Gabapentin in Preventing Nausea and Vomiting in Patients Receiving Chemotherapy

OBJECTIVES:

- To evaluate the effectiveness of gabapentin in controlling delayed chemotherapy-induced
nausea and vomiting (CINV) in patients receiving highly emetogenic chemotherapy as
defined by the percentage of complete responders (no emetic episodes and no rescue
medication) on days 2 through 6 (five days after receipt of highly emetogenic
chemotherapy) compared to an effective prophylactic regimen.

- To evaluate the effectiveness of gabapentin in controlling delayed CINV in patients
receiving highly emetogenic chemotherapy as defined by the percentage of complete
responders (no emetic episodes, no more than mild nausea, and no rescue medication) on
days 2 through 6 compared to an effective prophylactic regimen.

- To compare the effectiveness of these regimens in controlling acute CINV on day 1 of
treatment in these patients.

- To compare the use of rescue agents in these patients.

- To determine the tolerability of gabapentin in these patients.

- To evaluate the effect of gabapentin for delayed chemotherapy-induced nausea and
vomiting on symptom distress and functional abilities in these patients.

- To compare alternative endpoints and methods for assessing nausea and vomiting and to
determine how these measures compare to patient's satisfaction with symptom control,
distress and function.

OUTLINE: This is a multicenter study. Patients are stratified according to gender, age (< 50
years vs > 50 years), history of alcoholism (yes vs no), and history of motion sickness or
history of pregnancy induced nausea/vomiting (yes vs no). Patients are randomized to 1 of 2
treatment arms.

- Arm I: Patients receive oral dexamethasone with 5HT3 receptor antagonist and oral
gabapentin once daily on day 1 of chemotherapy. Patients then receive oral
dexamethasone twice daily with or without 5HT3 receptor antagonist on days 2-4, and
oral gabapentin either two or three times daily on days 2-5 of chemotherapy.

- Arm II: Patients receive oral dexamethasone with 5HT3 receptor antagonist and oral
placebo once daily on day 1 of chemotherapy. Patients then receive oral dexamethasone
twice daily with or without 5HT3 receptor antagonist on days 2-4, and oral placebo
either two or three times daily on days 2-5 of chemotherapy.

Patients complete a Functional Living Index - Emesis questionnaire, an overall satisfaction
survey, and a side effect experience diary at baseline and on day 6. Patients also complete
a nausea and vomiting diary at baseline and periodically during study therapy.

DISEASE CHARACTERISTICS:

- Scheduled to receive highly emetogenic chemotherapy

- May be scheduled to receive prophylactic treatment for acute nausea and vomiting
with a 5HT3 antagonist and dexamethasone 20 mg on day 1 of chemotherapy
treatment

- May be scheduled to receive multiple day chemotherapy regimens as long as the
chemotherapy drugs given on the subsequent days have mild or no emetogenic
potential

- Chemotherapy schedules must allow at least 7 days rest between courses involving
administration of highly emetogenic chemotherapy

- No primary CNS malignancy and/or CNS metastasis

PATIENT CHARACTERISTICS:

- Eastern Cooperative Oncology Group (ECOG) performance status 0-2

- Life expectancy ≥ 3 months

- Creatinine ≤ 1.5 times upper limit of normal within the past 30 days

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- Ability to complete questionnaire(s) by his/herself or with assistance

- Able to swallow pills

- No epilepsy or seizure history

- No gastrointestinal obstruction, active peptic ulcer disease, or uncontrolled
heartburn

- No history of nausea and/or vomiting related to any kind of chemotherapy

- No nausea or vomiting within the past 3 days

- No history of allergic or other adverse reaction to gabapentin or pregabalin

PRIOR CONCURRENT THERAPY:

- See Disease Characteristics

- No prior moderate or highly emetogenic chemotherapy

- No prior or concurrent aprepitant or any other NK-1 receptor antagonist

- At least 1 months since prior and no concurrent gabapentin, pregabalin, or other
anticonvulsants

- At least 7 days since prior and no concurrent pelvic or abdominal radiotherapy

- At least 3 days since prior antiemetics

- No concurrent or planned use of lorazepam, diphenhydramine, eszopiclone, and/or
dronabinol during the 6 days of this study, except for treatment of breakthrough
nausea and vomiting