Dose escalation of accelerated hypofractionated three-dimensional conformal radiotherapy (at 3 Gy/fraction) with concurrent vinorelbine and carboplatin chemotherapy in unresectable stage III non-small-cell lung cancer: a phase I trial

Radiation Oncology

Jing Hu¹  Zhi-Jun Guo¹  Yu Peng¹  Jie Zong¹  Dong-Ying Wang¹  Xue-Ji Chen¹  Na Wang¹  Xiao-Cang Ren¹  Yue-E Liu¹  Qiang Lin¹ 

[1] Department of Oncology, North China Petroleum Bureau General Hospital of Hebei Medical University, 8 Huizhan Avenue, Renqiu, Hebei Province 062552, P.R. China

关键词: Carboplatin;    Vinorelbine;    Maximum tolerated dose;    Concurrent chemoradiotherapy;    Non-small-cell lung cancer;    Three-dimensional conformal radiotherapy;    Accelerated hypofractionated radiotherapy;   

Others  :  1153217
DOI  :  10.1186/1748-717X-8-201

 received in 2013-03-30, accepted in 2013-08-16,  发布年份 2013

【 摘 要 】

Background

Accelerated hypofractionated radiotherapy can shorten total treatment time and overcome the accelerated repopulation of tumour cells during radiotherapy. This therapeutic approach has demonstrated good efficacy in the treatment of locally advanced non-small-cell lung cancer (NSCLC). However, the optimal fractionation scheme remains uncertain. The purpose of this phase I trial was to explore the maximum tolerated dose (MTD) of accelerated hypofractionated three-dimensional conformal radiotherapy (3-DCRT) (at 3 Gy/fraction) administered in combination with concurrent vinorelbine (NVB) and carboplatin (CBP) chemotherapy for unresectable stage III NSCLC.

Methods

Previously untreated cases of unresectable stage III NSCLC received accelerated hypofractionated 3-DCRT, delivered at 3 Gy per fraction, once daily, with five fractions per week. The starting dose was 66 Gy and an increment of 3 Gy was utilized. Higher doses continued to be tested in patient groups until the emergence of dose-limiting toxicity (DLT). The MTD was regarded as the dose that was one step below the dose at which DLT occurred. Patients received at least one cycle of a concurrent two-drug chemotherapy regimen of NVB and CBP.

Results

A total of 13 patients were enrolled and progressed through three dose escalation groups: 66 Gy, 69 Gy, and 72 Gy. No treatment-related deaths occurred. The major adverse events included radiation oesophagitis, radiation pneumonitis, and neutropenia. Nausea, fatigue, and anorexia were commonly observed, although the magnitude of these events was typically relatively minor. Among the entire group, four instances of DLT were observed, including two cases of grade 3 radiation oesophagitis, one case of grade 3 radiation pneumonitis, and one case of grade 4 neutropenia. All of these cases of DLT occurred in the 72 Gy group. Therefore, 72 Gy was designated as the DLT dose level, and the lower dose of 69 Gy was regarded as the MTD.

Conclusions

For unresectable stage III NSCLC 69 Gy (at 3 Gy/fraction) was the MTD of accelerated hypofractionated 3-DCRT administered in combination with concurrent NVB and CBP chemotherapy. The toxicity of this chemoradiotherapy regimen could be tolerated. A phase II trial is recommended to further evaluate the efficacy and safety of this regimen.

【 授权许可】

   
2013 Lin et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

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