Implications of the 5-year CR FIRST trial. Sinemet CR Five-Year International Response Fluctuation Study.

Almost since the introduction of levodopa for Parkinson's disease (PD), its side effects have concerned clinicians. One strategy to avoid side effects has been to delay levodopa therapy; an alternative has been to use early therapy but to avoid fluctuations in plasma levodopa levels. This latter strategy led to the development of sustained-release carbidopa-levodopa, which was compared with immediate-release carbidopa-levodopa in the CR Five-Year International Response Fluctuation Study (FIRST), a 5-year multicenter study of early, levodopa-naive PD patients. The incidence of motor fluctuations was lower than expected for both groups, and patients receiving sustained-release carbidopa-levodopa fared better on the activities of daily living portion of the Unified Parkinson's Disease Rating Scale and on portions of the Nottingham Health Profile. The trial demonstrated the value of low-dose therapy, the lack of toxicity of this low-dose approach over 5 years in early PD.