• Daniele Santini, Gaetano Lanzetta, Emanuela Dell'Aquila, Bruno Vincenzi, Olga Venditti, Marco Russano, Nicola Papapietro, Vincenzo Denaro, Giuseppe Tonini, and Carla Ripamonti.
• University Campus Bio-Medico Roma, Oncologia Medica, Rome, Italy. d.santini@unicampus.it
• Expert Opin Pharmacother. 2013 Mar 1;14(4):425-33.

IntroductionMore than 20 years ago the World Health Organization (WHO) published the booklet 'Cancer Pain Relief', including the fundamentals and clear principles, which was summarized in five simple sentences: 'by mouth', 'by the clock', 'by the ladder', 'for the individual' and 'attention to detail'. Over the years, several modifications to the analgesic ladder have been proposed, as the addition of two further steps, related to the switch of opioid and/or non-invasive route of administration, and to the use of invasive approaches, or again the skip of the second step; nevertheless the educational value and benefits related to the worldwide dissemination are of paramount importance.Areas CoveredTo date, all the guidelines are inspired by the strategy of WHO; below some of the most important international guidelines published in the last two years are compared, particularly as regards the criteria of choice of opioids for moderate/severe pain.Expert OpinionThe discussion on the role of the second step of the WHO analgesic ladder is still open. The challenge for new formulations of 'old' opioids will be to better manage cancer pain, with more tailored efficacy and possibly less side effects.

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