Kundel, Y., Nasser, N.J., Purim, O., Yerushalmi, R., Fenig, E., Pfeffer, R.M., . . . Brenner, B. (2013). Phase II study of concurrent capecitabine and external beam radiotherapy for pain control of bone metastases of breast cancer origin. PloS One, 8, e68327. 

To test the safety and efficacy of treatment with localized radiotherapy and capecitabine for management of painful bone metastases

Women with bone metastases from breast cancer received radiation with 30Gy in 10 fractions to cover all metastatic bone regions, given 5 days per week.  Oral capecitabine at 1400mg/m² was given 5 days per week, concurrently with radiation therapy.  Patients were evaluated weekly during treatment and for every 4 weeks after treatment, for a total of 12 weeks after completion of treatment.

• N = 29  
• MEDIAN AGE = 59 years (range = 35–84 years)
• FEMALES: 100%
• KEY DISEASE CHARACTERISTICS: All patients had one to three areas of bone metastases from breast cancer.
• OTHER KEY SAMPLE CHARACTERISTICS: Eleven patients were also on bisphosphonates.

• SITE: Single-site    
• SETTING TYPE: Outpatient    
• LOCATION: Israel

• PHASE OF CARE: Late-effects and survivorship
• APPLICATIONS: Palliative care 

Phase-II, observational study

• National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI's CTCEA) version 3
• Pain intensity evaluated on four-point scale 
• Side effects graded on 0–4 scale
• Analgesic consumption graded on a five-point World Health Organization (WHO) scale
• Response graded according to International Bone Metastases Consensus grading

Side effects were mild. The most prevalent were nausea (33%), diarrhea (24%), weakness (21%), and mucositis (10%). The mean pain score decreased from 2.93 to 2.28 after one week (p < .002), to 1.45 after two weeks (p < .0001), and to 1.14 after four weeks (p < .01). Changes in pain scores after four weeks were not significant. Declines in analgesic use were noted during the first four weeks of treatment (p < .02) and were stabilized thereafter. The response rate was 31% at one week and 38% at 12 weeks. There were no differences between patients who did and did not receive bisphosphonates.

Combined radiation therapy with capecitabine was effective for the short-term reduction on pain from bone metastases with relatively mild side effects in the majority of subjects.

• Small sample (< 30)
• Risk of bias (no control group)
• Risk of bias (no blinding)
• Risk of bias (no random assignment)
• Other limitations/explanation: No information was provided regarding pain medications used or pain duration.

Combined radiation therapy and capecitabine may be a promising intervention for the palliation of painful bone metastases. Further research is needed to fully determine its efficacy and toxicity.