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| 1 | Vemurafenib改善伴BRAF V600E突变的黑色素瘤患者的生存率显示文摘背景 BRAF激酶抑制剂vemurafenib(PLX4032)的1期和2期临床试验已证实其对伴BRAFV600E突变的转移性黑色素瘤患者的反应率超过50%。方法我们在675例既往未经治疗、伴BRAFV600E突变的转移性黑色素瘤患者中,实施了一项Ⅲ期随机化临床试验以比较vemurafenib和Dacarbazine(氮烯唑胺)。患者通过随机分配,分别接受vemurafenib(每次口服960mg,每天两次)或氮烯唑胺(每3周静脉注射1000mg·m-2体表面积)。本研究主要终点是比较总体生存率及无进展期生存率。次要终点包括反应率、反应持续时间以及安全性。计划在死亡98例患者时进行中期分析、死亡196例时进行最终分析。结果在治疗6个月后,vemurafenib组总体生存率为84%(95%置信区间[CI],78-89),而氮烯唑胺组为64%(95%CI,56-73)。在对总体生存率的中期分析及无进展期生存率的最终分析中,与氮烯唑胺相比,vemurafenib能相对减低63%的死亡风险,以及减低74%的死亡或者疾病进展风险(两种比较P<0.001)。通过数据及安全监督委员会进行独立中期分析审查后,建议氮烯唑胺组患者也转而服用vemurafenib。对Vemurafenib反应率是48%而氮烯唑胺只有5%。伴Vemurafenib常见不良反应为关节痛、皮疹、疲劳、脱发、角化棘皮瘤或鳞状细胞癌、光过敏、恶心和腹泻;38%的患者因为毒副作用要求调整剂量。结论 Vemurafenib能改善既往未经治疗、伴有BRAFV600E突变的黑色素瘤患者的总体及无进展期生存率。(本研究由瑞士罗氏制药有限公司资助;BRIM-3临床试验编号:NCT01006980) | 涂超 Chapman PB Hauschild A Robert C | 2011 | 肿瘤药学2011，1，5： | 2 |
| 2 | The 5-HT (7) receptor in learning and memory 显示文摘 | Roberts A J Hedlund PB | 2012 | Hippocampus2012，22，4： | 1 |
| 3 | Improved survival with vemurafenib in melanoma with BRAF V600E mutation 显示文摘 | Chapman PB Hauschild A Robert C | 2011 | N Engl J Med2011，364，： | 1 |
| 4 | Improved survival with vemurafenib in melanoma with BRAF V600E mutation 显示文摘 | Chapman PB Hauschild A Robert C | 2011 | N Engl J Med2011，364，26： | 1 |
| 5 | Improved sur-viral with vemurafenib in melanoma with BRAF V600E muta- tion 显示文摘 | Chapman PB Hauschild A Robert C | 2011 | N Engl j Med2011，364，26： | 1 |
| 6 | Improved survival with vemurafenib in melanoma with BRAF V600E mutation显示文摘 | Chapman PB Hauschild A Robert C | 2011 | N Engl J Med2011，364，26： | 1 |
| 7 | Bone mineral densi-ty correlates with fracture load in experimental side impactsof the pelvis显示文摘 | David PB Greg JD Robert RL | 2003 | J Biomech2003，36，2： | 1 |
| 8 | Rhabdomyolysis associated with infection by mycoplasa pneumoniae:a case report显示文摘 | Rachel PB Robert MW | 2000 | Pediatrics2000，105，2： | 1 |
| 9 | Presenting D-di- mer and ear|y symptom severity are independent predictors for post- thrombotic syndrome following a first deep vein thrombosis 显示文摘 | ROBERTS LN PATEL RK CHITONGO PB | 2013 | Br J Haematol2013，160，6： | 1 |
| 10 | Rhabdomyolysis associated with infection bymycoplasma pneumouiae: a case report显示文摘 | Rachel PB Robert MW | 2000 | Pediatric2000，105，2： | 1 |
| 11 | Podocyte expression of hypoxia inducible factor (HIF) 1 and HIF 2 during glomerular development显示文摘 | Freeburg PB Robert B Abrahamson DR | 2003 | J Am Soc Nephrol2003，14，： | 1 |
| 12 | Improved survival with vemurafenib in melanoma with BRAF V600E mutation显示文摘 | Chapman PB Hauschild A Robert C | 2011 | N Engl J Med2011，364，26： | 1 |
| 13 | Improved survival with vemurafenib in melanoma with BRAF V600E rnutation显示文摘 | CHAPMAN PB HAUSCHILD A ROBERT C | 2011 | N EnglJ Med2011，364，26： | 1 |
| 14 | Linking outcomes measurement to continual improvementthe serial V way of thinking about improving clinical care显示文摘 | Nelson EC Roberts JS | 1994 | Jt Comm J Qual Improv1994，20，： | 1 |
| 15 | Improved survival with vemurafenib in melanoma with BRAF V600E mutation显示文摘 | Chapman PB Hauschild A Robert C | 2011 | N Engl J Med Jun2011，364，26： | 1 |
| 16 | Rhabdomyolysis associated with infection by mycoplasma pneumoniae: A case report 显示文摘 | Rachel PB Robert MW | 2000 | Pediatrcs2000，105，2： | 1 |
| 17 | Podocyte expression of hypoxia-inducible factor (HIF)-1 and HIF-2 during glomerular development显示文摘 | Freeburg PB Robert B St John PL | 2003 | J Am Soc Nephrol2003，14，4： | 1 |
| 18 | Improved survival with vemurafenib in melanoma with BRAF V6OOE mutation显示文摘 | Chapman PB Hauschild A Robert C | 2011 | N Engl J Med2011，364，26： | 1 |
| 19 | The 5-HT(7)receptor in learning memory显示文摘 | Roberts AJ Hedlund PB | 2012 | Hippocampus2012，22，4： | 1 |
| 20 | Phase Ⅲ randomized,open-label,multicenter trial (BRIM3) comparing BRAF inhibitor vemurafenib with dacarbazine (DTIC) in patients with V600EBRAF-mutated melanoma显示文摘 | Chapman PB Hauschild A Robert C | | 0，，： | 1 |
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