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)

Cancer. 2014 Nov 15;120(22):3575-83. doi: 10.1002/cncr.28892. Epub 2014 Jul 9.

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 = .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.

Keywords: antiemetic therapy; delayed nausea; delayed vomiting; gabapentin; randomized controlled trial.

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Amines / administration & dosage
  • Amines / adverse effects
  • Amines / therapeutic use*
  • Antineoplastic Agents / adverse effects*
  • Antineoplastic Agents / therapeutic use*
  • Cyclohexanecarboxylic Acids / administration & dosage
  • Cyclohexanecarboxylic Acids / adverse effects
  • Cyclohexanecarboxylic Acids / therapeutic use*
  • Double-Blind Method
  • Drug Administration Schedule
  • Female
  • Gabapentin
  • Humans
  • Male
  • Middle Aged
  • Nausea / chemically induced
  • Nausea / prevention & control*
  • Neoplasms / drug therapy*
  • Patient Satisfaction
  • Time Factors
  • Vomiting / chemically induced
  • Vomiting / prevention & control*
  • gamma-Aminobutyric Acid / administration & dosage
  • gamma-Aminobutyric Acid / adverse effects
  • gamma-Aminobutyric Acid / therapeutic use*

Substances

  • Amines
  • Antineoplastic Agents
  • Cyclohexanecarboxylic Acids
  • gamma-Aminobutyric Acid
  • Gabapentin