A 52-year-old woman comes to the office due to 2 weeks of constant back pain. She has also had several months of nonproductive cough, anorexia, and unintentional weight loss. The patient has a 40-pack-year smoking history. Physical examination shows diffuse muscle wasting, left lung crackles, and vertebral tenderness. Imaging reveals a left lung mass and lytic lesions in the vertebrae. Further evaluation confirms metastatic non-small cell lung cancer. Treatment with a cisplatin-based chemotherapy is begun, and the patient is also started on a neurokinin-1 receptor antagonist. The latter medication is most likely to improve which of the following in this patient?

Question

A 52-year-old woman comes to the office due to 2 weeks of constant back pain.  She has also had several months of nonproductive cough, anorexia, and unintentional weight loss.  The patient has a 40-pack-year smoking history.  Physical examination shows diffuse muscle wasting, left lung crackles, and vertebral tenderness.  Imaging reveals a left lung mass and lytic lesions in the vertebrae.  Further evaluation confirms metastatic non-small cell lung cancer.  Treatment with a cisplatin-based chemotherapy is begun, and the patient is also started on a neurokinin-1 receptor antagonist.  The latter medication is most likely to improve which of the following in this patient?

Quizplus · Accepted Answer

11ec160b_3be1_ae4b_9249_5366c9a2cef5_MD0001_00 Chemotherapy-induced nausea and vomiting (CINV) is a common side effect of cancer treatment. It is caused by both peripheral and central mechanisms, as follows: Acute-phase CINV (<24 hours after chemotherapy) is mediated primarily by the release of serotonin from intestinal enterochromaffin cells that have been damaged by chemotherapy. Serotonin stimulates vagal afferent fibers (5-HT3 receptors) in the bowel wall, which project to the brainstem and stimulate the vomiting reflex. Therefore, serotonin receptor antagonists (eg, ondansetron) can be used for treatment. Delayed-phase CINV (1-5 days after chemotherapy) is mediated primarily by increased levels of substance P in the brainstem due to chemotherapy-associated emetic stimuli in the cerebrospinal fluid and bloodstream. Substance P binds to and activates the neurokinin-1 (NK1) receptor in areas of the brainstem that mediate vomiting (eg, nucleus tractus solitarius, area postrema). Therefore, NK1 receptor antagonists (eg, aprepitant, fosaprepitant) are often used for treatment. Most patients who undergo chemotherapy associated with a high risk of vomiting (eg, cisplatin) receive a combination of serotonin receptor antagonists and NK1 receptor antagonists (often with other antiemetics) to prevent both types of CINV. (Choice B) Malignancy-related anorexia is the loss of muscle and fat caused by elevated levels of circulating inflammatory cytokines. Progesterone analogs (eg, megestrol acetate) are the first-line treatment; corticosteroids and cannabinoids are also frequently used. (Choice C) Malignancy-related hypercalcemia is typically treated with bisphosphonates (eg, zoledronic acid), which reduce osteoclast-mediated bone resorption. (Choice D) Opioid-induced constipation occurs due to opioid-mediated effects on the bowel wall, which reduce peristalsis. Methylnaltrexone, an opioid antagonist that has limited ability to cross the blood-brain barrier (it does not trigger withdrawal), can be used as treatment. (Choice E) Patients who have highly aggressive lymphomas and leukemias are at risk for tumor lysis syndrome (TLS) with chemotherapy. Its primary manifestation is renal damage from elevated uric acid levels (catabolism of nucleic acids released from tumor cells increases uric acid). Rasburicase, a drug that breaks down uric acid, is used to prevent TLS in high-risk patients. Educational objective: Chemotherapy-induced nausea and vomiting is mediated by peripheral and central mechanisms. It can be treated with serotonin receptor antagonists (eg, ondansetron) to prevent serotonin stimulation of afferent vagal fibers in the bowel wall (peripheral cause) and neurokinin-1 receptor antagonists (eg, aprepitant) to prevent the effects of substance P in the brainstem (central cause).

A 52-Year-Old Woman Comes to the Office Due to 2