Erlotinib plus bevacizumab in previously treated patients with malignant pleural mesothelioma
Erlotinib plus bevacizumab in previously treated patients with malignant pleural mesothelioma
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DOI：
10.1002/cncr.23617
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发表时间：
2008-08-15
期刊：
影响因子：
6.2
通讯作者：
Janne, Pasi A.
中科院分区：
文献类型：
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作者：
Jackman, David M.;Kindler, Hedy L.;Janne, Pasi A.
背景。我们对曾接受过1次化疗方案的恶性胸膜间皮瘤患者进行了厄洛替尼联合贝伐单抗的2期、多中心、开放标签研究。这些药物在非小细胞肺癌中有活性，但在间皮瘤中的作用尚不清楚。主要终点是有效率。次要终点包括进展时间、生存期和毒性。先前接受过1次化疗方案的间皮瘤患者在21天周期的第1天静脉给予厄洛替尼150mg / s / d和贝伐单抗15rng /kg。治疗持续至疾病进展或出现显著毒性。采用Byrne和nowak先前建立的间皮瘤反应标准，每2个周期后评估肿瘤反应。2004年2月至2006年10月，24名符合条件的患者开始接受厄洛替尼和贝伐单抗治疗。没有完全或部分缓解，尽管12例患者在至少2个治疗周期内病情稳定。中位进展时间为2.2个月（95%可信区间[CI]， 1.4 -5.9个月）。中位生存期为5.8个月（95% Cl， 2.8个月-10.1个月）。最常见的毒性是皮疹和腹泻。无治疗相关死亡、颅内出血或咯血。厄洛替尼和贝伐单抗的联合耐受性相当好，但没有证据表明放射学反应。本研究证明了在一线治疗失败的间皮瘤患者中进行试验的可行性，需要对这些患者进行更多有效药物的治疗研究。
BACKGROUND. We conducted a phase 2, multicenter, open-label study of erlotinib plus bevacizumab in patients with malignant pleural mesothelioma who had previously received 1 prior chemotherapy regimen. These agents have activity in non-small cell lung cancer, but their role in mesothelioma is unclear. The primary endpoint is response rate. Secondary endpoints include time to progression, survival, and toxicityMETHODS. Eligible patients with mesothelioma who had previously received 1 chemotherapy regimen were treated with erlotinib 150 mg per os daily and bevacizumab 15 rng/kg administered intravenously on Day 1 of a 21-day cycle. Treatment continued until disease progression or development of significant toxicity. Tumor response was assessed after every 2 cycles using previously established mesothelioma response criteria from Byrne and Nowak.RESULTS. Twenty-four eligible patients initiated therapy with erlotinib and bevacizumab between February 2004 and October 2006. There were no complete or partial responses, although 12 patients achieved stable disease for at least 2 cycles of treatment. The median time to progression was 2.2 months (95% confidence interval [CI], 1.4 months-5.9 months). The median survival was 5.8 months (95% Cl, 2.8 nionths-10.1 months). The most common toxicities were rash and diarrhea. There were no treatment- related deaths, intracranial bleeding, or hemoptysis.CONCLUSIONS. The combination of erlotinib and bevacizumab was tolerated reasonably well, but there was no evidence of radiographic response. This study demonstrates the feasibility of conducting trials in mesothelioma patients who have failed first-line therapy More therapeutic studies with effective agents are needed for these patients.