An international open-label randomised trial comparing a two-step approach versus the standard three-step approach of the WHO analgesic ladder in patients with cancer.

BACKGROUND: Worldwide, cancer pain management follows the WHO three step analgesic ladder. Using weak opioids (e.g. codeine) at step two is debatable with low dose strong opioids potentially better, particularly in low and middle-income countries where weak opioids are expensive. We wanted to assess the efficiency, safety and cost of omitting step two of the WHO ladder.

PATIENTS AND METHODS: We did an international, open label, randomised (1:1) parallel group trial. Eligible patients had cancer, pain >4/10 on a 0-10 Numerical Rating Scale (NRS), required at least step 1 (paracetamol) of the WHO ladder and were randomised to the control arm (weak opioid, step two of the WHO ladder) or the experimental arm (strong opioid, step three). Primary outcome was time to stable pain control, (three consecutive days with pain ≤3). Secondary outcomes included distress, opioid related side-effects and costs. The primary outcome analysis was by intention to treat and follow up was for 20 days.

RESULTS: 153 patients were randomised, (76 control, 77 experimental). There was no statistically significant difference in time to stable pain control between the arms, p=0.667 (log rank test). The adjusted hazard ratio for the control arm was, 1.03, 95% CI 0.72 to 1.49. In the control arm, 38 patients (53%) needed to change to a strong opioid due to ineffective analgesia. The median time to change was day 6 (IQR 4-11). Compared to the control arm, patients in the experimental arm had less nausea (p=0.009) and costs were less.

CONCLUSION: This trial provides some evidence that the two-step approach is an alternative option for cancer pain management.