Chemoradiation With Capecitabine for Palliation of Pain From Bone Metastasis

BACKGROUND

Much of the clinical practice of oncology involves palliative care. In this setting ,the emphasis is on alleviation of symptoms and preservation or improvement of quality of life. A large body of clinical evidence documents the effectiveness of local-field external beam radiotherapy in palliation of pain from osseous metastases (1). Despite this general agreement, controversy remains regarding the optimal dose and fractionation schedule. Prospective phase III clinical trials (2-6), today, have failed to demonstrate superiority of one schedule over another ,and as a result, the patterns of practice of remain diverse in duration and intensity.

Between 1974 and 1980 the RTOG conducted a large national study to determine the effectiveness of five different dose fractionation schedules(2). A total of 1016 patients were entered ,266 into a "solitary metastasis" stratum, and 750 into a "multiple metastasis " stratum. The former were randomly assigned to treatment with 40,5Gy in 15 fractions or 20Gy in 5 fractions. The latter were assigned to 30Gy in 10 fractions, 15 Gy in5 fractions ,20 Gy in 5 fractions, or 25 Gy in 5 fractions. A quantitative measure of pain ,based on severity and frequency of pain, and the type and frequency of pain medications used, was devised to evaluate response. Overall, 89% of patients experienced minimal relief. There were no significant difference between the treatment arms in both strata. The initial pain score was found to be a useful predictor ; patients with high score were less likely to respond and were less likely to experience a complete response. Patients with breast and prostate cancer were significantly more likely to respond than patients with lung or other primary lesions. Patients completing their treatment as planned had significantly higher rates of complete response than those who did not .While some relief was experienced almost invariably within the first four weeks, complete relief was first reported later than four weeks after start of treatment in about 50 % of patients .The median duration of minimal and complete pain relief was 20 and 12 weeks ,respectively. There were no significant differences in duration of pain relief between the different arms It was concluded that all treatment dose schedules were equally effective.

A reanalysis of the RTOG study was reported by Blitzer (7).Using a stepwise logistic regression, he examined the effect of the number of fractions, the dose per fraction, and solitary versus multiple metastases, on the probability of attaining complete pain relief and the need for retreatment. This multivariate technique allowed patients with solitary and multiple metastases to be analyzed together. By increasing the number of subjects and events the statistical power of the analysis was outcome. There was no correlation of the time dose factor with outcome (8). It was concluded that the more protracted schedules resulted in improved pain relief.

Price et al. randomized 288 patients to receive either 8 Gy in one fraction or 30 Gy in 10 daily fractions. Pain was assessed using a questionnaire completed by the patients at the home on a daily basis. No differences were found in the probability of attaining pain relief, the speed of onset or the duration of relief between the two arms(4). Hoskin et al. randomized 270 patients to receive either 4 Gy or 8 Gy in one fraction (3) Pain assessed by the patient) and analgesic usage were recorded before treatment and at 2,4,8 and 12 weeks. At 4 weeks the response rates were 69% for 8 Gy and 44% for 4 Gy (p<0.001). The duration of the effect was independent of dose.