High doses of gabapentin are associated with pancreatic acinar cell tumors in rats, but there
has been no post marketing pancreatic carcinogenicity signal with gabapentin as reported by
spontaneous reports in AERS or in the published literature. In a published case-control
screening study of the association of gabapentin with 55 cancers, the only cancer that met
the screening criteria for possibly increased cancer risk with gabapentin exposure was renal
(including renal pelvis) cancer. This association was judged to be likely due to or
substantially accentuated by confounding by cigarette smoking, hypertension, and lifestyle
(Cancer Causes Control 2009;20:1821-1835).
The relationship between gabapentin exposure and pancreatic cancer and renal cancer is
studied in NCT01138124, and supplemental analyses for these cancers are performed in the
current study. The FDA recommended GSK also study the relationship between gabapentin and
all-cancer sites, as well as cancer at the following specific sites: 1) stomach, 2) anus,
anal canal, and anorectum, 3) lung and bronchus, 4) bones and joints, 5) breast, 6) penis, 7)
urinary bladder, and 8) other nervous system.
The primary objective of this study is to determine whether exposure to gabapentin is
associated with an increased risk of developing all-cancer, and these specific cancers in the
United Kingdom (UK) General Practice Research Database (GPRD). Each member of the UK
population is registered with a General Practice, which centralizes the medical information
not only from the general practitioners themselves but also from specialist referrals and
hospital attendances. Over 487 General Practices contribute data to the GPRD.
The study cohort from which cases and controls are drawn is all subjects in the GPRD
1993-2008. Gabapentin was approved in the UK in May 1993. Entry into the study cohort begins
Jan 1, 1993 for all those who are registered in GPRD before that time, and at the time of
registration if later than Jan 1, 1993. Subjects are excluded from the GPRD cohort if they
have a cancer diagnosis or a history of cancer prior to the cohort entry date. Patients with
a first diagnosis of the respective cancer 1995-2008 are risk set matched with up to 10
controls within the same General Practice for age at cohort entry (within two years), sex,
and year of entry into the study cohort (within one year). For cases, the index date is the
date of first diagnosis of the respective cancer. The index date for controls is set as the
date at which the follow-up time from cohort entry is the same as the case. The index date is
chosen so as to give the control equal follow-up time to that of the case for ascertainment
of use of gabapentin. Cases and controls will be required to have at least 2 years of
follow-up in the study cohort before their index date. Cases must have no history of any
other cancer diagnosis prior to the index date. Controls are required to be free of cancer
diagnosis in the database up to the control's index date.
Data on gabapentin prescriptions are obtained for cases and controls from study cohort entry
to the index date. Gabapentin exposure will be assessed as ever/never, number of
prescriptions, cumulative dose, and cumulative duration, with a 2 year lag period
incorporated to control for protopathic bias (gabapentin prescription for initial pain
symptoms of undiagnosed cancer) and latency (time between cancer onset and specific GPRD
cancer diagnosis).
Crude and adjusted odds ratios and 95% confidence intervals (CI) will be produced from
conditional logistic regression models, with additional analyses evaluating for
dose-response. Covariates include indications for gabapentin use and risk factors for each
cancer.