Phase III double‐blind, placebo‐controlled study of gabapentin for the prevention of delayed chemotherapy‐induced nausea and vomiting in patients receiving highly emetogenic chemotherapy, NCCTG N08C3 (Alliance)

Abstract

BACKGROUND: Despite targeted antiemetics, data support an unmet need related to the management of delayed nausea and vomiting (NV). Promising pilot data informed this phase III trial evaluating gabapentin for delayed NV from highly emetogenic chemotherapy (HEC). METHODS: Participants were randomized to receive prophylactic treatment with 20 mg of dexamethasone and a 5HT3 receptor antagonist (RA) on the day of chemotherapy, followed by gabapentin 300 mg twice a day and dexamethasone (dex) or placebo and dex after HEC. Gabapentin/placebo was started the day of chemotherapy and continued through day 5 for the first chemotherapy cycle, whereas dex was titrated down on days 2-4. The primary end point was complete response (CR), defined as no emesis and no use of rescue medications on days 2-6, using an NV diary. The percentages of those in each group with a CR were compared by Fisher's exact test. RESULTS: Four hundred thirty patients were enrolled in this study. Forty-seven percent of patients in the gabapentin arm and 41% in the placebo arm had a CR (P 5.23). Mean number of emesis episodes was <0.5 daily, and mean nausea severity was < 2 (mild). In both arms, patient satisfaction with NV control was greater than 8 (with 10 being perfectly satisfied). There were no significant differences in unwanted side effects. CONCLUSIONS: In this study, gabapentin did not significantly improve delayed NV. Patients were satisfied with the control of their nausea and vomiting irrespective of arm. The use of a 5HT3 RA and dexamethasone provided good control of nausea and vomiting for most patients. Cancer 2014;120:3575-83.

Chemotherapy-induced nausea and vomiting: incidence and characteristics of persistent symptoms and future directions NCCTG N08C3 (Alliance)

“…This trial was negative, showing no difference in complete response rates (defined as no emesis and no rescue medications on days 2 through 6) between the two therapy arms [6]. N08C3 demonstrated complete response rates for delayed nausea and vomiting of 47 and 41 % ( P = 0.23) in the gabapentin and placebo arms, respectively.…”

“…N08C3 demonstrated complete response rates for delayed nausea and vomiting of 47 and 41 % ( P = 0.23) in the gabapentin and placebo arms, respectively. Despite the lower than expected complete response rates (less than 50 %), participants rated their overall satisfaction for the control of nausea and vomiting (days 2–6) at a mean of 8.7 (range 0–10 with 10 being completely satisfied) in the group receiving gabapentin and 8.5 in the placebo group [6]. Due to the high rate of satisfaction but lower than expected complete response rates, we re-examined the N08C3 data with the following objectives in mind.…”

An investigation into the effect of gabapentin capsules on the reduction of nausea and vomiting after chemotherapy in cancerous patients under platinum-based treatment

“…This dosage remained constant for up to 72 hours after chemotherapy, while it did not agree well with the placebo group for up to 72 hours, given a decrase in the CINV in the gabapentin group. [1417181920]…”

Moxibustion for Chemotherapy‐Induced Nausea and Vomiting: A Systematic Review and Meta‐Analysis

“…According to the ASCO guideline, five 5-HT3 receptor antagonists (dolasetron, granisetron, ondansetron, palonosetron, and tropisetron) have equivalent efficacy at the same doses. One meta-analysis [ 34 ] revealed no difference among ondansetron, granisetron, and dolasetron mesylate. Among the trials comparing moxibustion with antiemetic drugs, four trials [ 17 , 18 , 21 , 23 ] measured the outcomes by using the WHO criterion.…”