Nausea and Vomiting in Cancer: It's Not Always the Chemotherapy

Substance P Antagonists (NK1-Receptor Antagonists)

Oral aprepitant, injectable fosaprepitant, and netupitant are some of the Substance P (NK1) antagonists used to treat nausea and vomiting. In a manner similar to 5-HT release, chemotherapeutic agents stimulate the cellular release of NK1 in the gut. This reaction in turn activates receptors in the vagus nerve and the chemotherapy trigger zone, which stimulates the vomiting center. The NK1 receptors are blocked by these agents. The main use of these medications has been to complement the 5-HT₃ antagonists for prophylaxis prior to administration of chemotherapy. Neurokinin-1receptor antagonists have not been studied in the setting of breakthrough nausea and vomiting but they are being used to treat delayed phase breakthrough CINV by the authors at their institution’s ED. The agents have been shown to be more effective than 5-HT₃ agents in preventing delayed phase nausea and vomiting.²⁵ As such, the possibility they may also be effective in treating delayed phase breakthrough CINV has led to this use. Recent studies have found these agents highly effective in the treatment of postoperative nausea and vomiting in high-risk patients.²⁶

The standard in recent years for prophylaxis has been combining 5-HT₃ antagonists, NK1 inhibitors, and dexamethasone. Netupitant/palonosetron (commonly referred to as NEPA) is a novel oral agent combining a long-acting 5-HT₃ antagonist, and a long-acting NK1 inhibitor for CINV prophylaxis.²⁷ Its use in treating delayed breakthrough vomiting remains to be seen.

Corticosteroids

Based on its antiemetic properties, the corticosteroid dexamethasone increases the effects of antiemetics (ie, metoclopramide and more recently 5-HT₃ and NK1 receptor antagonists) in preventing CINV, perhaps by reducing the blood-brain barrier permeability to emetogenic substances. There are also some evidence-based benefits in using dexamethasone in patients with bowel obstruction. It is also used to reduce ICP from cerebral edema.^{1,11,13,17,19}

Benzodiazepines

The benzodiazepines are best given to enhance the antiemetic effects of other drugs, especially in patients experiencing anxiety-related side effects. The benzodiazepines work well for anticipatory nausea. Lorazepam is the preferred drug of choice due to the lack of active metabolites. However, the clinician should always exercise caution when using benzodiazepines in elderly patients due to the increased risk of falls and cognitive impairment.^13,17,19

Cannabinoids

The observation that the incidence of CINV decreased in marijuana smokers led to the exploration of cannabinoids for the treatment of nausea and vomiting. Tetrahydrocannabinol, the psychoactive substance in marijuana, is a phytocannabinoid. Its receptor, CB1, exists throughout the brain. Synthetic cannabinoids such as oral dronabinol, oral nabilone, and intramuscular levonantradol have been used with antiemetic success superior to chlorpromazine, haloperidol, metoclopramide, and prochlorperazine, but at the cost of unpleasant CNS effects and postural hypotension in elderly patients.^1,13,17

As cited in a systematic review, cannabinoids appear to inhibit growth of glioblastoma multiforme, breast, prostate, and thyroid cancer, colon carcinoma, leukemia, and lymphomas. Cannabinoids can also benefit cancer patients by stimulating appetite, elevating mood, and inhibiting pain.²⁸ Clearly, more oncologic research needs to be done on the topic. As such, this class of medication is years, if not decades, away from use in the ED.

Nonpharmacologic Treatments

Acupuncture and Acupressure

A 2006 Cochrane systematic review and meta-analysis showed that acupuncture helped with acute CINV but not with delayed CINV.²⁹ Acupuncture was shown to work best with electro-acupuncture needles. Acupressure without needles helped nausea but not vomiting.²⁹ A more recent review on the specific P6 acupuncture area on the wrist near the median nerve found that electroacupuncture, but not manual acupuncture, was beneficial for first-day vomiting, and acupressure was effective for first-day nausea but not vomiting. Neither acupuncture nor acupressure was shown to help delayed nausea or vomiting.³⁰

Ginger

Ginger has been shown to help with CINV and anticipatory nausea, but not with other types of nausea.¹³ Supplementing routine antiemetics with 0.5 to 1.5 g of ginger per day for 6 days (beginning 3 days before chemotherapy) was shown to reduce the severity of nausea on the day of chemotherapy, but did not affect vomiting.²¹

Percutaneous Gastrostomy, Stenting, and Laser Therapy

Several strategies have been developed for palliation of intestinal obstruction when surgery is not warranted. Percutaneous gastrostomy tubes (PEG) are used to vent GI secretions that would otherwise build up. Esophageal, colorectal, and gastric outlet obstructions can be palliated by endoscopically placed stenting devices. Argon beam plasma coagulation laser therapy can be used for gastric outlet as well as colonic obstruction.^13,31 One review evaluating the benefits of colonic obstruction stenting found an 89% success rate in symptom relief. This same review noted that venting the PEG tube placement had an 84% rate of symptom relief.³¹