局部晚期不可切除非小细胞肺癌患者行螺旋断层放疗联合同步化疗的 1/2 期剂量递增毒性研究报告。

Toxicity report of a phase 1/2 dose-escalation study in patients with inoperable, locally advanced nonsmall cell lung cancer with helical tomotherapy and concurrent chemotherapy.

机构信息

Department of Radiation Oncology, Oncology Center, Brussels University Hospital, Brussels, Belgium.

出版信息

Cancer. 2010 Jan 1;116(1):241-50. doi: 10.1002/cncr.24732.

DOI:10.1002/cncr.24732

PMID:19918925

Abstract

BACKGROUND

The objective of the current study was to evaluate the feasibility and toxicity of radiation dose escalation with concurrent chemotherapy using helical tomotherapy (HT) in patients with inoperable, locally advanced, stage III nonsmall cell lung cancer (LANSCLC) (grading determined according to the American Joint Committee on Cancer 6th edition grading system).

METHODS

This phase 1/2 study was designed to determine the maximum tolerated dose (MTD) of radiotherapy in patients with LANSCLC administered concurrently with docetaxel and cisplatin. Radiotherapy was delivered using HT. A dose per fraction escalation was applied starting at 2 grays (Gy), with an increase of 6% per dose cohort (DC). The Radiation Therapy Oncology Group acute radiation morbidity score was used to monitor pulmonary, esophageal, and cardiac toxicity.

RESULTS

Dose escalation was performed in 34 patients over 5 DCs to a dose per fraction of 2.48 Gy. No differences were observed in acute toxicity between the different DCs. However, a significant increase in late lung toxicity in DC IV, which received a fraction size of 2.36 Gy, necessitated a halt in further dose escalation with the MTD defined as 2.24 Gy per fraction. The overall incidence of acute grade > or =3 esophageal and pulmonary toxicity was 24% and 3%, respectively (grading determined according to the Radiation Therapy Oncology Group-European Organisation for Research and Treatment of Cancer toxicity scoring system). The overall incidence of late lung toxicity was 21%, but the incidence was an acceptable 13% in DCs I, II, and III. The local response rate was 61% on computed tomography images.

CONCLUSIONS

The use of HT to 67.2 Gy with concurrent cisplatin/docetaxel was feasible and resulted in acceptable toxicity. A full phase 2 study has been initiated to establish the true local response rate at the MTD of 2.24 Gy per fraction.

摘要

背景

本研究旨在评估螺旋断层放疗（HT）同步放化疗治疗不可手术局部晚期 III 期非小细胞肺癌（LANSCLC）（根据美国癌症联合委员会第 6 版分级系统确定分级）患者的可行性和毒性。

方法

该 1/2 期研究旨在确定 LANSCLC 患者同步接受多西他赛和顺铂治疗时的最大耐受剂量（MTD）。采用 HT 进行放射治疗。起始剂量为 2 戈瑞（Gy），每个剂量递增 6%。采用放射治疗肿瘤学组急性放射损伤评分监测肺、食管和心脏毒性。

结果

34 例患者进行了 5 个剂量递增，分次剂量增加到 2.48 Gy。不同剂量递增组之间未观察到急性毒性差异。然而，在第 4 个剂量递增组（2.36 Gy）中，出现了显著的迟发性肺毒性增加，这使得需要停止进一步的剂量递增，将 2.24 Gy 定义为 MTD。急性 > 或 =3 级食管和肺毒性的总发生率分别为 24%和 3%（根据放射治疗肿瘤学组-欧洲癌症研究与治疗组织毒性评分系统进行分级）。迟发性肺毒性的总发生率为 21%，但在第 1、2 和 3 个剂量递增组中发生率为可接受的 13%。在 CT 图像上局部反应率为 61%。