Clinical Pharmacology and Cancer Therapeutics
Utkarsh H. Acharya, DO, FACP
Tejaswini Dhawale, MD
A patient with stage III colorectal cancer is placed on adjuvant capecitabine and oxaliplatin with a creatinine clearance of 45 mL/min.
What is the most appropriate approach to dose reduction of capecitabine and/or oxaliplatin given this patient’s impaired renal function?
View Answer
Capecitabine is renally eliminated and should be reduced by 25% in this patient with a GFR between 30 and 50.
Capecitabine dose adjustments are as follows: CrCr >51, No dose adjustments; CrCl 30% to 50%, 25% dose reduction; contraindicated for Cr < 30
Oxaliplatin does not require dose reduction despite being eliminated by the kidneys when CrCl > 30 mL/min.
Suggested Readings:
Abraham J, Gulley JL. The Bethesda Handbook of Clinical Oncology. 5th ed. Wolters Kluwer; 2018.
DeVita VT, Rosenberg SA, Lawrence SL. DeVita, Hellman, and Rosenberg’s Cancer: Principles & Practice of Oncology. 11th ed. Wolters Kluwer; 2018.
Match the appropriate therapy option(s) with its corresponding clinical scenario(s).
A. Regorafenib
B. Carboplatin ×1 to 2 cycles
C. Cabozantinib
D. Nivolumab
E. Nelarabine
F. Inotuzumab ozogamicin
G. Osimertinib
H. Alectinib
1. Second-line option in a metastatic hepatocellular cancer patient who failed sorafenib ___.
2. Patient with stage I nonseminoma post orchiectomy who opts for further treatment while deferring clinically appropriate observation or radiation in further management ___.
3. Metastatic renal cell carcinoma patient seeking second-line option with survival benefit after failure of prior VEGF-directed therapy ___.
4. Patient with metastatic gastrointestinal stromal tumor who progressed after imatinib and sunitinib ___.
5. Patient with relapsed/refractory T-cell acute lymphoblastic leukemia ___.
6. Patient with relapsed/refractory B-cell acute lymphoblastic leukemia ___.
7. ALK-rearranged metastatic lung adenocarcinoma patient after failure of crizotinib and brain metastasis ___.
8. Metastatic non-small cell lung cancer patient harboring EGFR T790 point mutation after failure of earlier generation tyrosine kinase inhibitor (erlotinib, gefitinib, afatinib) ___.
View Answer
Match the appropriate therapy option(s) with its corresponding clinical scenario(s).
A. Regorafenib
B. Carboplatin ×1 to 2 cycles
C. Cabozantinib
D. Nivolumab
E. Nelarabine
F. Inotuzumab ozogamicin
G. Osimertinib
H. Alectinib
1. Second-line option in a metastatic hepatocellular cancer patient who failed sorafenib A, D.
2. Patient with stage I nonseminoma post orchiectomy who opts for further treatment while deferring clinically appropriate observation or radiation in further management B.
3. Metastatic renal cell carcinoma patient seeking second-line option with survival benefit after failure of prior VEGF-directed therapy C and D.
4. Patient with metastatic gastrointestinal stromal tumor who progressed after imatinib and sunitinib A.
5. Patient with relapsed/refractory T-cell acute lymphoblastic leukemia E.
6. Patient with relapsed/refractory B-cell acute lymphoblastic leukemia F.
7. ALK-rearranged metastatic lung adenocarcinoma patient after failure of crizotinib and brain metastasis H.
8. Metastatic non-small cell lung cancer patient harboring EGFR T790 point mutation after failure of earlier generation tyrosine kinase inhibitor (erlotinib, gefitinib, afatinib) G.
Suggested Readings: Abraham J, Gulley JL. The Bethesda Handbook of Clinical Oncology. 5th ed. Wolters Kluwer; 2018 and DeVita VT, Rosenberg SA, Lawrence SL. DeVita, Hellman, and Rosenberg’s Cancer: Principles & Practice of Oncology. 11th ed. Wolters Kluwer; 2018.
A patient with metastatic cholangiocarcinoma is noted to exhibit nonneutropenic fevers and negative infectious workup 3 days after receiving cycle 1 of gemcitabine and cisplatin.
What is the most likely explanation of his fevers if infection is ruled out?
View Answer
Gemcitabine may account for chemotherapy-induced fevers and should be considered in the absence of an infectious etiology.
Docetaxel is also implicated in chemotherapy-induced fevers.
Suggested Readings:
Abraham J, Gulley JL. The Bethesda Handbook of Clinical Oncology. 5th ed. Wolters Kluwer; 2018.
DeVita VT, Rosenberg SA, Lawrence SL. DeVita, Hellman, and Rosenberg’s Cancer: Principles & Practice of Oncology. 11th ed. Wolters Kluwer; 2018.
Match the cancer therapeutic agent with its predominant mechanism of excretion.
