Martin-Broto, J., Cleeland, C.S., Glare, P.A., Engellau, J., Skubitz, K.M., Blum, R.H., . . . Atchison, C. (2014). Effects of denosumab on pain and analgesic use in giant cell tumor of bone: Interim results from a phase II study. Acta Oncologica, 53, 1173–1179.

DOI Link

Study Purpose

To describe the effect of denosumab on pain and analgesic use in patients with giant cell tumor of bone (GCTB)

Intervention Characteristics/Basic Study Process

Patients were split into two groups, cohort 1, which contained patients with unresectable disease or multiple lesions, and cohort 2, which contained patients with resectable disease but for whom surgery was associated with high morbidity. Patients received denosumab every four weeks with additional doses on days 8 and 15. Pain was assessed with the Brief Pain Inventory Short Form at baseline and each visit for the first six months and every three months thereafter.

Sample Characteristics

  • N = 271  
  • AVERAGE AGE: 33.5 years
  • MALES: 41%, FEMALES: 59%
  • KEY DISEASE CHARACTERISTICS: Patients had either unresectable disease or had disease associated with high morbidity; ≥ 12 years old with active histologically confirmed GCTB

Setting

  • SITE: Multi-site  
  • SETTING TYPE: Not specified    
  • LOCATION: Multiple international centers

Phase of Care and Clinical Applications

  • PHASE OF CARE: Mutliple phases of care
  • APPLICATIONS: Elder care and palliative care 

Study Design

  • Phase II, prospective clinical trial

Measurement Instruments/Methods

  • The Brief Pain Inventory Short Form (BPI-SF) was used to evaluate pain and minimally important differences.
  • The Analgesic Quantification Algorithm (AQA) was used to evaluate analgesic use at each visit.

Results

Cohort 1: Moderate to severe pain was reported in 45% of patients with strong opioid use in 33% of patients at baseline. The median time to a clinically relevant decrease in pain was 30 days (CI = 95%, SD = 16–57). The estimated median time to a clinically relevant pain worsening was 23.3 months, and 39% of patients (56) reduced strong opioid use to little or no use. Less than 5% of patients with no or low use at baseline (113) shifted to strong opioid use.
 
Cohort 2: Moderate to severe pain was report in 49% of patients with strong opioid use in 14% of patients at baseline. The median time to a clinically relevant decrease in pain was 30 days (CI = 95%, SD = 15–29). The estimated median time was not determined for worsening pain for cohort 2 because a small number of patients (16/89) experienced pain worsening during the study, with 40% of patients (14) reducing strong opioid use to little or no use. Less than 5.3% of patients with no or low use at baseline (86) shifted to strong opioid use.

Conclusions

Denosumab is a reasonable treatment choice for pain relief in patients with GCTB with unresectable disease, disease with multiple lesions, or for patients in whom resection would be associated with high morbidity. This treatment would reduce radiotherapy-related risks and provide a medical option for treating patients in who  surgical intervention (the treatment of choice) is not a option or is presented as a high-risk option.

Limitations

  • Risk of bias (no control group)
  • Risk of bias (no blinding)
  • Risk of bias (no random assignment)

Nursing Implications

Denosumab is an easy drug to administer that has few side effects. Education on the drug and its administration would be required to effectively treat patients limited to this option. Nurses could help advocate for patients with unresectable disease or disease associated with high morbidity with surgery. This could be an alternative to radiation if patients are unable to receive radiation or are concerned about the low but present risk of secondary tumors from radiation treatment.