Bortezomib plus gemcitabine/carboplatin as first-line treatment of advanced non-small cell lung cancer: a phase II Southwest Oncology Group Study (S0339).
Bortezomib plus gemcitabine/carboplatin as first-line treatment of advanced non-small cell lung cancer: a phase II Southwest Oncology Group Study (S0339).
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DOI：
10.1097/jto.0b013e3181915052
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发表时间：
2009-01
期刊：
影响因子：
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通讯作者：
Southwest Oncology Group
中科院分区：
文献类型：
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作者：
Davies AM;Chansky K;Lara PN Jr;Gumerlock PH;Crowley J;Albain KS;Vogel SJ;Gandara DR;Southwest Oncology Group
硼替佐米是一种小分子蛋白酶体抑制剂，在非小细胞肺癌（NSCLC）患者中具有单药活性，在临床前研究中与吉西他滨具有协同作用。这项硼替佐米联合吉西他滨/卡铂的II期研究在未经化疗的晚期NSCLC患者中进行，以评估疗效和安全性。选定的IIIB/IV期NSCLC、体能状态0 - 1、无脑转移病史的患者接受最多6个21天周期的吉西他滨1，000 mg/m2（第1天和第8天）、卡铂AUC 5.0（第1天）和硼替佐米1.0 mg/m2（第1、4、8和11天）治疗。114例患者（52%腺癌，85% IV期）接受了中位3.6个治疗周期。中位随访时间> 3年。中位总生存期（OS）为11个月; 1年和2年生存率分别为47%和19%。中位PFS为5个月; 1年PFS率为7%。缓解率为23%，疾病控制率（缓解+疾病稳定）为68%。最常见的3/4级毒性是血小板减少症（63%）和中性粒细胞减少症（52%）。1例患者发生发热性中性粒细胞减少症。4%的患者发生3/4级神经病变。硼替佐米加吉西他滨/卡铂在晚期NSCLC患者中产生了显著的生存获益，预期主要毒性为骨髓抑制。需要进一步研究硼替佐米在晚期NSCLC中的作用。
Bortezomib is a small-molecule proteasome inhibitor with single-agent activity in patients with non-small cell lung carcinoma (NSCLC) and synergy with gemcitabine in preclinical studies. This phase II study of bortezomib in combination with gemcitabine/carboplatin was conducted in chemotherapy-naïve advanced NSCLC patients to assess efficacy and safety. Patients with selected stage IIIB/IV NSCLC, performance status 0–1, and no history of brain metastasis received up to six 21-day cycles of gemcitabine 1,000 mg/m2, days 1 and 8, carboplatin AUC 5.0, day 1, and bortezomib 1.0 mg/m2, days 1, 4, 8, and 11. 114 patients (52% adenocarcinoma, 85% stage IV) received a median of 3.6 treatment cycles. Median follow-up was > 3 years. Median overall survival (OS) was 11 months; 1-year and 2-year survival rates were 47% and 19%, respectively. Median PFS was 5 months; 1-year PFS rate was 7%. Response rate was 23%, and disease control rate (responses + stable disease) was 68%. The most common grade 3/4 toxicities were thrombocytopenia (63%) and neutropenia (52%). One patient experienced febrile neutropenia. Grade 3/4 neuropathy occurred in 4%. Bortezomib plus gemcitabine/carboplatin resulted in a notable survival benefit in patients with advanced NSCLC, with the anticipated primary toxicity of myelosuppression. Further studies designed to investigate the role of bortezomib in advanced NSCLC are warranted.