OBJECTIVE: To assess the efficacy and safety of pentoxifylline, a US Food and 
Drug Administration-approved drug, in patients with ALS treated with riluzole.
METHODS: The authors conducted a double-blind, randomized, placebo-controlled, 
multicenter trial. Four hundred patients with probable or definite ALS and vital 
capacity less than 100% were randomly assigned to treatment with placebo or 1.2 
g pentoxifylline daily. The primary outcome was death. Secondary outcomes were 
rates of deterioration of ALS Functional Rating Scale-Respiratory and muscle 
strength. The primary intention-to-treat analysis was the survival comparison of 
drug vs placebo, assessed before (log-rank test) and after adjustment (Cox 
model) for predefined prognostic factors.
RESULTS: At the end of the study, after 547 days of follow-up, 103 patients 
(51.7%) in the pentoxifylline group and 120 (59.7%) in the placebo group were 
alive (unadjusted risk 1.28, p = 0.107; adjusted risk 1.43, p = 0.02). In 
contrast, analysis of secondary outcome functional variables did not show the 
same negative effect of the drug. The most common adverse reactions were nausea, 
dysphagia, and flushing, all reversible after stopping the drug.
CONCLUSIONS: Pentoxifylline is not beneficial in ALS and should be avoided in 
patients treated with riluzole. The discrepancy between survival and measures of 
functional changes urges caution in equating these end points in phase III 
trials, and suggests that both survival and function should be used in phase III 
trials.