Trial Management Group
SC.23 Meets Its Monthly Target Accrual
|SC.23 (A Phase III Double-Blind Study of Dexamethasone versus Placebo in the Prophylaxis of Radiation-Induced Pain Flare Following Palliative Radiotherapy for Bone Metastases) met its monthly target accrual in June 2011 after local activations were started in May. In June, 10 patients were accrued by five different centres. As of July 14, 2011, 14 patients have been entered. We extend our thanks and appreciation to the investigators, CRAs, pharmacists and all other team members that contributed to such a successful start to accrual for this study.
* Accrual and activations as of 2011-Jul-14
SC.23 is a trial that was built on the strong pilot data generated by the research team led by the SC.23 study chair, Edward Chow at the Toronto Sunnybrook Odette Cancer Centre. Pain flare is a known side effect of palliative radiotherapy for bony metastases; however, its frequency was poorly documented and varying definitions and timing of assessment hampered direct comparison of reports (1). Chow's group used published definitions of pain progression to develop a definition of pain flare and performed two multicentre pilot studies that documented both the timing and incidence of pain flare in patients treated with both single fraction (8 Gy) and multiple fraction (20 Gy in five fractions or 30 Gy in ten fractions) palliative radiotherapy (2; 3). In patients treated with single fraction therapy, the incidence ranged from 14% (2) to 39% (3) and the vast majority of pain flares occurred in the first five days after radiation therapy. The severe impact of pain flare on patient function was documented by interviewing a subset of 13 patients from the second pilot study (4). Although more than three-quarters of patients took additional analgesics to manage the increased pain, 90% of those patients were not able to achieve adequate pain control. Almost 85% of patients explicitly stated that they would have preferred prevention of pain flare as opposed to treatment with additional analgesics.
Dexamethasone is a synthetic glucocorticoid used as an anti-inflammatory or immunosuppressive agent. It is postulated that pain flare following external beam irradiation to painful bone metastases is a result of an inflammatory process in predisposed individuals. Chow's group conducted a pilot study to investigate the efficacy of a single 8 mg dose of dexamethasone given at least one hour prior to radiotherapy to prevent pain flare in patients receiving a single fraction 8 Gy treatment for bone metastases and demonstrated a pain flare incidence of 24% without reports of dexamethasone-related adverse effects or functional interference (5). Based on when the pain flares occurred, the investigators identified the potential benefit of additional doses of dexamethasone. Another multicentre pilot study was performed using an 8 mg dose of dexamethasone given one hour prior to single fraction radiotherapy and in the morning daily for three days following treatment (6). The incidence of pain flare was 22% and no dexamethasone-related adverse events were reported.
The success of the use of dexamethasone for prophylaxis of radiation-induced pain flare in these pilot studies led to the development of the dosing schedule for SC.23: a single 8 mg dose of dexamethasone or placebo given at least one hour prior to a single 8 Gy fraction of palliative radiation therapy, followed by 8 mg daily on each of the five mornings fol or pain flare (using the definition developed by Chow's group) and adverse events for ten days after radiotherapy. In addition, urine samples are collected pre- and post-treatment at a subset of participating centres to further investigate the role of inflammatory cytokines in pain flare and its prophylaxis by dexamethasone. Failure of dexamethasone to prevent pain flare is hypothesized to be related to rapid drug metabolism, glucocorticoid receptor defects and single nuclear polymorphisms (SNPSs). This will be explored using DNA obtained from saliva samples from patients enrolled at participating centres.
1. Wu J, Wong R, Johnston M, et al. Meta-analysis of dose-fractionation radiotherapy trials for the palliation of painful bone metastases. Int J Radiat Oncol Biol Phys 2003; 55:594.
2. Chow E, Ling A, Davis L, et al. Pain flare following external beam radiotherapy and meaningful change in pain scores in the treatment of bone metastases. Radiother Oncol 2005; 75:64.
3. Hird A, Chow E, Zhang L, et al. Determining the incidence of pain flare following palliative radiotherapy for symptomatic bone metastases: results from three Canadian cancer centres. Int J Radiation Oncology Biol Phys 2009; 75:193.
4. Hird A (c), Wong R, Flynn C, et al. Impact of pain flare on patients treated with palliative radiotherapy for symptomatic bone metastases. J Pain Manag 2009; 2:401.
5. Chow E, Loblaw A, Harris K et al. Dexamethasone for the prophylaxis of radiation-induced pain flare after palliative radiotherapy for bone metastases¿a pilot study. Support Care Cancer 2007; 15:643.
6. Hird A, Zhang L, Holt T, et al. Dexamethasone for the prophylaxis of radiation-induced pain flare following palliative radiotherapy for symptomatic bone metastases: A phase II study. Clin Oncol (R Coll Radiol) 2009; 21:329.