A systematic review of the treatment of nausea and/or vomiting in cancer unrelated to chemotherapy or radiation

Context: A systematic review of antiemetics for emesis in cancer unrelated to chemotherapy and radiation is an important step in establishing treatment recommendations and guiding future research. Therefore, a systematic review based on the question "What is the evidence that supports antiemetic choices in advanced cancer?" guided this review.

Objectives: To determine the level of evidence for antiemtrics in the management of nausea and vomiting in advanced cancer unrelated to chemotherapy and radiation, and to discover gaps in the evidence, which would provide important areas for future research.

Methods: Three databases and independent searches using different MeSH terms were performed. Related links were searched and hand searches of related articles were made. Eligible studies included randomized controlled trials (RCTs), prospective single-drug studies, studies that used guidelines based on the etiology of emesis, cohort studies, retrospective studies, and case series or single-patient reports. Studies that involved treatment of chemotherapy, radiation, or postoperation-related emesis were excluded. Studies that involved the treatment of emesis related to bowel obstruction were included. The strength of evidence was graded as follows: 1) RCTs, A; 2) single-drug prospective studies, B1; 3) studies based on multiple drug choices for etiology of emesis, B2; and 4) cohort, case series, retrospective, and single-patient reports, E. Level of evidence was determined by the Oxford Centre for Evidence-Based Medicine Levels of Evidence (May 2001) (A, B, C, D).

Results: Ninety-three articles were found. Fourteen were RCTs, most of them of low quality, based either on lack of blinding, lack of description of the method of randomization, concealment, and/or attrition. Metoclopramide had modest evidence (B) based on RCTs and prospective cohort studies. Octreotide, dexamethasone, and hyoscine butylbromide are effective in reducing symptoms of bowel obstruction, based on prospective studies and/or one RCT. There was no evidence that either multiple antiemetics or antiemetic choices based on the etiology of emesis were any better than a single antiemetic. There is poor evidence for dose response, intraclass or interclass drug switch, or antiemetic combinations in those individuals failing to respond to the initial antiemetic.

Conclusion: There are discrepancies between antiemetic studies and published antiemetic guidelines, which are largely based on expert opinion. Antiemetic recommendations have moderate to weak evidence at best. Prospective randomized trials of single antiemetics are needed to properly establish evidence-based guidelines.