How to improve loco-regional control in stages IIIa–b NSCLC?: Results of a three-armed randomized trial from the Swedish Lung Cancer Study Group
Introduction
Induction chemotherapy and radiotherapy has been the treatment base for locally advanced non-small cell lung cancer (NSCLC). However, both loco-regional and distant failure is frequent. Attempts to improve the loco-regional control were made in three separate phase II studies in different Swedish University Hospitals. Accelerated fractionated radiotherapy combined with induction and concomitant chemotherapy was used in one study [1], [2]. Induction chemotherapy followed by concomitant daily paclitaxel with conventional fractionated radiotherapy followed by adjuvant chemotherapy was explored in a phases I–II setting in a second study [3]. The third study investigated induction chemotherapy followed by weekly paclitaxel and carboplatin combined with conventional fractionated radiotherapy [4]. Comparatively good results from these studies lead to this national randomized phase II study, the RAKET-study, where the different concepts were investigated on a wider basis with time to progression as primary endpoint for a further phase III study. An interim analysis was planned where one arm could be stopped if it did not meet the efficacy rate of clinical interest (TTP > 12 months) and a conversion to a two armed randomized phase III study would then be possible. A second goal was to achieve a national unity in the treatment strategies for this patient group.
Section snippets
Objectives
One hundred and fifty patients were planned for this study equally randomized to three treatment arms where the primary objective was time to progression (TTP) and secondary objectives were response, overall survival, toxicity, quality of life (QLQ) and relapse pattern. Additionally, possible prognostic and predictive factors should be looked for.
Patient eligibility
The main inclusion criteria were non-resectable or medically inoperable patients with histological or cytological confirmed NSCLC stage IIIa or IIIb
Patient characteristics
Between June 2002 and May 2005 152 patients were randomized and 151 of them were evaluable, one patient had stage IV disease at inclusion and was excluded. There were 78 men and 73 women, median age was 62 years (range 43–78), 55% had performance status 0 and 45% PS 1. Mean pretreatment pulmonary function: FEV1 2.1 L (range 0.8–4.5). Pretreatment weight loss >10% was seen in 20 patients (13%). Thirty-four percent had stage IIIa and 66% IIIb. Adenocarcinoma was the most common histology in 48%,
Discussion
Both local and distant relapse is frequent in locally advanced stage III NSCLC.
To reduce the distant failure we used induction chemotherapy in all arms in this study. There are some data supporting that full dose induction chemotherapy reduces distant metastases whereas concomitant chemotherapy could improve the local control [6]. However, two recent studies did not show any additional value of induction chemotherapy when using concomitant chemoradiation [7], [8]. In earlier studies in Japan
Conflict of interest
The authors indicate no potential conflict of interest.
Acknowledgements
We would like to thank Ingmarie Johanson for help with to statistics, Camilla Palmqvist for monitoring the study and Bristol-Myers Squibb Scandinavia for an unrestricted grant to be able to accomplish the study.
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Swedish Lung Cancer Study Group.