Bcl-2 antisense (oblimersen sodium) plus dacarbazine in patients with advanced melanoma: The oblimersen melanoma study group
Bcl-2 antisense (oblimersen sodium) plus dacarbazine in patients with advanced melanoma: The oblimersen melanoma study group
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DOI：
10.1200/jco.2006.06.0483
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发表时间：
2006-10-10
影响因子：
45.3
通讯作者：
Haluska, Frank G.
中科院分区：
文献类型：
--
作者：
Bedikian, Agop Y.;Millward, Michael;Haluska, Frank G.
目的黑色素瘤化疗耐药与Bcl-2蛋白介导的抗凋亡作用有关。我们评估了是否使用反义寡核苷酸靶向Bcl-2，奥力默森钠可提高晚期黑色素瘤患者全身化疗的疗效。患者和方法我们将未经化疗的晚期黑色素瘤患者随机分配至达卡巴嗪治疗组（1，000 mg/m2）单独给药或在此之前连续5天静脉输注奥利默森钠（7 mg/kg/d），每3周一次，最多8个周期。患者按东部肿瘤协作组体力状态、肝转移、疾病部位和血清乳酸脱氢酶（LDH）分层。结果在随机分配的771例患者中，在达卡巴嗪基础上加用奥力默森治疗，在24个月最短随访时有改善生存率的趋势（中位数，9.0 v7.8个月; P = 0.077），无进展生存率显著增加（中位数，2.6 v1.6个月; P
PurposeChemotherapy resistance in melanoma has been linked to antiapoptotic effects mediated by Bcl-2 protein. We evaluated whether targeting Bcl-2 using an antisense oligonucleotide (oblimersen sodium) could improve the efficacy of systemic chemotherapy in patients with advanced melanoma.Patients and MethodsWe randomly assigned chemotherapy-naive patients with advanced melanoma to treatment with dacarbazine ( 1,000 mg/m(2)) alone or preceded by a 5-day continuous intravenous infusion of oblimersen sodium ( 7 mg/kg/d) every 3 weeks for up to eight cycles. Patients were stratified by Eastern Cooperative Oncology Group performance status, liver metastases, disease site, and serum lactate dehydrogenase (LDH). The primary efficacy end point was overall survival.ResultsAmong 771 patients randomly assigned, the addition of oblimersen to dacarbazine yielded a trend toward improved survival at 24-month minimum follow-up ( median, 9.0 v 7.8 months; P =.077) and significant increases in progression-free survival ( median, 2.6 v 1.6 months; P