Chemotherapy-Induced Nausea and Vomiting (CINV)

Despite surgical and medical advances in oncology, cytotoxic chemotherapy and radiation are still important frontline treatments for cancer. These treatments kill both cancer cells and healthy cells, resulting in extremely unpleasant and dangerous side-effects. One of the most immediate and distressing side-effects associated with chemotherapy and radiation in up to three fourths of all cancer patients is profound nausea and vomiting (Schwartzberg, 2007). Some chemotherapeutic agents are especially prone to causing emesis (in >90% of patients), especially drugs such as cisplatin, cyclophosphamide, and streptozocin (Schwartzberg, 2007). These adverse effects negatively impact patient quality of life and daily functioning, causing anorexia, weight loss, and often noncompliance to further therapy, which can lead to poorer treatment outcomes (Schwartzberg, 2007). The prophylaxis of CINV includes the prescription of one or more of the following list of anti-nausea drugs during the initiation of chemotherapy: corticosteroids, dopamine receptor antagonists, serotonin receptor antagonists, and neurokinin-1 receptor antagonists (Schwartzberg, 2007). These drugs have been shown to effectively eliminate the onset of CINV in a significant percentage of cancer patients in clinical trials for both acute (occurring up to 24 hours after treatment begins) and delayed (occurring from 24 hours and up to 120 hours after treatment begins) onsets of CINV (Schwartzberg, 2007). Despite these results, 12% to more than 50% of patients still develop some or all of the symptoms of CINV, with general nausea and the delayed onset of CINV being the most difficult symptoms to control (Schwartzberg, 2007; Vanscoy et al., 2005; Lachaine et al., 2005; Slatkin, 2007). When breakthrough nausea and/or emesis occur, rescue medications, and often outpatient and hospital visits are needed to alleviate these distressing symptoms (Schwartzberg, 2007). The cost to health care in Canada for ineffective pharmaceutical management of CINV has been estimated to be $591.72 CDN per patient (Lachaine et al., 2005). There remains a need for better management for CINV.

There is substantial evidence to indicate that cannabinoids, when taken orally or inhaled, can be effective to treat both the nausea and vomiting associated with chemotherapy. Cannabinoids have shown to be especially effective in treating nausea, a side-effect that is the least well-treated by the current line-up of antiemetics despite being the most distressing to patients (de Boer-Dennert et al., 1997; Slatkin, 2007; Schwartzberg, 2007). Some of the clinical trials indicating the effectiveness of cannabinoids in treating CINV include:

1) Tramer et al. (2001) conducted a systematic review of 30 randomized studies involving a total of 1366 patients. The efficacy and toxicity of cannabinoid drugs were compared to placebo or other antiemetics for the treatment of acute CINV. The cannabinoids used in the studies were either oral dronabinol, oral nabilone (a synthetic form of dronabinol), or intramuscular levonantradol (a synthetic form of dronabinol). A quantitative analysis of the data found that cannabinoids were statistically more effective in controlling chemotherapy related sickness than conventional antiemetics. The analysis also revealed that patients showed a preference for cannabinoid-based therapy over conventional antiemetics for future chemotherapy cycles, although the incidence of side effects associated with cannabinoids was higher.

2) In a small study comparing dronabinol with ondansetron, a serotonin receptor antagonist, in patients receiving highly or moderately emetogenic chemotherapy, dronabinol exhibited the greatest efficacy in preventing and reducing nausea (Meiri et al., 2005). Rates of the absence of nausea were 71% with dronabinol, 64% with odansetron, and 15% with placebo. The severity of the nausea experienced by the dronabinol group was also rated as being less than half of the severity of the nausea experienced in the ondansetron group.

3) Orr and McKernan (1981) conducted a randomized, double-blinded trial in 55 chemotherapy patients with severe nausea. Oral dronabinol was found to be more efficacious than prochlorperazine in controlling nausea and emesis in this study. 72.7% of patients were nausea-free with dronabinol versus 14.5% of patients on prochlorperazine and 9% of patients on placebo.

4) Einhorn et al. (1981) conducted a randomized, double-blinded clinical trial in 80 chemotherapy patients on cisplatin, a highly emetogenic chemotherapeutic agent, and found that nabilone (synthetic dronabinol) was significantly more effective than prochlorperazine in reducing the frequency of emesis and the severity of nausea for both acute and delayed CINV. Nabilone was preferred by 75% of patients, despite the fact that lethargy and hypotension were more pronounced with nabilone treatment. Similar results were found by Niriranen and Mattson (1985) in a trial with 24 lung cancer patients. For these reasons, Cannasat is developing Relivar as a novel pharmaceutical agent to treat chemotherapy-induced nausea and vomiting. Relivar is essentially a reformulation of oral dronabinol, with the aim of improved efficacy and a superior adverse events profile.

For these reasons, Cynapsus is developing Relivar as a novel pharmaceutical agent to treat chemotherapy-induced nausea and vomiting. Relivar is essentially a reformulation of oral dronabinol, with the aim of improved efficacy and a superior adverse events profile.

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