Ginger (Zingiber officinale) reduces acute chemotherapy-induced nausea: a URCC CCOP study of 576 patients

Abstract

Purpose: Despite the widespread use of antiemetics, nausea continues to be reported by over 70% of patients receiving chemotherapy.

Methods: In this double blind, multicenter trial, we randomly assigned 744 cancer patients to four arms: 1) placebo, 2) 0.5 g ginger, 3) 1.0 g ginger, or 4) 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-HT(3) receptor antagonist antiemetic on Day 1 of all cycles. Patients took three capsules of ginger (250 mg) or placebo twice daily for 6 days starting 3 days before the first day of chemotherapy. Patients reported the severity of nausea on a 7-point rating scale ("1" = "Not at all Nauseated" and "7" = "Extremely Nauseated") for Days 1-4 of each cycle. The primary outcomes were to determine the dose and efficacy of ginger at reducing the severity of chemotherapy-induced nausea on Day 1 of chemotherapy.

Results: A total of 576 patients were included in final analysis (91% female, mean age = 53). Mixed model analyses demonstrated that all doses of ginger significantly reduced acute nausea severity compared to placebo on Day 1 of chemotherapy (p = 0.003). The largest reduction in nausea intensity occurred with 0.5 g and 1.0 g of ginger (p = 0.017 and p = 0.036, respectively). Anticipatory nausea was a key factor in acute chemotherapy-induced nausea (p < 0.0001).

Conclusions: Ginger supplementation at a daily dose of 0.5 g-1.0 g significantly aids in reduction of the severity of acute chemotherapy-induced nausea in adult cancer patients.

Conflict of interest statement

None of the authors have conflicts of interest to disclose.

Figures

Figure 1. Patient Flow Diagram

A total of 744 patients were consented and randomized into one of four treatment arms (placebo, 0.5g Ginger, 1.0g Ginger, or 1.5g Ginger). There was no significant difference in the dropout rate between treatment arms or study cycle. Only 469 patients fully completed the study, although data was evaluable for 576 patients and included in the analyses.

Figure 2. Ginger reduces severity of acute chemotherapy-induced nausea

The boxplots represent the mean change in average nausea severity (NAv in left panel) and maximum nausea severity (NMx in right panel) for each treatment arm (i.e., ginger dose) on Day 1 of chemotherapy (i.e., acute CIN). Each shaded bar is a different treatment arm. All doses of ginger significantly reduced nausea severity on Day 1 of chemotherapy compared to placebo. The largest reduction in acute nausea occurred with 0.5g and 1.0g of ginger daily. Although Study Cycle 3 appears to show a greater reduction in nausea, there was no significant difference in mean nausea change between the two study cycles.

Figure 3. Average nausea severity (NAv) over time for each study cycle

Treatment arms are: placebo (•); 0.5g ginger (▴); 1.0g ginger (▪); 1.5g ginger (┼). Acute phase represents evening and night of Day 1 diary nausea responses, delayed phase represents all diary nausea responses on Day 2 and Day 3, and follow-up phase represents all diary nausea responses on Day 4. The top two graphs show the mean change in NAv severity for acute, delayed, and follow-up phases during study cycle 2 (left) and study cycle 3 (right). The middle two graphs show the NAv severity for acute, delayed, and follow-up phases during study cycle 2 and 3. The bottom two graphs show the NAv severity for acute, delayed, and follow-up phases during the baseline cycle for patients that continued to study cycle 2 and study cycle 3.

Figure 4. Maximum nausea severity (NMX) over time for each study cycle

Treatment arms are: placebo (•); 0.5g ginger (▴); 1.0g ginger (▪); 1.5g ginger (┼). Acute phase represents evening and night of Day 1 diary nausea responses, delayed phase represents all diary nausea responses on Day 2 and Day 3, and follow-up phase represents all diary nausea responses on Day 4. The top two graphs show the mean change in NMx severity for acute, delayed, and follow-up phases during study cycle 2 (left) and study cycle 3 (right). The middle two graphs show the NMx severity for acute, delayed, and follow-up phases during study cycle 2 and 3. The bottom two graphs show the NMx severity for acute, delayed, and follow-up phases during the baseline cycle for patients that continued to study cycle 2 and study cycle 3.