A. Renal
B. Hepatic
C. Both
Capecitabine __ Pemetrexed __ Cyclophosphamide __ Gemcitabine __
Topotecan __ Bleomycin __ Cisplatin __ Daunorubicin __ Lenalidomide __
Etoposide __ Fludarabine __ Melphalan __ Irinotecan __ Taxanes __
View Answer
Many chemotherapeutics undergo renal and/or hepatic metabolism with clearance. Special attention to renal and hepatic function should guide therapy dosing.
A. Renal
B. Hepatic
C. Both
Capecitabine A Pemetrexed A Cyclophosphamide A Gemcitabine A
Topotecan A Bleomycin A Cisplatin A Daunorubicin C Lenalidomide A
Etoposide B Fludarabine A Melphalan A Irinotecan C Taxanes B
Suggested Readings:
Abraham J, Gulley JL. The Bethesda Handbook of Clinical Oncology. 5th ed. Wolters Kluwer; 2018.
DeVita VT, Rosenberg SA, Lawrence SL. DeVita, Hellman, and Rosenberg’s Cancer: Principles & Practice of Oncology. 11th ed. Wolters Kluwer; 2018.
A patient with extensive stage Hodgkin disease is being treated with ABVD (Adriamycin, bleomycin, vinblastine, and dacarbazine). He returns after receiving one cycle of chemotherapy with plans for day 1 of cycle 2 with an absolute neutrophil count of 100 without fevers.
What is the best course of management?
View Answer
Continue chemotherapy—Neutropenia is not a contraindication to commencing with chemotherapy in Hodgkin lymphoma.
Suggested Readings:
Abraham J, Gulley JL. The Bethesda Handbook of Clinical Oncology. 5th ed. Wolters Kluwer; 2018.
DeVita VT, Rosenberg SA, Lawrence SL. DeVita, Hellman, and Rosenberg’s Cancer: Principles & Practice of Oncology. 11th ed. Wolters Kluwer; 2018.
Patient with metastatic lung adenocarcinoma is placed on pemetrexed maintenance.
What is the most appropriate supportive care measure to mitigate toxicity for this patient?
View Answer
Patients receiving pemetrexed therapy should receive corticosteroids during the first 3 days of therapy to reduce risk of skin rash along with vitamin B12 and folate supplementation throughout treatment to reduce toxicity.
Suggested Readings:
Abraham J, Gulley JL. The Bethesda Handbook of Clinical Oncology. 5th ed. Wolters Kluwer; 2018.
DeVita VT, Rosenberg SA, Lawrence SL. DeVita, Hellman, and Rosenberg’s Cancer: Principles & Practice of Oncology. 11th ed. Wolters Kluwer; 2018.
A 67-year-old patient with newly diagnosed diffuse large B-cell lymphoma is anticipating receiving induction chemotherapy with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone). Pretreatment evaluation reveals an ejection fraction of 34%.
Which therapeutic agent should be avoided in this scenario?
View Answer
Anthracyclines, such as doxorubicin, should be avoided in patients with low ejection fraction given the risk for cardiotoxicity.
Risks for anthracycline-induced cardiomyopathy include cumulative doses of anthracyclines, older age, preexisting cardiac disease, hypertension, mediastinal radiation, multiagent chemotherapy, poor nutritional status, prior anthracycline exposure, and diabetes mellitus.
Suggested Readings:
Abraham J, Gulley JL. The Bethesda Handbook of Clinical Oncology. 5th ed. Wolters Kluwer; 2018.
DeVita VT, Rosenberg SA, Lawrence SL. DeVita, Hellman, and Rosenberg’s Cancer: Principles & Practice of Oncology. 11th ed. Wolters Kluwer; 2018.
A patient receiving high-dose methotrexate (MTX) for CNS lymphoma is undergoing medication reconciliation at the time of hospitalization.
Which medications are known to inhibit the renal excretion of MTX and to be avoided while receiving this chemotherapy?
View Answer
NSAIDs, aspirin, cephalosporins, penicillin, proton-pump inhibitors, and probenecid should be avoided in patients receiving methotrexate as they can delay drug clearance and accentuate methotrexate toxicity.
Patients anticipating high-dose MTX with effusions/ascites should undergo fluid evacuation prior to administration of drug due to concerns for delayed clearance.
Suggested Readings:
Abraham J, Gulley JL. The Bethesda Handbook of Clinical Oncology. 5th ed. Wolters Kluwer; 2018.
DeVita VT, Rosenberg SA, Lawrence SL. DeVita, Hellman, and Rosenberg’s Cancer: Principles & Practice of Oncology. 11th ed. Wolters Kluwer; 2018.
A patient with primary CNS lymphoma is hospitalized for high-dose methotrexate at 5 g/m2.
What is the target urine pH that should be maintained and targeted safe level of MTX prior to discontinuing leucovorin rescue?
View Answer
Target urine pH with high-dose methotrexate: Intravenous hydration and urine alkalization to a pH > 7 are necessary to prevent precipitation of methotrexate in renal tissue and ensuing nephrotoxicity.
