Dronabinol for Chemotherapy-induced Nausea and Vomiting Unresponsive to Antiemetics

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There are currently insufficient data to support the beneficial effects of dronabinol in the prevention of breakthrough chemotherapy-induced nausea and vomiting (CINV) in patients unresponsive to antiemetics, according to a review published in the journal Cancer Management and Research.

CINV is one of the most common symptoms feared by patients with cancer, but it may be prevented or lessened with antiemetic medications. Numerous antiemetic agents exist to manage CINV, including corticosteroids, 5HT3 receptor antagonists, and neurokinin receptor antagonists. Although those are the most frequently used, alternative drug classes, such as antihistamines, benzodiazepines, anticonvulsants, dopamine receptor antagonists, and cannabinoids, are also used in the prevention and management of CINV; however, these agents typically have lower efficacy and are associated with greater toxicity.

Dronabinol, a member of the cannabinoid class, contains a synthetic version of delta-9-THC, the active component of marijuana, making dronabinol an orally active cannabinoid. Despite current guidelines recommending dronabinol for the management of breakthrough CINV, there are limited data to support its routine use as an antiemetic in all chemotherapeutic regimens. Its unique adverse event profile of a "high" sensation and sedation may be preferable for patients who experience a major impact on quality of life, but it may not be as effective as 5HT3 receptor antagonists or neurokinin receptor antagonists in the prevention of CINV.

Cancer Management and Research
Cancer Management and Research

Abstract: Chemotherapy-induced nausea and vomiting (CINV) is one of the most common symptoms feared by patients, but may be prevented or lessened with appropriate medications. Several antiemetic options exist to manage CINV. Corticosteroids, serotonin receptor antagonists, and neurokinin receptor antagonists are the classes most commonly used in the prevention of CINV. There are many alternative drug classes utilized for the prevention and management of CINV such as antihistamines, benzodiazepines, anticonvulsants, cannabinoids, and dopamine receptor antagonists. Medications belonging to these classes generally have lower efficacy and are associated with more adverse effects. They are also not as well studied compared to the aforementioned agents. This review will focus on dronabinol, a member of the cannabinoid class, and its role in CINV. Cannabis sativa L. (also known as marijuana) contains naturally occurring delta-9-tetrahydrocannibinol (delta-9-THC). The synthetic version of delta-9-THC is the active ingredient in dronabinol that makes dronabinol an orally active cannabinoid. Evidence for clinical efficacy of dronabinol will be analyzed in this review as monotherapy, in combination with ondansetron, and in combination with prochlorperazine.

Keywords: dronabinol, cannabinoids, antiemetic, chemotherapy-induced nausea and vomiting  


Chemotherapy-induced nausea and vomiting (CINV) is one of the most common symptoms feared by patients, but may be prevented or lessened with appropriate medications.1 CINV is categorized as acute, delayed, anticipatory, breakthrough, or refractory.2 Acute-onset CINV may occur within a few minutes to several hours after treatment administration and typically resolves within the first 24 hours. Risk factors for the development of this kind of nausea include female sex, age <50 years, environment of administration, lack of history of chronic alcoholism, history of motion sickness, previous incidence of nausea and vomiting, emetogenicity of agent(s) administered, dose of emetogenic agent(s), infusion rate, duration of therapy, number of cycles, and efficacy of preventive antiemetic regimen. Delayed-onset CINV generally occurs in patients more than 24 hours after medication administration and may last 6–7 days. This type of nausea unfortunately tends to be more common, severe, and treatment resistant. Factors impacting the incidence of delayed CINV include dose and emetogenicity of chemotherapy agent(s), incidence of acute CINV, patient age, sex, and prophylactic antiemetics used. Anticipatory nausea and/or vomiting is considered a conditioned response and may occur after a negative prior experience with chemotherapy. This happens before a patient receives their next cycle of treatment. This type of CINV is more common in younger patients due to the aggressive nature of treatment. Breakthrough emesis is considered vomiting that occurs even with prophylactic treatment and/or requires the addition of “rescue” antiemetics. Refractory emesis is classified as vomiting that occurs with subsequent treatment when prophylactic antiemetics and/or rescue medications have been ineffective in previous cycles.

CINV may have a significant negative impact on a patient's quality of life (QoL) as well as lead to increased indirect and direct costs. When a patient's QoL is impacted in a negative manner, it may result in poor compliance with future treatment. The development of CINV has been reported to have a significant impact on QoL in 55%–60% of chemotherapy cycles administered to patients.1 The intensity of CINV and duration of CINV were the most notable factors linked to a more significant influence on QoL. In a study analyzing cost associated with the development of CINV, it was noted that the average cost was nearly $800 per patient for the first 5 days of the first cycle of chemotherapy.3 The cost analysis included overall direct and indirect costs: direct medical, missed work, productivity loss, and cost of any antiemetic medications taken on the day of treatment. Indirect costs were greater for patients with more severe CINV due to work absence for longer periods of time and reduced productivity. Additional undesirable effects of CINV to consider include metabolic imbalances, decline in self-care and functional ability, nutrient depletion, anorexia, worsening of the patient's performance status and mental status, wound dehiscence, esophageal tears, and withdrawal from potentially useful or curative treatment.2  

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