Comparison of high-dose methotrexate (HDMTX) toxicity in elderly and younger patients (pts) with primary central nervous system lymphoma (PCNSL)

Abstract

8041 Background: A reduced dose of HDMTX is often given to elderly pts because of the risk of toxicity. This may result in loss of treatment efficacy and further prognosis impairment in this poor prognosis population. Methods: HDMTX toxicity was prospectively evaluated in an ongoing randomized multicenter phase IV study in PCNSL pts. In 154 pts, an analysis of toxicity according to the pts' age was performed. Median age was 61 years (yrs). Sixty-five pts were ≤ 60 yrs and had a median Karnofsky performance score (KPS) of 80, 89 pts were > 60 yrs and had a median KPS of 70. HDMTX (4 g/m2 per course) was administered as a 4-hour intravenous (IV) infusion on day 1 every 2 weeks for a maximum of 6 courses and was accompanied by IV hydration, urinary alkalinization, and leucovorin rescue at a dose of 30 mg IV every 6 hours after 24 hours of HDMTX infusion. HDMTX dose reduction was performed according to creatinine clearance values evaluated before each treatment course: the percentage of dose reduction equaled the percentage of creatinine clearance value below 100 ml/min. Results: Toxicity was generally mild to moderate. No statistically significant differences in frequency and severity of toxicity between pts ≤ 60 and > 60 yrs were noted (table). No therapy-related deaths occurred. Dose reduction due to decrease in creatinine clearance was much more frequent in pts > 60 yrs than in those ≤ 60 yrs (43.9 % versus 17.5 %, p = 0.001). Conclusions: HDMTX is safe regardless of age when dose reduction is performed according to creatinine clearance. Dose reduction solely according to age does not appear to be justified. No significant financial relationships to disclose.