Arokaris®

Neurokinin-1 receptor antagonists block the binding of substance P to the NK1 receptor; substance P has been shown to play a predominant role in CINV in the period from 24 hours up to 5 days post-chemotherapy (also known as the delayed phase). Fosnetupitant is the prodrug form of netupitant, and is dephosphorylated by plasma phosphatase to produce the active form.

Chemotherapy-induced nausea and vomiting (known as “CINV”) are common unpleasant and debilitating side effects of many cancer treatments⁵. CINV is one of the most feared side effects of chemotherapy for both patients and caregivers and, without adequate antiemetic prophylaxis, can occur in >90% of patients. The pathophysiology of CINV is a complex process that involves several molecules, such as neurotransmitters [serotonin (5-hydroxytryptamine or 5-HT₃), substance P (neurokinin-1), and dopamine] and their respective receptors in the central nervous system and the gastrointestinal tract, following activation by certain chemotherapy⁵. Consequences of uncontrolled CINV include dehydration and electrolyte imbalance, malnutrition, impaired daily functioning and quality of life, postponement or dose reduction of chemotherapy, and increased resource use and costs⁷. Patients tend to experience nausea more often than vomiting, and antiemetic medications (those intended to prevent, lessen or relieve CINV) are generally less effective in controlling nausea⁵.

Factors leading to the development of CINV can be related to the chemotherapy itself or to characteristics specific to the patient taking the anticancer drug. Historically, the risk of CINV was determined only by considering the emetogenic potential of the chemotherapy agent. A classification system details the emetogenicity of different chemotherapeutic agents and this has formed the basis for antiemetic treatment⁴. Highly emetogenic agents can cause CINV in >90% of patients without antiemetic prophylaxis; moderately emetogenic agents can cause CINV in 30–90% of patients; low emetogenic agents in 10–30% of patients; and minimally emetogenic agents have <10% risk of causing CINV without antiemetic prophylaxis. More recently, individual patient-related risk factors that may increase the chance of experiencing CINV have been identified. These include younger age, female gender, having had CINV previously, little or no previous alcohol use, being susceptible to motion sickness, having experienced morning sickness with pregnancy, anxiety/high pre-treatment expectation of nausea⁷.

Significant advances in this field have made the complete prevention of nausea and vomiting the goal of clinical management. A range of drugs are available for the management of CINV, with the choice of drugs guided by the type of chemotherapy agent(s) used and its ability to induce vomiting, along with patient-specific risk factors. The three key families of drugs used to prevent CINV are serotonin receptor antagonists (5-HT₃ RAs), which block the serotonin receptor, neurokinin-1 (NK-1) RAs, which block the NK-1 receptor, and corticosteroids⁵. Olanzapine, a potent antipsychotic that inhibits multiple receptors, is also a recent effective option. Antiemetic guidelines are available that advise prescribing clinicians on the optimal combinations of antiemetic agents^6,7.