaks.
(c) It inhibits androgen receptor signaling in prostate cancer cells within the bone.
(d) It is a gamma-emitter that allows for external beam targeting of bone lesions.
(e) It stimulates an immune response against tumor cells in the bone microenvironment.
32: Which specific toxicity is uniquely associated with an increased risk in patients receiving checkpoint inhibitors (e.g., pembrolizumab) who have previously undergone allogeneic stem cell transplantation?
(a) Hypophysitis
(b) Severe colitis
(c) Exacerbation or new onset of graft-versus-host disease (GVHD)
(d) Pneumonitis
(e) Hepatitis
33: What is the primary pharmacological rationale for the use of dexrazoxane in patients receiving anthracycline-based chemotherapy?
(a) To enhance the cytotoxic efficacy of anthracyclines.
(b) To reduce the incidence and severity of anthracycline-induced cardiotoxicity by chelating iron.
(c) To prevent anthracycline extravasation.
(d) To alleviate anthracycline-induced nausea and vomiting.
(e) To reverse multidrug resistance to anthracyclines.
34: A patient taking lenvatinib for advanced thyroid cancer develops hypertension (BP 160/100 mmHg) despite being on one antihypertensive agent. According to typical management guidelines for TKI-induced hypertension, what is an appropriate next step?
(a) Immediately discontinue lenvatinib permanently.
(b) Add another antihypertensive agent from a different class and continue lenvatinib with close monitoring.
(c) Reduce the dose of lenvatinib by one level.
(d) Switch to a different TKI with a lower risk of hypertension.
(e) Hospitalize the patient for intravenous antihypertensive therapy.
35: Which of the following is a critical consideration regarding the drug interaction potential of midostaurin, a FLT3 inhibitor used in AML?
(a) It is a potent inducer of CYP2D6, reducing levels of co-administered substrates.
(b) It is primarily renally excreted, requiring dose adjustment in severe renal impairment.
(c) It is a substrate and inhibitor of CYP3A4; co-administration with strong CYP3A4 inhibitors or inducers requires dose modification or avoidance.
(d) It has minimal protein binding, leading to a large volume of distribution.
(e) It significantly prolongs the QTc interval independently of CYP interactions.
36: What is the primary molecular target of alpelisib, used in HR-positive, HER2-negative, PIK3CA-mutated advanced breast cancer?
(a) Mammalian target of rapamycin (mTOR)
(b) Epidermal growth factor receptor (EGFR)
(c) The alpha-specific catalytic subunit of phosphatidylinositol 3-kinase (PI3K$\alpha$)
(d) Vascular endothelial growth factor receptor (VEGFR)
(e) Fibroblast growth factor receptor (FGFR)
37: A patient develops Grade 2 pneumonitis (symptomatic, limiting instrumental ADLs) while on durvalumab. After holding durvalumab and initiating prednisone 1 mg/kg/day, symptoms improve within 72 hours. What is the most appropriate next step regarding durvalumab therapy once corticosteroids are tapered appropriately?
(a) Permanently discontinue durvalumab.
(b) Rechallenge with durvalumab at a reduced dose.
(c) Rechallenge with durvalumab at the same dose if corticosteroids are tapered off over at least 4 weeks and pneumonitis has resolved to Grade .
(d) Switch to a different checkpoint inhibitor like atezolizumab.
(e) Add prophylactic inhaled corticosteroids before resuming durvalumab.
38: Which statement most accurately describes the pharmacology of belzutifan, used for von Hippel-Lindau (VHL) disease-associated renal cell carcinoma?
(a) It is a potent VEGFR tyrosine kinase inhibitor.
(b) It inhibits hypoxia-inducible factor 2$\alpha$ (HIF-2$\alpha$).
(c) It is an antibody targeting carbonic anhydrase IX.
(d) It directly inhibits the mutated VHL protein.
(e) It is an mTOR pathway inhibitor.
39: A patient receiving long-term opioid therapy with morphine ER 60 mg twice daily for cancer pain is experiencing inadequate analgesia and wishes to switch to methadone. Which principle is paramount during this conversion?
(a) A direct milligram-to-milligram conversion ratio can be safely used.
(b) Methadone's long and variable half-life and incomplete cross-tolerance necessitate a very conservative starting dose (e.g., reducing the equianalgesic dose by 75-90%) and slow titration.
(c) Methadone primarily undergoes renal excretion, requiring dose adjustment in kidney disease.
(d) The switch can be completed within 24 hours by stopping morphine and starting the calculated equianalgesic dose of methadone.
(e) Methadone has no significant QTc prolongation risk.
40: What is the primary mechanism by which daratumumab exerts its therapeutic effect in multiple myeloma?
(a) Inhibition of proteasome activity leading to apoptosis.
(b) Binding to CD38 on myeloma cells, inducing antibody-dependent cellular cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC), and other immune-mediated mechanisms.
(c) Modulation of the bone marrow microenvironment by inhibiting angiogenesis.
