Bandieri, E., Romero, M., Ripamonti, C.I., Artioli, F., Sichetti, D., Fanizza, C., . . . Luppi, M. (2016). Randomized trial of low-dose morphine versus weak opioids in moderate cancer pain. Journal of Clinical Oncology, 34, 436–442. 

DOI Link

Study Purpose

To evaluate the efficacy and tolerability of low dose morphine in comparison to standard doses of weak opioids in the treatment of moderate cancer pain in opioid naïve patients

Intervention Characteristics/Basic Study Process

This multicenter, 28-day, open-label randomized controlled study for adults with moderate cancer pain assigned to receive either a weak opioid or low dose of morphine was designed to evaluate the efficacy and tolerability of low dose morphine in comparison to standard doses of weak opioids in the treatment of moderate cancer pain in opioid naïve patients. The weak opioid group received either tramadol or codeine with or without paracetamol. The morphine group received morphine after a three-day titration phase with normal release morphine up to 30 mg per day. The groups were assessed every seven days.

Sample Characteristics

  • N = 240   
  • AGE = 59–74 years (WO group), 56–74 years (M group)
  • MEDIAN AGE = 68 years
  • MALES: 57% (WO group), 47.5% (M group); FEMALES: 43% (WO group), 52.5% (M group)
  • CURRENT TREATMENT: Chemotherapy
  • KEY DISEASE CHARACTERISTICS: Both solid tumors and hematologic tumors
  • OTHER KEY SAMPLE CHARACTERISTICS: Pain intensity, cancer symptoms, Karnofsky score, age, mental capacity

Setting

  • SITE: Multi-site   
  • SETTING TYPE: Multiple settings    
  • LOCATION: 17 Italian oncology centers

Phase of Care and Clinical Applications

  • PHASE OF CARE: Multiple phases of care
  • APPLICATIONS: Elder care, palliative care 

Study Design

  • Multicenter, 28-day, open-label, randomized controlled study

Measurement Instruments/Methods

  • Numerical Response Scale (0–10) for pain
  • Karnofsky Performance Status Scale, 60% or higher for patient functioning 
  • Edmonton Symptom Assessment System (ESAS) used to assess nine symptoms commonly experienced by patients with cancer during the previous 24 hours (validated in the Italian language)

Results

Primary endpoint of pain reduction of 20% or more from baseline was achieved in 88.2% of patients in the morphine group and 54.7% of patients in the weak opioid group (odds ratio = 6.18, 95% Cl [3.12, 12.24]; p < 0.001). Full adjustment for baseline covariates did not modify the results. The advantage of M over WO was evident at the first control at one week of observation (80.9% and 43.6%; p < 0.001) and remained constant at each follow-up. At the end of the observation period, a satisfactory pain control was reported in both groups, although with a statistically and clinically significant advantage of the M group. Also, a clinically (< 30%) and highly meaningful (< 50%) pain reduction was found more frequently in the M group. The general condition of patients based on the ESAS overall symptom score was better in the M group with a median score of 10 versus 19 (p < 0.001). Forty-one patients in WO switched to a strong opioid (35%) and 17 patients (15%) in the M group switched to another strong opioid (p = 0.001).

Conclusions

In patients with cancer and moderate pain (4–6 out of 10), low-dose morphine reduced pain intensity significantly compared to weak opioids (tramadol or codeine) with a similarly good tolerability and adverse effects.

Limitations

  • Risk of bias (no control group)
  • Risk of bias (no blinding)
  • Key sample group differences that could influence results
  • Long accrual of patients
  • Open-label design

Nursing Implications

This study is has very important patient and nursing implications. By not using step II, weak opioids, we could potentially have better control of our patient’s pain as well as decrease costs by not using some of the more expensive weak opioids. More research is needed to compare the most commonly used strong opioids as first-line medications for pain intensity and adverse effects. Future studies should prospectively determine the morphine equivalent daily doses. These studies may determine that step II opioids are less effective and more costly. Ending step II in the World Health Organization's (WHO) ladder could simplify pain management while giving better pain control in a more efficient manner.