Review Question - QID 109647

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Antimetabolites 5-Fluorouracil (5-FU) Toxicity QID: 109647 (M1.ON.17.4867)

QID 109647 (Type "109647" in App Search)

A 65-year-old G4P4 woman presents to her primary care physician complaining of a breast lump. She reports that she felt the lump while conducting a breast self-examination. Her past medical history is notable for endometrial cancer status post radical hysterectomy. She takes aspirin and fish oil. The patient drinks 3-4 alcoholic beverages per day and has a distant smoking history. Her temperature is 98.6°F (37°C), blood pressure is 130/75 mmHg, pulse is 90/min, and respirations are 18/min. A firm palpable mass in the upper outer quadrant of the right breast is noted on physical exam. Further workup reveals invasive ductal adenocarcinoma. She eventually undergoes radical resection and is started on a medication that is known to inhibit thymidylate synthetase. This patient is at increased risk for which of the following medication adverse effects?

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Peripheral neuropathy

25%

73/290

Pulmonary fibrosis

19%

55/290

Dilated cardiomyopathy

16/290

Ototoxicity

21/290

Photosensitivity

36%

104/290

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This patient is taking 5-fluorouracil, a pyrimidine analog that inhibits thymidylate synthase to decrease the production of dTMP. A key toxicity of 5-FU is photosensitivity.

5-FU is a pyrimidine analog which is activated to 5F-dUMP that forms a complex with folic acid. This complex inhibits thymidylate synthase, the enzyme that normally catalyzes the conversion of dUMP to dTMP. The resulting decrease in dTMP production leads to an inability for malignant cells to produce sufficient DNA and protein for normal replication.

Incorrect Answers:
Answer 1: Peripheral neuropathy is an adverse effect of vincristine, a microtubule inhibitor.

Answer 2: Pulmonary fibrosis is an adverse effect of bleomycin and busulfan.

Answer 3: Dilated cardiomyopathy is an adverse effect of trastuzumab (anti-HER2 monoclonal antibody) and the chemotherapeutic DNA intercalating agents, doxorubicin (adriamycin) and daunorubicin.

Answer 4: Ototoxicity is an adverse effect of platinum-based chemotherapeutic crosslinking agents (cisplatin and carboplatin)

Bullet Summary:
Photosensitivity and myelosuppression are two key adverse effects of 5-fluorouracil.

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