A dose-finding and pharmacodynamic study of bortezomib in combination with weekly paclitaxel in patients with advanced solid tumors.
A dose-finding and pharmacodynamic study of bortezomib in combination with weekly paclitaxel in patients with advanced solid tumors.
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DOI：
10.1007/s00280-009-1145-z
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发表时间：
2010-05
影响因子：
3
通讯作者：
Shapiro, Charles L.
中科院分区：
文献类型：
--
作者：
Ramaswamy, Bhuvaneswari;Bekaii-Saab, Tanios;Schaaf, Larry J.;Lesinski, Gregory B.;Lucas, David M.;Young, Donn C.;Ruppert, Amy S.;Byrd, John C.;Culler, Kristy;Wilkins, Diedre;Wright, John J.;Grever, Michael R.;Shapiro, Charles L.
一项确定硼替佐米（B）与每周一次紫杉醇联合治疗晚期实体瘤患者的最大耐受剂量（MTD）的I期研究。合格患者在21天周期的第2天和第9天接受递增剂量的静脉内（IV）硼替佐米（0.6-2 mg/m2），并在第1天和第8天接受100 mg/m2的IV紫杉醇。剂量递增基于两个终点：不超过80%的20 S-蛋白酶体抑制（20-S PI）和剂量限制性毒性（定义为3级或以上非血液学或4级血液学毒性）的发生。45例晚期实体瘤患者接受了318剂硼替佐米和紫杉醇（中位数5，范围1-34），既往化疗方案中位数为3（范围0- 9）。观察到20-S PI的剂量相关抑制，在硼替佐米MTD为1.8 mg/m2时，最大抑制率为70-80%。在MTD（N = 9）时观察到以下毒性：4级中性粒细胞减少症，无发热（n = 2）和脑血管缺血（n = 1）; 3级中性粒细胞减少症（n = 3）、腹泻（n = 2）、恶心（n = 1）和疲乏（n = 1）; 2级疲乏（n = 5）、腹泻（n = 4）和呼吸困难（n = 2）。有1例小汗腺汗孔癌患者部分缓解。在7例（16%）患者中观察到疾病稳定，其中3例为晚期胰腺癌。序贯紫杉醇和硼替佐米在先前治疗的晚期实体瘤患者中产生可接受的毒性，没有相互作用的证据。硼替佐米联合紫杉醇每周一次的II期推荐剂量为1.8 mg/m2。
A phase I study to determine the maximum tolerated dose (MTD) of bortezomib (B) when combined with weekly paclitaxel in patients with advanced solid tumors. Eligible patients received escalating doses of intravenous (IV) bortezomib (0.6–2 mg/m2) on days 2 and 9 and IV paclitaxel at 100 mg/m2 on days 1 and 8 of a 21-day cycle. Dose escalation was based on two end-points: not exceeding 80% 20S-proteasome inhibition (20-S PI) and the development of dose-limiting toxicity defined as grade 3 or greater non-hematologic or grade 4 hematologic toxicities. Forty-five patients with advanced solid tumors and a median of 3 prior chemotherapy regimens (range 0– 9), received 318 doses (median 5, range 1–34) of bortezomib and paclitaxel. Dose-related inhibition of 20-S PI was observed with a maximum inhibition of 70–80% at the MTD of 1.8 mg/m2 of bortezomib. At the MTD (N = 9) the following toxicities were observed: grade 4 neutropenia without fever (n = 2) and cerebrovascular ischemia (n = 1); grade 3 neutropenia (n = 3), diarrhea (n = 2), nausea (n = 1), and fatigue (n = 1); grade 2 fatigue (n = 5), diarrhea (n = 4), and dyspnea (n = 2). There was one partial response in a patient with an eccrine porocarcinoma. Stabilization of disease was observed in 7 (16%) patients, 3 of whom had advanced pancreatic cancer. Sequential paclitaxel and bortezomib in previously treated patients with advanced solid tumors resulted in acceptable toxicity and no evidence of interaction. The recommended phase II dose of bortezomib in combination with weekly paclitaxel was 1.8 mg/m2.
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影响因子：
11.5
作者：
Dreicer, Robert;Petrylak, Daniel;Roth, Bruce
通讯作者：
Roth, Bruce
影响因子：
8.8
作者：
Awada A;Albanell J;Canney PA;Dirix LY;Gil T;Cardoso F;Gascon P;Piccart MJ;Baselga J
通讯作者：
Baselga J
影响因子：
5.7
作者：
Canfield, Steven E.;Zhu, Keyi;McConkey, David J.
通讯作者：
McConkey, David J.
影响因子：
45.3
作者：
Papandreou, CN;Daliani, DD;Logothetis, CJ
通讯作者：
Logothetis, CJ
影响因子：
11.8
作者：
Adams, J
通讯作者：
Adams, J