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不可切除的IIIA期和IIIB期非小细胞肺癌患者同步高剂量胸部适形放疗诱导及同期化疗:剂量递增I期试验

Induction and concurrent chemotherapy with high-dose thoracic conformal radiation therapy in unresectable stage IIIA and IIIB non-small-cell lung cancer: a dose-escalation phase I trial.

作者信息

Socinski Mark A, Morris David E, Halle Jan S, Moore Dominic T, Hensing Thomas A, Limentani Steven A, Fraser Robert, Tynan Maureen, Mears Andrea, Rivera M Patricia, Detterbeck Frank C, Rosenman Julian G

机构信息

Multidisciplinary Thoracic Oncology Program, Lineberger Comprehensive Cancer Center, University of North Carolina, CB# 7305, Chapel Hill, NC 27599-7305, USA.

出版信息

J Clin Oncol. 2004 Nov 1;22(21):4341-50. doi: 10.1200/JCO.2004.03.022.

Abstract

PURPOSE

Local control rates at conventional radiotherapy doses (60 to 66 Gy) are poor in stage III non-small-cell lung cancer (NSCLC). Dose escalation using three-dimensional thoracic conformal radiation therapy (TCRT) is one strategy to improve local control and perhaps survival.

PATIENTS AND METHODS

Stage III NSCLC patients with a good performance status (PS) were treated with induction chemotherapy (carboplatin area under the curve [AUC] 5, irinotecan 100 mg/m(2), and paclitaxel 175 mg/m(2) days 1 and 22) followed by concurrent chemotherapy (carboplatin AUC 2 and paclitaxel 45 mg/m(2) weekly for 7 to 8 weeks) beginning on day 43. Pre- and postchemotherapy computed tomography scans defined the initial clinical target volume (CTV(I)) and boost clinical target volume (CTV(B)), respectively. The CTV(I) received 40 to 50 Gy; the CTV(B) received escalating doses of TCRT from 78 Gy to 82, 86, and 90 Gy. The primary objective was to escalate the TCRT dose from 78 to 90 Gy or to the maximum-tolerated dose.

RESULTS

Twenty-nine patients were enrolled (25 assessable patients; median age, 59 years; 62% male; 45% stage IIIA; 38% PS 0; and 38% > or = 5% weight loss). Induction CIP was well tolerated (with filgrastim support) and active (partial response rate, 46.2%; stable disease, 53.8%; and early progression, 0%). The TCRT dose was escalated from 78 to 90 Gy without dose-limiting toxicity. The primary acute toxicity was esophagitis (16%, all grade 3). Late toxicity consisted of grade 2 esophageal stricture (n = 3), bronchial stenosis (n = 2), and fatal hemoptysis (n = 2). The overall response rate was 60%, with a median survival time and 1-year survival probability of 24 months and 0.73 (95% CI, 0.55 to 0.89), respectively. CONCLUSION Escalation of the TCRT dose from 78 to 90 Gy in the context of induction and concurrent chemotherapy was accomplished safely in stage III NSCLC patients.

摘要

目的

Ⅲ期非小细胞肺癌(NSCLC)采用传统放疗剂量(60至66 Gy)时局部控制率较低。使用三维胸部适形放疗(TCRT)增加剂量是提高局部控制率并可能改善生存率的一种策略。

患者与方法

对体能状态(PS)良好的Ⅲ期NSCLC患者先进行诱导化疗(卡铂曲线下面积[AUC] 5、伊立替康100 mg/m²、紫杉醇175 mg/m²,第1天和第22天),然后从第43天开始进行同步化疗(卡铂AUC 2、紫杉醇45 mg/m²,每周1次,共7至8周)。化疗前和化疗后的计算机断层扫描分别确定初始临床靶体积(CTV(I))和推量临床靶体积(CTV(B))。CTV(I)接受40至50 Gy照射;CTV(B)接受递增剂量的TCRT照射,剂量从78 Gy递增至82、86和90 Gy。主要目的是将TCRT剂量从78 Gy递增至90 Gy或至最大耐受剂量。

结果

入组29例患者(25例可评估患者;中位年龄59岁;62%为男性;45%为ⅢA期;38% PS为0;38%体重减轻≥5%)。诱导化疗(CIP)耐受性良好(有非格司亭支持)且疗效显著(部分缓解率46.2%;疾病稳定率53.8%;早期进展率0%)。TCRT剂量从78 Gy递增至90 Gy,未出现剂量限制性毒性。主要急性毒性为食管炎(16%,均为3级)。晚期毒性包括2级食管狭窄(n = 3)、支气管狭窄(n = 2)和致命咯血(n = 2)。总缓解率为60%,中位生存时间和1年生存概率分别为24个月和0.73(95% CI,0.55至0.89)。结论:在诱导化疗和同步化疗的背景下,Ⅲ期NSCLC患者的TCRT剂量从78 Gy安全递增至90 Gy。

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