Rao, R.D., Michalak, J.C., Sloan, J.A., Loprinzi, C.L., Soori, G.S., Nikcevich, D.A., . . . Wong, G.Y. (2007). Efficacy of gabapentin in the management of chemotherapy-induced peripheral neuropathy. Cancer, 110, 2110–2118. doi: 10.1002/cncr.23008

115 patients with symptomatic chemotherapy-induced peripheral neuropathy (CIPN) were randomized to the order of receiving oral gabapentin or placebo for six weeks separated by a two week “washout” period and crossing over to the other treatment group for six weeks. Gabapentin doses (300 mg capsules) and identical placebo doses were escalated over three weeks to a target dose of 2,700 mg of gabapentin per day, or nine placebo capsules per day.

• N = 115
• n = 57 assigned to receive gabapentin first
• n = 58 assigned to  receive placebo first.
• 115 adult patients with longer than one month duration of symptomatic CIPN who reported scores of 4 or higher for average pain on a 0–10 numeric rating scale (NRS), or a score of 1 or higher on the Eastern Cooperative Oncology Group (ECOG) neurosensory (ENS) toxicity item (possible ENS scores are 0–3, with 1 defined as mild paresthesias [loss of deep tendon reflexes]).
• Fifty percent of the participants were receiving chemotherapy at study entry. 
• Exclusion criteria included preexisting neuropathy and use of antidepressants, opioids, adjuvant analgesics, topical analgesics, and/or amifostine at baseline.
• Stratified random assignment was used with stratification on type of chemotherapy and whether patients were receiving chemotherapy or had completed chemotherapy.

The study was a phase III randomized, double-blind, placebo-controlled crossover trial.

Primary outcomes were pain and neuropathy symptoms measured by NRS (0 = no pain and 10 = worst pain possible) and the ENS (0 = none and 3 = severe objective sensory loss or paresthesias that interfere with function). These self-report data were collected weekly in reference to a single day

Secondary measures included:

• Tthe World Health Organization (WHO) classification scale for neuropathy-related symptoms
• The Short Form-McGill Pain Questionnaire
• The Brief Pain Inventory-Short Form
• The Subjective Global Impression of Change
• The Symptom Distress Scale
• The Profile of Mood States (POMS) Short Form
• And a quality of life uniscale.

These data were collected at baseline, 6, 8, and 14 weeks.

No differences were noted between groups at baseline, 6, or 14 weeks in the average pain NRS and the ENS. However, worst pain was lower in the placebo followed by gabapentin group at 14 weeks (p = 0.05). The only significant difference between the groups was in the McGill Pain Rating Index, which showed lower pain in the gabapentin group at the end of the first six week treatment period (p = 0.03).

Gabapentin did not improve symptoms of CIPN.

• A mixed sample of varying cancers, treatments, and time since chemotherapy could confound results.
• Patients with greater severity of pain may benefit from gabapentin. However, these patients were excluded from the study as they were taking opioids prior to the start of the study.
• Forty percent of the participants between the two groups were lost to follow-up (115 started treatment and 68 completed treatment).
• Because the eight-week results were not presented, it is not possible to determine if the groups were equivalent at the beginning of the second treatment period. Data on the POMS total and subscale scores were not included. 
• The means presented  at baseline did not include scores from participants who dropped out of the study.
• The authors noted that using separate tests at each time point without adjusting the alpha level to compensate may have contributed to the inconsistent findings among the pain instruments. 
• The ENS instrument considers that all parasthesias involve pain through subjective report and this may then increase or decrease depending on the amount of error in self report and can prove to be problematic when interpreting the results.