How Should Medications Be Initiated and Titrated to Reduce Acute and Delayed Nausea and Vomiting in the Setting of Chemotherapy?

Introduction and Scope of the Problem

Chemotherapy-induced nausea and vomiting (CINV) remains one of the most unpleasant, distressing, and feared symptoms for cancer patients. Without sufficient antiemetic prophylaxis, 30% to more than 90% of patients experience CINV with moderately emetogenic chemotherapy (MEC) or highly emetogenic chemotherapy (HEC) within the first 24 hours of administration. Moreover, 20% to 30% of patients may experience anticipatory nausea and vomiting. The incidence and severity vary based on the chemotherapeutic agent, dose, schedule, and concomitant therapies along with individual patient characteristics. When poorly controlled, CINV leads to electrolyte disturbances, dehydration, anorexia, weight loss, and diminished quality of life. Fear surrounding CINV may result in administration delays, dose reductions, or discontinuation of treatment altogether, mitigating the symptomatic control and life prolongation benefits resulting from antitumor therapy. The advent of 5-HT3 and NK ₁ antagonists that specifically target neuroreceptors implicated in CINV has dramatically improved the prevention and acute control of symptoms. However, delayed CINV remains difficult to control and poses a substantial burden for patients.

Relevant Pathophysiology

Chemotherapy is postulated to induce nausea and vomiting through several neurophysiological pathways. The most common mechanism is direct stimulation of the chemoreceptor trigger zone within the area postrema of the brain, which can be reached by emetogenic chemicals via blood or cerebrospinal fluid. Activation of receptors in the area postrema leads to stimulation of the vomiting center, resulting in nausea and emesis. Other mechanisms implicated in CINV include activation of peripheral pathways through stimulation of receptors within the gastrointestinal mucosa, the cortical pathway (psychogenic causes or abnormal tastes and smells), and the vestibular apparatus. Neurotransmitters such as dopamine, serotonin, histamine, vasopressin, and substance P, located within central and peripheral pathways, induce emesis when binding to their corresponding receptors. The current strategy in the management of CINV is to target multiple implicated receptors simultaneously to achieve optimal symptom control.

The symptom timeline categorizes CINV as anticipatory, acute, or delayed. Table 19.1 describes the time frame for each category and recognized risk factors. Symptom timing represents an important determinant in treatment strategies.

Summary of Evidence Regarding Treatment Recommendations

The prophylactic use of antiemetics has dramatically reduced the frequency of CINV. For example, in patients who receive cisplatin, a highly emetogenic agent, CINV has decreased in prevalence from almost 100% to 25% or less. Based on the success of this strategy, the American Society of Clinical Oncology (ASCO), National Comprehensive Cancer Network (NCCN), and Multinational Association of Supportive Care in Cancer (MASCC) published clinical practice guidelines on antiemetic choice based on emetic risk (ASCO and NCCN guidelines reported in Tables 19.2 and 19.3 ). Given that evidence-based tools to assess emetic risk for an individual patient are still not widely used, it is recommended that providers evaluate the emetic potential of each regimen and target medium-risk and high-risk agents for prevention. Several patient-related factors are also known to increase the risk for CINV (see Table 19.1 ); however, the role of these factors in the selection of antiemetic prophylaxis remains limited.