Wendy Seiferheld

PURPOSE: Primary CNS lymphoma (PCNSL) is an aggressive primary brain tumor. Cranial irradiation alone rarely results in long-term disease control or prolonged survival. We prospectively studied the use of combination chemotherapy plus cranial irradiation in newly diagnosed patients with PCNSL. PATIENTS AND METHODS: We enrolled 102 newly diagnosed, immunocompetent patients with PCNSL; 98 were assessable. Patients first received five cycles of methotrexate 2.5 g/m(2), vincristine, procarbazine, and intraventricular methotrexate (12 mg). Whole-brain radiotherapy (RT) was administered to a total dose of 45 Gy and all patients received high-dose cytarabine after RT. RESULTS: Fifty-eight percent of patients with measurable disease had a complete response to preirradiation chemotherapy and 36% had a partial (> 50%) response, for a 94% response rate. Median progression-free survival was 24.0 months and overall survival was 36.9 months. Age was an important prognostic factor; median survival was 50.4 months in patients younger than 60 and only 21.8 months in those aged 60 or older (P <.001). Fifty-three percent of patients had grade 3 or 4 toxicity during induction chemotherapy, half of which was hematologic. However, 12 patients (15%) experienced severe delayed neurologic toxicity, eight of whom died. CONCLUSION: This is the first multicenter trial demonstrating improved survival with the combination of chemotherapy plus RT compared with previous reports of RT alone. A high-dose methotrexate-based regimen produced a high response rate before RT was administered. High-dose methotrexate combined with cranial irradiation is an effective therapeutic approach to PCNSL, but neurotoxicity is a delayed risk of this approach.

BACKGROUND: Salvage radiation therapy is often necessary in men who have undergone radical prostatectomy and have evidence of prostate-cancer recurrence signaled by a persistently or recurrently elevated prostate-specific antigen (PSA) level. Whether antiandrogen therapy with radiation therapy will further improve cancer control and prolong overall survival is unknown. METHODS: In a double-blind, placebo-controlled trial conducted from 1998 through 2003, we assigned 760 eligible patients who had undergone prostatectomy with a lymphadenectomy and had disease, as assessed on pathological testing, with a tumor stage of T2 (confined to the prostate but with a positive surgical margin) or T3 (with histologic extension beyond the prostatic capsule), no nodal involvement, and a detectable PSA level of 0.2 to 4.0 ng per milliliter to undergo radiation therapy and receive either antiandrogen therapy (24 months of bicalutamide at a dose of 150 mg daily) or daily placebo tablets during and after radiation therapy. The primary end point was the rate of overall survival. RESULTS: The median follow-up among the surviving patients was 13 years. The actuarial rate of overall survival at 12 years was 76.3% in the bicalutamide group, as compared with 71.3% in the placebo group (hazard ratio for death, 0.77; 95% confidence interval, 0.59 to 0.99; P=0.04). The 12-year incidence of death from prostate cancer, as assessed by means of central review, was 5.8% in the bicalutamide group, as compared with 13.4% in the placebo group (P<0.001). The cumulative incidence of metastatic prostate cancer at 12 years was 14.5% in the bicalutamide group, as compared with 23.0% in the placebo group (P=0.005). The incidence of late adverse events associated with radiation therapy was similar in the two groups. Gynecomastia was recorded in 69.7% of the patients in the bicalutamide group, as compared with 10.9% of those in the placebo group (P<0.001). CONCLUSIONS: The addition of 24 months of antiandrogen therapy with daily bicalutamide to salvage radiation therapy resulted in significantly higher rates of long-term overall survival and lower incidences of metastatic prostate cancer and death from prostate cancer than radiation therapy plus placebo. (Funded by the National Cancer Institute and AstraZeneca; RTOG 9601 ClinicalTrials.gov number, NCT00002874 .).