Barton, D.L., Thanarajasingam, G., Sloan, J.A., Diekmann, B., Fuloria, J., Kottschade, L.A., . . . Loprinzi, C.L. (2014). 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, 120, 3575–3583.

DOI Link

Study Purpose

To compare gabapentin to a placebo on three factors: efficacy in decreasing CINV, tolerability to the medication, and impact on quality of life.

Intervention Characteristics/Basic Study Process

All patients received the same prophylactic regimen.

Day 1: 20 mg of dexamethasone and a 5HT3 receptor antagonist
Days 2 and 3: 8 mg of dexamethasone two times per day with or without a 5HT3 receptor antagonist
Day 4: 4 mg of dexamethasone two times per day with or without a 5HT3 receptor antagonist

The patients also received either gabapentin or a placebo on the following schedule:

Day 1: One tablet (300 mg gabapentin/placebo) in the evening
Days 2 and 3: One tablet (300 mg gabapentin/placebo) two times per day
Days 4 and 5: One tablet (300 mg gabapentin/placebo) two times per day or three times per day

Data were collected on the six days following administration of chemotherapy.

Sample Characteristics

N = 413
AGE ≥ 50 years (73% in the gabapentin arm, 72% in the placebo arm)
MALES: 30%, FEMALES: 70%
KEY DISEASE CHARACTERISTICS: Breast, lung, colorectal, gynecologic, and hematologic cancers among others
OTHER KEY SAMPLE CHARACTERISTICS: Performance status of 0–2, chemotherapy naive for highly emetogenic and moderately emetogenic chemotherapy; able to swallow pills; first cycle of chemotherapy

Setting

SITE: Multi-site
SETTING TYPE: Outpatient
LOCATION: United States

Phase of Care and Clinical Applications

PHASE OF CARE: Active antitumor treatment
APPLICATIONS: Palliative care

Study Design

This phase 3 study was a placebo-controlled trial that was randomized and double-blinded.

Measurement Instruments/Methods

The patients kept a nausea and vomiting diary
Numeric analog scales were used daily to measure average level of nausea, worst level of nausea, treatment satisfaction, and distress.
The use of any rescue medications were recorded.
Satisfaction with treatment and distress were recorded using a numeric analog scale.
National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) to grade edema, somnolence, dizziness, and ataxia
Patients used a self-report analog scale to measure loss of appetite, mood swings, diarrhea, fatigue, impaired concentration, and drowsiness.
Functional Living Index-Emesis (FLIE)

Results

A complete response (CR) was defined as no required rescue antiemetics and no episodes of emesis on days 2–6. In the gabapentin arm, 47% (97) of patients achieved CR. In the placebo arm, 41% (84) experienced CR. In both arms, 30% (62) reported vomiting. Rescue medications were taken by 45% (93) of patients taking gabapentin and 53% (109) of those taking a placebo. The daily mean for either arm for vomiting was < 0.5 and the mean for the severity of nausea was < 1.5.

The CTCAE was used to measure toxicities, and there was not a statistically significant difference in toxicities between the two arms.

Conclusions

This study did not support the effectiveness of gabapentin as prophylaxis for delayed chemotherapy-induced nausea and vomiting when used in conjunction with dexamethasone and a 5HT3 receptor antagonist.

Limitations

Risk of bias (sample characteristics)
Findings not generalizable
Other limitations/explanation: The authors defined highly emetogenic chemotherapy as a cisplatin-based regimen; however, several other chemotherapies are also highly emetogenic. Because the authors did not include all high-risk chemotherapies, the sample characteristics may be biased and the findings may not be generalizable to other highly emetogenic chemotherapies.

Nursing Implications

Based on this study, gabapentin is not recommended as prophylaxis for delayed chemotherapy-induced nausea and vomiting.