title: Long-term continuous subcutaneous infusion of ketoprofen combined with morphine: a safe and effective approach to cancer pain.
abstract: OBJECTIVE
  According to international guidelines, nonsteroidal anti-inflammatory drugs (NSAIDs) and opioids are the cornerstone drugs for cancer pain. In clinical practice, severe cancer pain often requires 3 step analgesics and alternative routes of administration, thus NSAIDs are usually abandoned. Our aim was to evaluate feasibility, safety, and efficacy of ketoprofen combined with opioids in long-term continuous subcutaneous infusion (CSI) for cancer pain in a prospective observational open-label pilot study.
  
  
  METHODS
  Ketoprofen was added to morphine CSI in 172 consecutive patients (study group, SG). Concomitantly, 48 received opioids CSI without ketoprofen for contraindication to NSAIDs (control group, CG). CSI was delivered through a single-use elastomeric pump refilled weekly. Safety was evaluated according to the number of adverse events and their severity. The measures of efficacy were pain relief (NRS, Numerical Rating Scale), percentage of patients that needed to increase morphine dosage, and median relative increase between weeks 2 and 4.
  
  
  RESULTS
  Toxicity typically attributable to NSAIDs were recorded in 4.1% of patients after 3 months of treatment and the combination of NSAIDs and corticosteroids seems not to influence the risk of gastrointestinal adverse effects. The local side effects related to the CSI regimen were negligible in both the groups. By the fourth week, pain was well controlled (NRS 0 to 2) in 80% of patients receiving ketoprofen compared with 46% of patients without ketoprofen (P<0.01.) Moreover, the percentage of patients needing to increase the morphine dosage (40.5% vs. 68.7% P<0.01) and the relative dose increase (12% vs. 25% P<0.005) were significantly lower in the SG.
  
  
  CONCLUSIONS
  Ketoprofen CSI in combination with opioids is a feasible, safe, and effective approach to cancer pain.
authors.affiliation: Department of Anaesthesiology, Intensive Care and Pain Therapy, IRCC - Institute for Cancer Research and Treatment, Candiolo, Torino. nmoselli@mauriziano.it
authors.forename: Nora Maria
authors.initials: NM
authors.lastname: Moselli
authors.forename: Mariaenrica
authors.initials: M
authors.lastname: Cruto
authors.forename: Paolo
authors.initials: P
authors.lastname: Massucco
authors.forename: Maurizio
authors.initials: M
authors.lastname: Savojardo
authors.forename: Felicino
authors.initials: F
authors.lastname: Debernardi
mesh_terms: D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination / Q000379:methods; D005260:Female; D006801:Humans; D055104:Infusions, Subcutaneous / Q000379:methods; D007660:Ketoprofen / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D009020:Morphine / Q000627:therapeutic use*; D009294:Narcotics / Q000627:therapeutic use*; D009369:Neoplasms / Q000150:complications; D010146:Pain / Q000188:drug therapy*; D010147:Pain Measurement / Q000379:methods; D012189:Retrospective Studies; D013997:Time Factors
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D009294:Narcotics; D009020:Morphine; D007660:Ketoprofen