(d) Acting as an immunomodulatory drug (IMiD) to enhance T-cell and NK-cell activity.
(e) Blocking signaling pathways critical for myeloma cell survival, such as NF-$\kappa$B.
Answers
1: (c) Adding a c-MET inhibitor such as capmatinib or tepotinib to osimertinib.
2: (d) Warfarin for atrial fibrillation.
3: (a) Prophylactic colestipol or budesonide initiated with neratinib.
4: (e) The risk of severe cutaneous adverse reactions (SCARs), including SJS/TEN, necessitates careful skin monitoring and patient education.
5: (c) Immunoassay-based methotrexate tests may show falsely elevated levels for several days due to DAMPA (a methotrexate metabolite acted upon by glucarpidase), requiring reliance on HPLC/LC-MS methods if available, or clinical judgment.
6: (b) The risk of profound and prolonged myelosuppression, particularly thrombocytopenia.
7: (b) Olanzapine provides broad antiemetic coverage primarily by antagonizing dopamine D2 and histamine H1 receptors, with lesser effects on 5-HT2A/C and 5-HT3 receptors.
8: (c) Empirically reduce the starting dose of the fluoropyrimidine by at least 50% or select an alternative non-fluoropyrimidine regimen if feasible, with careful toxicity monitoring.
9: (b) The dose leads to a more profound and sustained depletion or functional impairment of Tregs, shifting the immune balance further towards autoimmunity.
10: (c) Clarithromycin is a strong CYP3A4 inhibitor, significantly increasing venetoclax exposure and risk of tumor lysis syndrome (TLS) and neutropenia; venetoclax dose reduction or interruption is critical.
11: (d) Its susceptibility to acid-reducing agents (e.g., PPIs, H2RAs), which can decrease its absorption and efficacy, requiring staggered administration or avoidance.
12: (c) Initiating infliximab or vedolizumab.
13: (b) It is a result of CDK4/6 inhibition causing G1 arrest in hematopoietic progenitor cells, is generally reversible, and rarely associated with febrile neutropenia.
14: (a) An initial fentanyl patch strength should be conservatively chosen based on approximately a 100:1 oral morphine to transdermal fentanyl (mg/day: mcg/hr) ratio, with careful consideration of the patient's cachexia potentially affecting absorption.
15: (b) Profound myelosuppression (especially neutropenia) and severe diarrhea.
16: (b) Palmar-plantar erythrodysesthesia (Hand-Foot Syndrome)
17: (b) Baseline and serial electrocardiograms (ECGs) focusing on QTc interval
18: (c) Binding to and inhibiting RANK Ligand (RANKL)
19: (a) Its inactivation primarily by bleomycin hydrolase, levels of which are low in skin and lung tissue.
20: (e) Ponatinib
21: (d) LAG-3
22: (b) To reduce the hematological and gastrointestinal toxicities of pemetrexed by replenishing reduced folate pools in normal cells.
23: (b) Increasing the premedication doses and restarting at a significantly slower infusion rate.
24: (c) To protect the kidneys from radiation damage by reducing proximal tubular reabsorption of the radiopharmaceutical.
25: (a) Dabrafenib commonly causes pyrexia, while trametinib is more associated with skin rash and LVEF reduction.
26: (c) Subcutaneous calcitonin (Note: Bisphosphonates are more potent and durable but calcitonin is faster acting for initial rapid reduction)
27: (b) Cerebellar toxicity
28: (c) Potent CYP3A4 inhibitors (e.g., itraconazole, clarithromycin)
29: (c) Ibrutinib
30: (c) It is a recombinant urate oxidase that converts uric acid to allantoin, a more soluble metabolite.
31: (b) It is an alpha-emitting calcium mimetic that selectively targets bone metastases, inducing double-strand DNA breaks.
32: (c) Exacerbation or new onset of graft-versus-host disease (GVHD)
33: (b) To reduce the incidence and severity of anthracycline-induced cardiotoxicity by chelating iron.
34: (b) Add another antihypertensive agent from a different class and continue lenvatinib with close monitoring.
35: (c) It is a substrate and inhibitor of CYP3A4; co-administration with strong CYP3A4 inhibitors or inducers requires dose modification or avoidance.
36: (c) The alpha-specific catalytic subunit of phosphatidylinositol 3-kinase (PI3K$\alpha$)
37: (c) Rechallenge with durvalumab at the same dose if corticosteroids are tapered off over at least 4 weeks and pneumonitis has resolved to Grade . (Note: For Grade 2, rechallenge may be considered; for Grade 3/4, discontinuation is typical. Always refer to specific guidelines.)
38: (b) It inhibits hypoxia-inducible factor 2$\alpha$ (HIF-2$\alpha$).
39: (b) Methadone's long and variable half-life and incomplete cross-tolerance necessitate a very conservative starting dose (e.g., reducing the equianalgesic dose by 75-90%) and slow titration.
40: (b) Binding to CD38 on myeloma cells, inducing antibody-dependent cellular cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC), and other immune-mediated mechanisms.