Target MTX levels prior to discontinuing leucovorin: Leucovorin, a folic acid analogue, is administered until MTX levels < 0.05 to 0.1 µM to mitigate systemic toxicity.
Suggested Readings:
Abraham J, Gulley JL. The Bethesda Handbook of Clinical Oncology. 5th ed. Wolters Kluwer; 2018.
DeVita VT, Rosenberg SA, Lawrence SL. DeVita, Hellman, and Rosenberg’s Cancer: Principles & Practice of Oncology. 11th ed. Wolters Kluwer; 2018.
A patient with newly diagnosed chronic-phase chronic myeloid leukemia (CML) is placed on a tyrosine kinase inhibitor (TKI). One week after, patient notes exertional dyspnea and a nonproductive cough. A chest x-ray reveals bilateral pleural effusions.
Which TKI is most implicated given this scenario?
View Answer
Dasatinib toxicity should be considered in a patient receiving drug with pulmonary complaints.
While multiple tyrosine kinase inhibitors are approved for CML, dasatinib is characteristically associated with pulmonary toxicity by way of pleural effusions and pulmonary hypertension.
Suggested Readings:
Abraham J, Gulley JL. The Bethesda Handbook of Clinical Oncology. 5th ed. Wolters Kluwer; 2018.
DeVita VT, Rosenberg SA, Lawrence SL. DeVita, Hellman, and Rosenberg’s Cancer: Principles & Practice of Oncology. 11th ed. Wolters Kluwer; 2018.
A 68-year-old man with stage IV diffuse large B-cell lymphoma is receiving rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) with interval scans demonstrating florid disease progression.
What is a plausible mechanism of chemotherapeutic drug resistance in this patient?
View Answer
Patients with a multidrug resistance phenotype is modulated by function of P-glycoprotein which results in increased drug efflux and reduced intracellular drug concentration resulting in treatment failure.
This mechanism of resistance has been observed for anthracyclines, vinca alkaloids, taxanes, and camptothecins (irinotecan/topotecan).
Suggested Readings:
Abraham J, Gulley JL. The Bethesda Handbook of Clinical Oncology. 5th ed. Wolters Kluwer; 2018.
DeVita VT, Rosenberg SA, Lawrence SL. DeVita, Hellman, and Rosenberg’s Cancer: Principles & Practice of Oncology. 11th ed. Wolters Kluwer; 2018.
A 74-year-old man with T-cell prolymphocytic leukemia is treated with the monoclonal antibody, alemtuzumab.
What infectious complication(s) are associated with this drug?
View Answer
Alemtuzumab is associated with the development of opportunistic infections including PJP, invasive aspergillosis, candidiasis, disseminated varicella-zoster virus infection, mycobacterial infection, and cytomegalovirus (CMV) infection.
Alemtuzumab is a humanized monoclonal antibody targeting CD52 and has a propensity for profound lymphopenia increasing the risk for opportunistic infections.
Patients should be placed on anti-infective prophylaxis while receiving this agent.
Suggested Readings:
Abraham J, Gulley JL. The Bethesda Handbook of Clinical Oncology. 5th ed. Wolters Kluwer; 2018.
DeVita VT, Rosenberg SA, Lawrence SL. DeVita, Hellman, and Rosenberg’s Cancer: Principles & Practice of Oncology. 11th ed. Wolters Kluwer; 2018.
A patient on 5-fluoruracil (5-FU), oxaliplatin, and leucovorin presents with severe diarrhea, vomiting, neutropenia, and severe mucositis 1 week after her second cycle of adjuvant chemotherapy for stage III colon cancer.
What is the most likely explanation for her presenting complaints?
View Answer
Dihydropyrimidine dehydrogenase (DPD) deficiency is a rare phenomenon (resulting from a mutation of the DPYD gene) and resulting in 5-FU toxicity.
DPD deficiency results in impaired catabolism of 5-FU and accentuate drug toxicity including severe GI, mucositis, and myelosuppression.
Suggested Readings:
Abraham J, Gulley JL. The Bethesda Handbook of Clinical Oncology. 5th ed. Wolters Kluwer; 2018.
DeVita VT, Rosenberg SA, Lawrence SL. DeVita, Hellman, and Rosenberg’s Cancer: Principles & Practice of Oncology. 11th ed. Wolters Kluwer; 2018.
Match the following agents with their respective class/mechanism of action.
A. Topoisomerase inhibitor
B. Microtubule inhibitor
C. Alkylator
D. Antimetabolite
Paclitaxel __ Vinblastine __ Cyclophosphamide __ Vincristine __ Etoposide __
Estramustine __ Topotecan __ Bendamustine __ Irinotecan __ Cisplatin __
Pemetrexed __ Docetaxel __ Eribulin ___ Nelarabine __ Eribulin __ Methotrexate __
View Answer
Match the following agents with their respective class/mechanism of action.
Indications for various cancers may be class specific as well as their respective toxicities and, thus, are important to identify.
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