A study of paclitaxel, carboplatin, and bortezomib in the treatment of metastatic malignant melanoma: a phase 2 consortium study.
A study of paclitaxel, carboplatin, and bortezomib in the treatment of metastatic malignant melanoma: a phase 2 consortium study.
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DOI：
10.1002/cncr.25191
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发表时间：
2010-07-15
期刊：
影响因子：
6.2
通讯作者：
Erlichman, Charles
中科院分区：
文献类型：
--
作者：
Croghan, Gary A.;Suman, Vera J.;Maples, William J.;Albertini, Mark;Linette, Gerald;Flaherty, Lawrence;Eckardt, John;Ma, Cynthia;Markovic, Svetomir N.;Erlichman, Charles
化疗对转移性黑色素瘤患者的生存率没有显著影响。硼替佐米显示出与包括紫杉醇和铂在内的许多化疗剂具有相加/协同效应。这种3种药物联合治疗的I期试验报告，28名接受硼替佐米治疗的患者中有6名接受紫杉醇和卡铂治疗，部分缓解（包括5名转移性黑色素瘤患者中的2名）。我们进行了一项2阶段II期临床试验，以评估这种3种药物组合在转移性黑色素瘤患者中的抗肿瘤活性，这些患者既往最多接受过一次转移性疾病化疗。治疗包括硼替佐米1.3 mg/m2 IV（第1、4和8天），紫杉醇175 mg/m2和卡铂AUC 6（第2天），21天为一个周期。本试验的主要终点为肿瘤缓解率。入组了17例合格患者。给予中位4个周期（范围1-7）。3例患者因持续性4级中性粒细胞减少伴3级白细胞减少（2例患者）或4级肺栓塞（1例患者）而停止治疗。≥ 3级毒性包括中性粒细胞减少（71%）、白细胞减少（41%）、血小板减少（29%）和关节痛（12%）。观察到2例部分缓解（TRR 11.8%）。4例患者病情稳定> 12周。中位无进展生存期（PFS）为3.2个月，中位生存期为7.0个月。由于临床疗效不足，本试验未进入第二阶段招募。紫杉醇、卡铂和硼替佐米的联合治疗显示出有限的临床获益，并伴有显著的毒性。
Chemotherapy has not had significant impact on survival for patients with metastatic melanoma. Bortezomib was shown to have additive/synergistic effect with a number of chemotherapeutic agents including paclitaxel and platinum. A phase I trial of this 3-drug combination reported that 6 of 28 patients treated with bortezomib followed by paclitaxel and carboplatin had a partial response (including 2 of 5 patients with metastatic melanoma). We conducted a 2-stage phase II clinical trial to assess the anti-tumor activity of this 3-agent combination in patients with metastatic melanoma who had received at most one prior chemotherapy for metastatic disease. Treatment included bortezomib 1.3 mg/m2 IV on days 1, 4, and 8, and paclitaxel 175 mg/m2 and carboplatin AUC 6 on day 2 of a 21 day cycle. The primary endpoint of this trial was tumor response rate. Seventeen eligible patients were enrolled. A median of 4 cycles were administered (range 1-7). Three patients discontinued treatment due to persistent grade 4 neutropenia with grade 3 leukopenia (two patients) or grade 4 pulmonary embolism (one patient). Grade ≥ 3 toxicities included neutropenia (71%), leukopenia (41%), thrombocytopenia (29%), and arthralgia (12%). Two partial responses were observed (TRR 11.8%). Four patients had stable disease > 12 weeks. Median progression free survival (PFS) was 3.2 months and median survival 7.0 months. Due to insufficient clinical efficacy, this trial did not proceed to second stage accrual. The combination of paclitaxel, carboplatin, and bortezomib demonstrated limited clinical benefit and was associated with significant toxicity.
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影响因子：
45.3
作者：
Chapman, PB;Einhorn, LH;Kirkwood, JM
通讯作者：
Kirkwood, JM
影响因子：
45.3
作者：
Avril, MF;Aamdal, S;Menu, Y
通讯作者：
Menu, Y
影响因子：
6.2
作者：
Markovic, SN;Geyer, SM;Erlichman, C
通讯作者：
Erlichman, C
影响因子：
3
作者：
Ma, Cynthia;Mandrekar, Sumithra J.;Adjei, Alex A.
通讯作者：
Adjei, Alex A.
影响因子：
45.3
作者：
Middleton, MR;Grob, JJ;Thatcher, N
通讯作者：
Thatcher, N