阿帕替尼治療多線化療后復發的廣泛期小細胞肺癌的效果及對患者生存的影響

張海利 董桂蘭 劉麗麗 谷雪 呂立麗 胡萬寧 王志武

[摘要] 目的 觀察阿帕替尼治療既往接受過多線化療進展的廣泛期小細胞肺癌（SCLC）患者的近期療效、安全性及其對患者生存的影響。 方法 回顧性納入2017年1月～2018年6月于唐山市人民醫院放化療科接受阿帕替尼治療的SCLC患者62例。用藥1個周期（4周）后首次評價療效，之后每2個周期行一次療效評價。主要研究終點為無進展生存期（PFS），次要終點為總生存期（OS），采用Kaplan-Meier曲線評估PFS，應用Log-rank對比組間生存差異，根據RECIST 1.1標準評估療效，根據CTCAE 4.0標準評估不良反應。 結果 62例SCLC患者中無CR病例，11例（17.7%）達PR，37例（59.7%）為SD，PD為14例（22.6%）。DCR為48例（77.4%）。中位PFS為3個月（95%CI：1.13～4.87），中位OS為6個月（95%CI：4.27～7.73）。最常見不良反應為繼發性高血壓（28/62）和手足綜合征（34/62），3級不良反應共發生3例。 結論 阿帕替尼在廣泛期SCLC三線或四線治療中有確切效果，不良反應可耐受。該結果尚需在多中心、大樣本量的前瞻性研究中驗證。

[關鍵詞] 阿帕替尼;小細胞肺癌;生存分析;不良反應

[中圖分類號] R734.2? ? ? ? ? [文獻標識碼] A? ? ? ? ? [文章編號] 1673-7210（2019）09（b）-0100-04

Effect of Apatinib in the treatment of recurrent extensive small cell lung cancer after multi-line chemotherapy and its impact on the survival of patients

ZHANG Haili? ?DONG Guilan? ?LIU Lili? ?GU Xue? ?LYU Lili? ?HU Wanning? ?WANG Zhiwu▲

Department of Radiotherapy and Chemotherapy， Tangshan People′s Hospital， Hebei Province， Tangshan? 063000， China

[Abstract] Objective To observe the short-term efficacy， safety and survival of Apatinib in the treatment of patients with extensive small cell lung cancer （SCLC） who had previously undergone multiline chemotherapy. Methods A retrospective study of 62 SCLC patients treated with Apatinib in Department of Radiotherapy and Chemotherapy， Tangshan People′s Hospital from January 2017 to June 2018. The efficacy was evaluated for the first time after 1 cycle （4 weeks）. Thereafter， the efficacy was evaluated every two cycles. The primary endpoint was progression-free survival （PFS） and the secondary endpoint was total survival （OS）. Kaplan-Meier curve was used to evaluate PFS. Log-rank was used to compare survival differences between groups. The efficacy was evaluated according to RECIST 1.1 criteria， and adverse reactions were evaluated according to CTCAE 4.0 criteria. Results Among the 62 patients with SCLC， there were no CR cases， 11 cases （17.7%） with PR， 37 cases （59.7%） with SD and 14 cases （22.6%） with PD. DCR was 48 cases （77.4%）. The median PFS was 3 months （95%CI： 1.13-4.87） and the median OS was 6 months （95%CI： 4.27-7.73）. The most common adverse reactions were secondary hypertension （28/62） and hand-foot syndrome （34/62）， and grade 3 adverse reactions occurred in 3 cases. Conclusion Apatinib has a definite effect in the third or fourth line treatment of extensive SCLC， and the adverse reactions are tolerable. The results need to be validated in a multi-center， large-sample prospective study.

本研究的主要缺陷是回顧性研究，存在產生偏倚結果的風險，且樣本量較小，不足以進行多因素分析，不能進一步探討影響阿帕替尼治療敏感性的相關因素。因此我們期待目前正在進行中的前瞻性研究的最終結果，同時也計劃開展自己的前瞻性研究來進一步觀察阿帕替尼的療效。本研究是目前報道的關于阿帕替尼用于SCLC治療的研究中樣本量最大的研究。研究發現阿帕替尼作為三線或四線治療，在廣泛期SCLC中療效確切，不良反應可耐受。該結果尚需在多中心、大樣本量的前瞻性研究中驗證。

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（收稿日期：2019-02-13? 本文編輯：李亞聰）