title: The second step of the analgesic ladder and oral tramadol in the treatment of mild to moderate cancer pain: a systematic review.
abstract: BACKGROUND
  To analyse the evidence supporting the widespread use of modified analgesic ladders or oral tramadol as alternatives to codeine/paracetamol for mild to moderate cancer pain.
  
  
  METHODS
  A systematic review of the literature was independently performed by two authors. The level of evidence and risk/benefit ratio were assessed in all the selected trials. A comprehensive analysis of the level of evidence, risk/benefit ratio and strength of the recommendations was carried out. The analysis was performed using the GRADE system.
  
  
  RESULTS
  Eighteen papers were included into the analysis. The level of evidence was low or very low for all the trials, and as a result the risk/benefit ratio was uncertain. Likewise, the strength of the final recommendations was considered weak negative for either the use of modified analgesic ladders (by-passing the second step of the World Health Organization (WHO) analgesic ladder) or the use of oral tramadol as an alternative to codeine/paracetamol in the second step of the WHO analgesic ladder.
  
  
  CONCLUSIONS
  Data supporting the role of modified two-step analgesic ladders or oral tramadol as an alternative to codeine/paracetamol are insufficient to recommend their routine use in cancer patients with mild to moderate cancer pain.
authors.affiliation: Department of Oncology, City Hospital, Italy. dtassinari@rimini.com
authors.forename: Davide
authors.initials: D
authors.lastname: Tassinari
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Drudi
authors.forename: Marta
authors.initials: M
authors.lastname: Rosati
authors.forename: Paola
authors.initials: P
authors.lastname: Tombesi
authors.forename: Sergio
authors.initials: S
authors.lastname: Sartori
authors.forename: Marco
authors.initials: M
authors.lastname: Maltoni
mesh_terms: D000701:Analgesics, Opioid / Q000627:therapeutic use*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D003061:Codeine / Q000627:therapeutic use; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy*; D010146:Pain / Q000188:drug therapy*; D010147:Pain Measurement; D017410:Practice Guidelines as Topic; D012720:Severity of Illness Index; D014147:Tramadol / Q000627:therapeutic use*
chemical_list: D000701:Analgesics, Opioid; D000894:Anti-Inflammatory Agents, Non-Steroidal; D014147:Tramadol; D003061:Codeine