Randomised phase II trial (NCT00637975) evaluating activity and toxicity of two different escalating strategies for pregabalin and oxycodone combination therapy for neuropathic pain in cancer patients

PLoS One. 2013;8(4):e59981. doi: 10.1371/journal.pone.0059981. Epub 2013 Apr 5.

Abstract

Purpose: Neuropathic pain is commonly associated with cancer. Current treatments include combination opioid and adjuvant therapies, but no guidelines are available for dose escalation strategies. This phase II study compared the efficacy and tolerability of two dose escalation strategies for oxycodone and pregabalin combination therapy.

Methods: Patients (N = 75) with oncological neuropathic pain, previously untreated with pregabalin, were recruited in 5 Italian institutions between 2007 and 2010. Patients were randomised to two different dose escalation strategies (arm A; N = 38) oxycodone at a fixed dose with increasing pregabalin doses; (arm B; N = 37) pregabalin at a fixed dose with increasing oxycodone doses. Patients were evaluated from daily diaries and follow-ups at 3, 7, 10, and 14 days after beginning treatment with a numerical rating scale (NRS), neuropathic pain scale (SDN), and well-being scale (ESAS). The primary endpoint was a ≥1/3 reduction in pain (NRS); secondary endpoints included the time to analgesia and adverse effects. The study had a 90% probability of detecting the best strategy for a true difference of at least 15%.

Results: More patients in arm A (76%) than arm B (64%) achieved ≥1/3 overall pain reduction even after controlling for baseline factors (gender, baseline pain). Group A reported fewer side effects than group B; constipation 52.8% vs. 66.7%; nausea: 27.8% vs. 44.4%; drowsiness: 44.4% vs. 55.6%; confusion: 16.7% vs. 27.8%; itching: 8.3% vs. 19.4%.

Conclusions: Both strategies effectively controlled neuropathic pain, but according to the adopted selection design arm A is preferable to arm B for pain control.

Trial registration: ClinicalTrials.gov NCT00637975.

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Dose-Response Relationship, Drug
  • Drug Therapy, Combination
  • Female
  • Humans
  • Male
  • Middle Aged
  • Neoplasms / complications*
  • Neuralgia / complications*
  • Neuralgia / drug therapy*
  • Neuralgia / genetics
  • Oxycodone / adverse effects*
  • Oxycodone / therapeutic use*
  • Polymorphism, Single Nucleotide
  • Pregabalin
  • Treatment Outcome
  • gamma-Aminobutyric Acid / adverse effects
  • gamma-Aminobutyric Acid / analogs & derivatives*
  • gamma-Aminobutyric Acid / therapeutic use

Substances

  • Pregabalin
  • gamma-Aminobutyric Acid
  • Oxycodone

Associated data

  • ClinicalTrials.gov/NCT00637975

Grants and funding

Funding was received from the UMAN.A project, a recognised non-profit social assistance organisation (Onlus). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.