Study Supports More Aggressive Approach to Managing Cancer Pain

Patients with moderate cancer pain report significantly greater pain relief after taking low-lose morphine as opposed to weaker opioids, according to a recent study. The results suggest that starting with strong opioids might be a better pain management strategy than following the standard three-step analgesic ladder recommended by current guidelines.

In a multicenter, open-label, randomized controlled trial, 240 adults with moderate cancer pain received either a weak opioid, such as codeine with paracetamol or tramadol, or low-dose morphine for 28 days, and rated their pain intensity on a numerical scale. Just over 88% of patients in the morphine group achieved a 20% reduction in pain intensity-the primary outcome of the study-vs 58% in the weak opioid group. The findings were published in the Journal of Clinical Oncology.

“In this study, low-dose morphine was much better in controlling pain than a weak opioid, which could have important implications for the way we treat moderate pain in our patients,” said Don Dizon, MD, an expert with the American Society of Clinical Oncology, who was not involved with the study. “However, due to the short duration of this study, more research is needed on the long-term effectiveness and safety of low-dose morphine in this setting.”

Current standard of care for cancer pain management follows guidelines set by the World Health Organization (WHO), which recommends a three-step process according to pain intensity: non-opioids, such as nonsteroidal anti-inflammatory drugs for mild pain; weak opioids for mild to moderate pain; and strong opioids for moderate to severe pain. However, other studies have shown that weak opioids often do not provide adequate pain relief for patients with moderate pain.

In practice, oncologists often move directly to strong opioids to treat moderate pain but the strategy lacks strong evidence since previous studies were smaller and reported inconclusive results, noted Mario Luppi, MD, PhD, of the University of Modena and Reggio Emilia in Modena, Italy, and coauthors. In contrast, the current study involves a large, representative cohort of patients and offers convincing evidence that low-dose morphine can substitute for weak opioids in the setting of moderate cancer pain.

The study supports simplifying the WHO pain ladder by skipping the second step, thereby increasing patient access to strong opioids earlier in the disease process and improving overall pain control, according to an accompanying editorial by Stein Kaasa, MD, PhD, a palliative care expert in the department of oncology at Oslo University Hospital in Norway. However, experts should await results from another ongoing trial based at the University of Edinburgh, which is comparing a two-step with a three-step opioid approach in an estimated 450 patients.

In addition to refining how physicians manage pain, improvements are needed in how pain is diagnosed, said Kaasa. The upcoming 11th revision of the International Classification of Diseases contains a new classification of chronic cancer pain that takes into account both pain caused by the disease itself and pain caused by cancer treatment. Kaasa noted that patient-reported outcome measures should also be used to classify pain and help guide treatment.

Ultimately, opioid treatment must be part of a more comprehensive strategy to pain management that includes other pain control methods and individualized support.

“Without a multidisciplinary effort to provide continuity of care for complex patients, pain relief will be insufficient,” Kaasa concluded. “Pain control must be part of a strategy that includes control of other symptoms, psychosocial support, and integration between oncology and palliative care services to meet the complex needs of patients and their families.”