Clinical Research Papers:
A phase II openlabel multicenter study of gefitinib in combination with irradiation followed by chemotherapy in patients with inoperable stage III nonsmall cell lung cancer
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Antonin Levy1,2,3, Etienne Bardet4, Benjamin Lacas5,6, Jean-Pierre Pignon5,6, Julien Adam7, Ludovic Lacroix7, Xavier Artignan8,10, Pierre Verrelle9 and Cécile Le Péchoux1
1 Department of Radiation Oncology, Gustave Roussy, Université Paris-Saclay, Institut Thoracique d’Oncologie (IOT), Villejuif, France
2 INSERM U1030, Molecular Radiotherapy, Gustave Roussy, Université Paris-Saclay, Villejuif, France
3 Univ Paris Sud, Université Paris-Saclay, Le Kremlin-Bicêtre, France
4 Department of Medical Oncology, Institut de Cancérologie de l’Ouest, Nantes, France
5 Gustave Roussy, Université Paris-Saclay, Department of Biostatistics and Epidemiology, Villejuif, France
6 INSERM U1018, CESP, Université Paris-Sud, Université Paris-Saclay, Villejuif, France
7 Department of Medical Biology and Pathology, Translational Research Laboratory and Biobank (UMS3655 CNRS / US23 INSERM), INSERM Unit U981, Villejuif, France
8 Department of Radiation Oncology, University Hospital Grenoble, Grenoble, France
9 Department of Radiation Oncology, Centre Jean Perrin, Clermont-Ferrand, France
10 Department of Radiation Oncology, St Grégoire Hospital, St Grégoire, France
Correspondence to:
Cécile Le Péchoux, email:
Keywords: iressa, thoracic radiotherapy, lung cancer, phase II trial
Received: July 06, 2016 Accepted: October 12, 2016 Published: October 18, 2016
Abstract
Background: Gefitinib is an oral EGFR tyrosine kinase inhibitors which may act as a radiosensitizer.
Patients and Methods: This phase II study evaluated the efficacy of gefitinib 250 mg once daily in combination with thoracic radiotherapy (66 Gy in 6.5 weeks, 2 Gy/day, 5 fractions/week) followed by consolidation chemotherapy (IV cisplatin and vinorelbine) as first line treatment in a population of unselected stage IIIB NSCLC patients according to EGFR mutation status.
Results: Due to a low accrual rate in this study, the sample size (n = 50) was not reached. Sixteen patients were included in four centers, 50% had adenocarcinoma and 75% were male. Genomic alterations (7 patients studied) retrieved TP53 mutation in 2 patients and no EGFR mutation. Four weeks after radiotherapy, 3 patients (19%) had a partial response, 6 (38%) had a stable disease, and 7 had a progression (44%). Median overall survival was 11 months and median progression-free survival was 5 months. At the time of the last contact, 5 patients (31%) were still alive. Main toxicities were gastrointestinal (81%), cutaneous (81%), general (56%), and respiratory (50%). There were 12>G3 adverse events in 7 (47%) patients, and there was one toxic-death during the concomitant period due to an interstitial pneumonitis. There were two possible adverse events-related deaths during the chemotherapy period (pulmonary embolism (n = 1) and sudden death after the administration of the 3rd course of chemotherapy (n = 1)).
Conclusion: The benefit of Gefitinib-RT could not be confirmed due to premature trial discontinuation. Further evaluation is required, especially in patients with EGFR mutated NSCLC.