Ryan, J.L., Heckler, C.E., Roscoe, J.A., Dakhil, S.R., Kirshner, J., Flynn, P.J., … Morrow, G.R. (2012). Ginger (Zingiber officinale) reduces acute chemotherapy-induced nausea: A URCC CCOP study of 576 patients. Supportive Care in Cancer, 20, 1479-1489.

To determine the dose and efficacy of ginger at reducing the severity of chemotherapy-induced nausea (CIN) on day one of chemotherapy

Patients were randomly assigned to four arms.

• Placebo
• 0.5 g ginger
• 1.0 g ginger
• 1.5 g ginger

Nausea occurrence and severity were assessed at a baseline cycle and the two following cycles during which patients were taking their assigned study medication. All patients received a 5-HT₃ receptor antagonist antiemetic on day one of all cycles. Patients took three capsules of ginger (250 mg) or placebo twice daily for six days starting three days before the first day of chemotherapy. Patients reported the severity of nausea for days 1–4 of each cycle, four times daily.  Compliance was determined by pill counts.

• The sample consisted of 576 patients.
• Mean age was 53 years.
• The sample was 91% female.
• All participants had been diagnosed with cancer and were receiving chemotherapy.
• All patients had to have experienced nausea in a previous chemotherapy cycle and be scheduled to receive a 5-HT₃ plus dexamethasone for antiemetic management. 
• Baseline values showed that more than 50% of the sample had had previous chemotherapy. Baseline nausea ranged from 2.2–2.5.

This was a multisite study conducted at 23 private practice oncology groups  affiliated with the University of Rochester.

• Patients were in mutliple phases of care.
• Applications exist for palliative care.

This was a phase II/III randomized, double blind, placebo-controlled clinical trial.

• Nausea and emesis were measured on a 7-point scale using a modified four-day patient report diary developed by Burish and Carey.
• A 13-item Symptom Inventory was used to assess potential side effects of ginger, as well as anticipatory nausea, on an 11-point scale.
• Anticipatory nausea was analyzed using the nausea item on the Symptom Inventory completed prior to chemotherapy.
• Quality of life was assessed using the 27-item Functional Assessment of Chronic Illness Therapy-General (FACIT-G) at baseline and follow-up assessments .

• No significant differences were found between the treatment arms in regard to the use of antiemetics.
• The mixed model analyses across both study cycles 2 and 3 revealed that all doses of ginger significantly reduced acute CIN in both study cycles compared to placebo (p = 0.013, 0.003). Differences in the least-squares means showed that 0.5 g and 1.0 g daily ginger were the most effective at reducing acute nausea.
• Data suggested that patients reported more severe delayed nausea compared to acute nausea, and no differences were found between groups in delayed nausea.
• Overall, no significant differences were observed in vomiting or quality of life between the three ginger arms and placebo.
• The majority of patients did not report episodes of vomiting (mean incidence = 0.5). 
• Analysis revealed that anticipatory nausea (p < 0.0001) was a factor in acute CIN.
• A total of 24 adverse events were reported during the course of the study. Only nine of the reported adverse advents were considered to be related to study drug.

Ginger given at 0.5 g-1.0 g daily, may aid in the reduction of acute-phase CIN in patients receiving standard antiemetics. The ability to clearly interpret results is difficult because of lack of information on chemotherapy agents involved and differences in antiemetic regimens used.

• The chemotherapy agents used were not described, so the emetogenicity of the treatment or potential differences between groups, which could have affected results, are not known. 
• No discussion was provided regarding use or non-use of rescue medications or any other management strategies that may have been used.
• The antiemetic regimens used were varied, and it is known that different regimens have different levels of effect. 
• Though inclusion criteria identified use of 5-HT₃ medication, results reported show that four different types of regimens were actually employed.

This study showed that ginger significantly reduced nausea in these patients during the acute phase but had no apparent effect on delayed nausea. Studies in the use of ginger have had mixed results, and meta analysis have shown no effect, in contrast to this study. Here, only nausea was examined, which may partially explain differences. Application of these findings is difficult, because the chemotherapy regimens used are not described, so emetogenicity or differences in regimens between groups cannot be evaluated. Also, the antiemetic medications used were varied and subgroup analysis was not done; how this influenced findings is not clear. Even with maximum current pharmacologic management of chemotherapy-induced nausea and vomiting, control of nausea, as opposed to vomiting, has remained problematic. Further research in approaches to effectively manage nausea, as well as emesis is needed.