title: 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.
abstract: OBJECTIVE
  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.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT00637975.
authors.affiliation: Medical Oncology Unit 1, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: Marina Chiara
authors.initials: MC
authors.lastname: Garassino
authors.forename: Sheila
authors.initials: S
authors.lastname: Piva
authors.forename: Nicla
authors.initials: N
authors.lastname: La Verde
authors.forename: Ilaria
authors.initials: I
authors.lastname: Spagnoletti
authors.forename: Vittorio
authors.initials: V
authors.lastname: Iorno
authors.forename: Claudia
authors.initials: C
authors.lastname: Carbone
authors.forename: Antonio
authors.initials: A
authors.lastname: Febbraro
authors.forename: Anna
authors.initials: A
authors.lastname: Bianchi
authors.forename: Annalisa
authors.initials: A
authors.lastname: Bramati
authors.forename: Anna
authors.initials: A
authors.lastname: Moretti
authors.forename: Monica
authors.initials: M
authors.lastname: Ganzinelli
authors.forename: Mirko
authors.initials: M
authors.lastname: Marabese
authors.forename: Marta
authors.initials: M
authors.lastname: Gentili
authors.forename: Valter
authors.initials: V
authors.lastname: Torri
authors.forename: Gabriella
authors.initials: G
authors.lastname: Farina
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000150:complications*; D009437:Neuralgia / Q000150:complications* / Q000188:drug therapy* / Q000235:genetics; D010098:Oxycodone / Q000009:adverse effects* / Q000627:therapeutic use*; D020641:Polymorphism, Single Nucleotide; D000069583:Pregabalin; D016896:Treatment Outcome; D005680:gamma-Aminobutyric Acid / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D000069583:Pregabalin; D005680:gamma-Aminobutyric Acid; D010098:Oxycodone