Gabapentin

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

• 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

• 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

• 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

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

• PHASE OF CARE: Active antitumor treatment
• APPLICATIONS: Palliative care

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

• 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)

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.

• 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.

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

To evaluate the efficacy and safety of gabapentin for the prevention of acute and delayed chemotherapy-induced nausea and vomiting (CINV) during the first cycle of moderately or highly emetogenic chemotherapy

Chemotherapy naïve patients with cancer who were scheduled to begin moderately or highly emetogenic chemotherapy were randomized to either receive 300 mg gabapentin or a placebo, in addition to a standard regimen of antiemetic prophylaxis (8 mg IV ondansetron, 10 mg IV dexamethasone, and 50 mg IV ranitidine before chemotherapy on day 1 and 4 mg oral dexamethasone twice a day on days 2 and 3).

Patients received either the gabapentin or the placebo five and four days before chemotherapy, once per day; three and two days before chemotherapy, twice per day; and one day before through five days after chemotherapy, three times per day. After chemotherapy was administered until the morning of day 5, patients kept diaries to record episodes of emesis or retching and severity of nausea over the previous 24 hours.

The primary outcome of this study was an evaluation of the number of patients reporting a complete response (CR), defined as the absence of nausea and vomiting and no use of rescue medications, during three timeframes.

• Acute phase of treatment (starting after chemotherapy was administered and ending 24 hours later)
• Delayed phase (starting 24 hours after chemotherapy was administered and ending on day 5 of treatment)
• Overall

• The study consisted of 80 patients.
• The mean age of patients was 53.95 years (SD = 10.15 years).
• The majority of the sample was female (93.75%).
• Cancer diagnoses were lung, breast, and head and neck cancer.
• Patients were chemotherapy-naive and scheduled to receive moderately or highly emetogenic chemotherapy (cisplatin greater than 60 mg/m² or doxorubicin greater than 50 mg/m²).

The study was conducted at a single site at a large medical institution in Brazil.

All patients were in active treatment.

This was a randomized, double-blind, placebo-controlled trial.

• Patients recorded episodes of vomiting or retching using diaries. Patients were asked to record each episode of emesis or retching from the morning of chemotherapy administration until the morning of the sixth day after.
• Nausea was recorded using diaries. Patients were asked to record the intensity of their nausea over the last 24 hours on a 100-mm visual analog scale (VAS) ranging from ”no nausea” to ”nausea as bad as it could be” from the morning of chemotherapy administration until the morning of the sixth day after.
• Patients recorded the impact of CINV on daily life via the Functional of Living Index-Emesis (FLIE).
• Use of rescue medication was recorded in diaries. Patients were asked to record each instance a medication was taken to control nausea or emesis from the morning of chemotherapy administration until the morning of the sixth day after.
• Adverse events were recorded at the post-study visit on day 6 using the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0.

• Patients who received gabapentin in addition to the standard regimen of antiemetic prophylaxis were significantly more likely to experience CR compared to those who received a placebo and standard antiemetic prophylaxis (p = 0.04).
• Patients taking gabapentin also were significantly more likely to experience CR during the acute phase of treatment (the first 24 hours after chemotherapy administration) compared to the placebo group.
• No difference was found between groups for episodes of CR during the delayed phase of treatment (24 hours after chemotherapy administration up to day 5).
• No adverse events were reported.

Gabapentin may be a low-cost, nausea prophylaxis medication that can be used as an alternative to more expensive antiemetic medications. Although the authors described gabapentin as a low-risk medication, recent reports have linked gabapentin to increased rates of depression and suicide. It also has been commonly associated with the side-effects of drowsiness and dizziness.

• This study involved a small sample of fewer than 100 participants.
• The study sample was predominantly women with breast cancer. Generalizing to other cancers and men is difficult.
• The comparative standard regimen did not include an NK1, which is recommended as of this writing.

For patients who are uninsured or underinsured and those living in developing countries where obtaining high-cost medications may be difficult, gabapentin may prove useful as a less-expensive alternative antiemetic prophylactic medication. Research should attempt to compare less expensive alternatives with current best practices.