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Chapter 54: Cancer Chemotherapy

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.

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

(A) Cross-linking of double-stranded DNA

(B) Inhibition of DNA-dependent RNA synthesis

(C) Interference with the activity of topoisomerases I

(D) Irreversible inhibition of thymidylate synthase

(E) Selective inhibition of DNA polymerases

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.

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.

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

(A) Cyclophosphamide

(B) Doxorubicin

(C) Fluorouracil

(D) Methotrexate

(E) Tamoxifen

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.

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.

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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