In a phase III trial in patients with castration-resistant prostate cancer (CRPC) and bone metastases, denosumab was superior to zoledronic acid in reducing skeletal-related events (SREs; radiation to bone, pathologic fracture, surgery to bone, or spinal cord compression). This study reassessed the efficacy of denosumab using symptomatic skeletal events (SSEs) as a prespecified exploratory end point. Patients with CRPC, no previous bisphosphonate exposure, and radiographic evidence of bone metastasis were randomized to subcutaneous denosumab 120 mg plus i.v. placebo every 4 weeks (Q4W), or i.v. zoledronic acid 4 mg plus subcutaneous placebo Q4W during the blinded treatment phase. SSEs were defined as radiation to bone, symptomatic pathologic fracture, surgery to bone, or symptomatic spinal cord compression. The relationship between SSE or SRE and time to moderate/severe pain was assessed using the Brief Pain Inventory Short Form. Treatment with denosumab significantly reduced the risk of developing first SSE [HR, 0.78; 95% confidence interval (CI) 0.66–0.93; P = 0.005] and first and subsequent SSEs (rate ratio, 0.78; 95% CI 0.65–0.92; P = 0.004) compared with zoledronic acid. The treatment differences in the number of patients with SSEs or SREs were similar (n = 48 and n = 45, respectively). Among patients with no/mild pain at baseline, both SSEs and SREs were associated with moderate/severe pain development (P < 0.0001). Fewer patients had skeletal complications, particularly fractures, when defined as SSE versus SRE. In patients with CRPC and bone metastases, denosumab reduced the risk of skeletal complications versus zoledronic acid regardless of whether the end point was defined as SSE or SRE.

Purpose: Tasquinimod, a novel oral therapy targeting the tumor microenvironment, significantly improved progression-free survival (PFS) in a randomized, placebo-controlled phase II trial in men with metastatic castration-resistant prostate cancer (mCRPC). This phase III study was conducted to confirm the phase II results and to detect an overall survival (OS) benefit. Patients and Methods: Men with chemotherapy-naïve mCRPC and evidence of bone metastases were assigned (2:1) to receive tasquinimod once per day or placebo until progression or toxicity. The primary end point was radiographic PFS (rPFS; time from random assignment to radiologic progression or death) per Prostate Cancer Working Group 2 criteria and RECIST 1.1. The study had 99.9% power to detect an rPFS hazard ratio (HR) of 0.6 with a two-sided alpha error of .05 and 80% power to detect a target HR of 0.8 for OS, the key secondary end point. Results: In all, 1,245 patients were randomly assigned to either tasquinimod (n = 832) or placebo (n = 413) between March 2011 and December 2012 at 241 sites in 37 countries. Baseline characteristics were balanced between groups: median age, 71 years; Karnofsky performance status ≥ 90%, 77.3%; and visceral metastases, 21.1%. Estimated median rPFS by central review was 7.0 months (95% CI, 5.8 to 8.2 months) with tasquinimod and 4.4 months (95% CI, 3.5 to 5.5 months) with placebo (HR, 0.64; 95% CI, 0.54 to 0.75; P < .001). Median OS was 21.3 months (95% CI, 19.5 to 23.0 months) with tasquinimod and 24.0 months (95% CI, 21.4 to 26.9 months) with placebo (HR, 1.10; 95% CI, 0.94 to 1.28; P = .25). Grade ≥ 3 adverse events were more frequent with tasquinimod (42.8% v 33.6%), the most common being anemia, fatigue, and cancer pain. Conclusion: In chemotherapy-naïve men with mCRPC, tasquinimod significantly improved rPFS compared with placebo. However, no OS benefit was observed.

Painful bone metastases are most frequent in patients with advanced prostate or breast carcinoma. The aim of this study was to compare the analgesic effect of radionuclide therapy using Sr and Sm-EDTMP in patients with painful bone metastases of these tumours. One hundred patients treated with radionuclide bone palliation therapy were analysed. The study population consisted of 60 male patients with advanced prostate carcinoma and 40 female patients with advanced breast carcinoma. Fifty patients (30 men and 20 women) were treated with Sr (150 MBq). The other 50 patients were treated with Sm-EDTMP (37 MBq x kg). The treatment efficacy was evaluated by a visual analogue scale (VAS), Karnofsky performance scale, and dosage of analgesic drugs used. Complete pain relief was found in 40% of women and 40% of men treated using Sm-EDTMP and in 25% of women and 33% of men treated with Sr. No analgesic effect occurred in 20% of patients. A better analgesic effect was found in cases of osteoblastic metastases compared to mixed metastases. Statistically significant reduction of pain intensity, use of analgesic drugs and improvement of performance in Karnofsky scale was found in cases of both radionuclides. The analgesic effects of Sr and Sm-EDTMP was similar in both prostate and breast carcinoma. However, the effect was dependent on the type of metastases; better response was observed in cases of osteoblastic metastases than in patients with mixed metastases. Severe adverse reactions after this therapy were rare.

Total skin electron irradiation (TSEI) has been employed as one of the methods of mycosis fungoides treatment since the mid-twentieth century. In order to improve the effects and limit the complications following radiotherapy, a number of varieties of the TSEI method, frequently differing in the...