Fotemustine compared with dacarbazine in patients with disseminated malignant melanoma:: A phase III study
Fotemustine compared with dacarbazine in patients with disseminated malignant melanoma:: A phase III study
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DOI：
10.1200/jco.2004.04.165
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发表时间：
2004-03-15
影响因子：
45.3
通讯作者：
Menu, Y
中科院分区：
文献类型：
--
作者：
Avril, MF;Aamdal, S;Menu, Y
目的比较福替莫司汀和达卡巴津(DTIC)作为主要终点的总缓解率(ORR)和总存活率、反应持续时间、进展时间、脑转移(BM)发生时间的差异，并评价其安全性和生活质量。非进展期患者每4周接受一次维持治疗(福替莫司汀100 mg/m(2)或DTIC 250 mg/m(2)，共5天)。结果229例患者随机分为福替莫司汀或DTIC组。在意向治疗人群中，福替莫司汀组的最佳ORR高于DTIC组(n=229；15.2%vs6.8%，P=.043)和全分析组(n=221)(15.5%vs7.2%，P=.053)。观察到相似的中位缓解期(福替莫司汀5.8个月与DTIC 6.9个月)和进展时间(1.8个月与1.9个月)。在纳入时未出现骨髓的患者中，福替莫司汀治疗后达到骨髓抑制的中位时间为22.7个月，而DTIC为7.2个月(P=0.059)。福替莫司汀的中位生存期为7.3个月，DTIC为5.6个月(P=0.067)。主要毒副反应为3~4级中性粒细胞减少症(福替莫司汀为51%，DTIC为5%)和血小板减少症(43%，6%)。两组患者的生活质量无显著差异。结论在播散性黑色素瘤的一线治疗中，福替莫司汀组的ORR高于DTIC组。在总体存活率和BM时间方面，福替莫司汀的趋势是明显的。
PurposeTo compare fotemustine and dacarbazine (DTIC) in terms of overall response rate (ORR) as primary end-point and overall survival, duration of responses, time to progression, time to occurrence of brain metastases (BM), and to assess safety and quality of life in patients with disseminated cutaneous melanoma.Patients and MethodsPatients received either intravenous fotemustine 100 mg/m(2) weekly for 3 weeks or DTIC 250 mg/m(2)/d for 5 consecutive days every 4 weeks (two cycles). Nonprogressive patients received a maintenance treatment every 4 weeks (fotemustine 100 mg/m(2) or DTIC 250 mg/m(2) for 5 days).ResultsTwo hundred twenty-nine patients were randomly assigned to fotemustine or DTIC arms. The best ORR was higher in the fotemustine arm than in the DTIC arm in the intent-to-treat population (n = 229; 15.2% v 6.8%, P = .043) and in full analysis set (n = 221) (15.5% v 7.2%, P = .053). Similar median durations of responses (5.8 months with fotemustine v 6.9 months with DTIC) and time to progression (1.8 v 1.9 months, respectively) were observed. In patients without BM at inclusion, the median time to BM was 22.7 months with fotemustine versus 7.2 months with DTIC (P = .059). Median survival was 7.3 months with fotemustine versus 5.6 months with DTIC (P = .067). The main toxicity was grade 3 to 4 neutropenia (51% with fotemustine v 5% with DTIC) and thrombocytopenia (43% v 6%, respectively). No significant difference was noted for quality of life between arms.ConclusionORR was higher in the fotemustine arm compared to the DTIC arm in first-line treatment of disseminated melanoma. A trend in favor of fotemustine in terms of overall survival and time to BM was evidenced.