晚期肺癌的维持治疗2vfjqcrp.ppt

* * * * * * * * Background： Palliation of disease-related symptoms is an important clinical benefit. For advanced disease，this may be relief or delay of worsening of symptoms. Since benefit evaluation in clinical trials is usually focused on radiological assessments，development is needed to establish symptom improvement as an efficacy endpoint. Methods： To determine if gem maintenance therapy delayed the worsening of symptoms，retrospective analyses were performed using symptom data reported by patients (pts) with advanced NSCLC from a randomized trial of gem plus cisplatin followed by gem maintenance therapy plus best supportive care (GBSC) or best supportive care (BSC) (Krzakowski，ASCO 2004). Pts rated 6 symptoms using the Lung Cancer Symptom Scale (LCSS) at baseline and every cycle. Symptom worsening was retrospectively defined as a 15-mm increase in the severity score for any symptom (based on 100-mm scales) from randomization (start of maintenance therapy). Analyses were repeated for 10- and 20-mm increases. Data were analyzed using Kaplan-Meier (KM) plots and Cox regression，with censoring at the last LCSS for pts with no worsening. Results： At randomization，73% were stage IV and 48% had Karnofsky performance status 80. Of the 206 pts randomized，171 were included in the symptom analyses. Although not significant，the KM plot for TWS based on the 15-mm definition (defn) showed a separation between arms in favor of GBSC beginning ~2.5 months after randomization (p = 0.24，HR = 0.79). TWS results for the 20-mm defn were significant in favor of GBSC (p = 0.013，HR = 0.59). When the same analysis was applied to individual symptoms，all symptoms showed the same numerical trend (HR0.77) in favor of GBSC，with significant TWS advantage for GBSC (HR0.56) for appetite loss and fatigue (15- and 20-mm defn) and for pain (20-mm defn). Additional analyses suggested a strong correlation between TWS and time to progressive disease. Conclusions： In addition to prolonging time to dise