• Oncology Clinical Trials
• Radiology
• Reproductive Cancers
• Radiation Therapy

• Oncology
• Oncology Clinical Trials
• Radiology
• Reproductive Cancers
• Radiation Therapy

A phase 3 dose escalation study of radiation therapy (RT) in patients with localized prostate cancer was terminated early and did not find an improvement in the primary outcome of overall survival (OS). The Radiation Therapy Oncology Group 0126 study, presented by Jeff Michalski, MD, Washington University School of Medicine, St Louis, Missouri, USA, found significant improvements in the rates of local control, distant metastases, and biochemical disease-free survival.

The intermediate-risk patients were randomized to a high or low dose of RT (79.2 Gy in 44 fractions, n = 748; 70.2 Gy in 39 fractions, n = 751). They were stratified by Gleason score (GS; 6 vs 7), prostate-specific antigen level (PSA; between 10 and 20 ng/mL vs < 15 ng/mL), and treatment (3D conformal radiation therapy vs intensity-modulated radiotherapy). At baseline, the median age was 71 years, and the tumor stage was T1 and T2 in 57% and 43% of each group, respectively. Most patients (83% of low dose and 85% of high dose) had a GS of 7, and most (70%) had a PSA < 10 ng/mL. Of the low- and high-dose groups, 85% and 83% had a GS 7 and a PSA < 15 ng/mL. The median follow-up was 7.0 years in all patients.

The OS was 66.7% and 65.6% in the high- and low-dose groups, respectively (HR, 0.98; 95% CI, 0.79 to 1.21; log-rank P = .87). Death due to prostate cancer was uncommon, at 13%, while death from other cancer was 22% and other causes, 46%, based on a blinded review. Time to prostate cancer death was similar, at 3.5% and 5.6% in the high- and low-dose groups, respectively (HR, 0.61; 95% CI, 0.33 to 1.11; Gray test, P = .11).

An important and significant difference was seen in biochemical failure at 10 years. Based on the ASTRO consensus definition, it was 30% and 45% in the high- and low-dose groups, respectively (HR, 0.59; 95% CI, 0.49 to 0.70; Gray test, P < .0001), and based on the Phoenix definition, it was 26% and 43%, respectively (HR, 0.59; 95% CI, 0.48 to 0.72; Gray test, P < .0001).

A significant improvement in the rates of local progression and distant metastases was seen at 10 years. With high- versus low-dose RT, the local progression rates were 4% and 8% (HR, 0.42; 95% CI, 0.24 to 0.73; Gray test, P = .0059), and the distant metastasis rates were 5% and 8% (HR, 0.60; 95% CI, 0.37 to 0.98; Gray test, P = .026). Salvage therapy was more common in the low-dose group (20.6% vs 13.5% in the high-dose group; P = .0002).

The rate of acute adverse events was similar in both groups. The incidence of genitourinary (GU) and gastrointestinal (GI) grade 2+ toxicity in the high- and low-dose groups was 2.4% and 2.8% (P = .64) and 11.1% and 12.8% (P = .31), respectively. The incidence of GU plus GI toxicity was 12.3% and 13.7% (P = .42). The rate of late-phase toxicity was higher at 10 years in the high- versus low-dose group (Table 1).

Dr Michalski stated that, compared with the other published trials of dose escalation of RT in patients with prostate cancer, the present trial was the largest by about 2-fold. In all 6 trials, there was no improvement in OS, while there was an improvement in biochemical disease-free survival. The rates of grade 2+ GI toxicity were similar in the late phase in 6 trials, but the rate of GU toxicity was slightly higher in the present study.

• © 2014 MD Conference Express®