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Chapter 54: Cancer Chemotherapy

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A 32-year-old woman underwent segmental mastectomy for a breast tumor of 3 cm diameter. Lymph node sampling revealed 2 involved nodes. Because chemotherapy is of established value in her situation, she underwent postoperative treatment with antineoplastic drugs. The regimen consisted of doxorubicin followed by cyclophosphamide/methotrexate/fluorouracil. Adjunctive drugs included tamoxifen because the tumor cells were hormone receptor-positive.

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Which of the following best describes the mechanism of anticancer action of cellular metabolites of fluorouracil?

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(A) Cross-linking of double-stranded DNA

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(B) Inhibition of DNA-dependent RNA synthesis

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(C) Interference with the activity of topoisomerases I

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(D) Irreversible inhibition of thymidylate synthase

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(E) Selective inhibition of DNA polymerases

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Fluorouracil (5-FU) undergoes metabolism to form 5-fluoro-2′-deoxyuridine 5′-phosphate (5-dUMP). This metabolite forms a covalently bound ternary complex with thymidylate synthase and its coenzyme N-methylenetetrahydrofolate. The synthesis of thymine nucleotides is blocked, DNA synthesis is inhibited, and a “thymineless death” of cells results. The answer is D.

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A 32-year-old woman underwent segmental mastectomy for a breast tumor of 3 cm diameter. Lymph node sampling revealed 2 involved nodes. Because chemotherapy is of established value in her situation, she underwent postoperative treatment with antineoplastic drugs. The regimen consisted of doxorubicin followed by cyclophosphamide/methotrexate/fluorouracil. Adjunctive drugs included tamoxifen because the tumor cells were hormone receptor-positive.

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The chemotherapy undertaken by this patient caused acute hemorrhagic cystitis. Which drug was most likely to be responsible for this toxicity?

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(A) Cyclophosphamide

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(B) Doxorubicin

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(C) Fluorouracil

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(D) Methotrexate

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(E) Tamoxifen

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Acrolein, a toxic metabolite of cyclophosphamide that is concentrated in the urine, is associated with hemorrhagic cystitis. Mesna, a sulfur-containing substance that also concentrates in urine, can be administered in an attempt to prevent this complication. The answer is A.

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A 32-year-old woman underwent segmental mastectomy for a breast tumor of 3 cm diameter. Lymph node sampling revealed 2 involved nodes. Because chemotherapy is of established value in her situation, she underwent postoperative treatment with antineoplastic drugs. The regimen consisted of doxorubicin followed by cyclophosphamide/methotrexate/fluorouracil. Adjunctive drugs included tamoxifen because the tumor cells were hormone receptor-positive.

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After several cycles of chemotherapy, the patient was found to have a high resting pulse rate. A noninvasive radionuclide scan revealed evidence of cardiomyopathy. The drug that is most likely responsible for the cardiac toxicity is

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