The second step of the analgesic ladder and oral tramadol in the treatment of mild to moderate cancer pain: A systematic review

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.