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Strahlentherapie und Onkologie

, Volume 192, Issue 4, pp 216–222 | Cite as

GILT—A randomised phase III study of oral vinorelbine and cisplatin with concomitant radiotherapy followed by either consolidation therapy with oral vinorelbine and cisplatin or best supportive care alone in stage III non-small cell lung cancer

  • Michael Flentje
  • Rudolf M. Huber
  • Walburga Engel-Riedel
  • Stefan Andreas
  • Jens Kollmeier
  • Susanne Staar
  • Nicolas Dickgreber
  • Nathalie Vaissiere
  • Cecilia De Almeida
  • Birgit Edlich
  • Rainer Fietkau
Original Article

Abstract

Background

Concurrent chemoradiotherapy (CRT) is considered standard for inoperable stage III non-small cell lung cancer (NSCLC). Consolidation chemotherapy (CC) following CRT is intended to further improve outcomes, yet studies have shown discordant results. This phase III study assessed CRT followed by best supportive care (BSC) or consolidation with oral vinorelbine and cisplatin.

Methods

Patients received two cycles of oral vinorelbine (50 mg/m2 days 1, 8 and 15) + cisplatin (20 mg/m2 days 1–4) q4w + radiotherapy (RT; 66 Gy). Patients with at least stable disease (SD) were randomised to either two cycles oral vinorelbine (60–80 mg/m2 days 1 and 8) + cisplatin (80 mg/m2 day 1) q3w + BSC or BSC alone. Primary endpoint was progression-free survival (PFS).

Results

A total of 279 patients were enrolled for CRT and 201 patients were randomised to CC or BSC. Both CRT and CC were well tolerated, with limited radiation-mediated grade 3/4 toxicities (CRT/CC/BSC: oesophagitis-related events 12.9 %/3.1 %/0 %; grade 3 pneumonitis 0 %/0 %/2 %) and chemotherapy-mediated grade 3/4 toxicities (CRT/CC: neutropenia 11.2 %/22.1 %; leukopenia 18.3 %/26.7 %; grade 3 nausea 5.0 %/2.3 %, grade 3 vomiting 3.2 %/3.5 %). Median PFS from randomisation was 6.4 (5.0–8.7) and 5.5 (3.8–7.4) months in the CC and BSC arms (hazard ratio, HR = 0.93 [0.69–1.26]; p = 0.63), respectively; median overall survival (OS) 20.8 (13.5–25.3) and 18.5 (13.6–24.7) months, respectively.

Discussion

Consolidation chemotherapy after concurrent CRT did not prolong PFS or OS. Concurrent RT with oral vinorelbine and cisplatin demonstrated a favourable safety profile and represents a suitable treatment regimen for inoperable stage III NSCLC.

Keywords

Chemoradiotherapy Survival Toxicity Combined modality therapy Consolidation chemotherapy 

GILT – Eine randomisierte Phase-III-Studie mit oralem Vinorelbin und Cisplatin plus konkomitanter Strahlentherapie gefolgt von konsolidierender Therapie mit oralem Vinorelbin und Cisplatin oder bestmöglicher supportiver Therapie bei nicht-kleinzelligem Lungenkarzinom Stadium III

Zusammenfassung

Hintergrund

Simultane Radiochemotherapie (CRT) wird als Standardtherapie beim inoperablen Stadium III des nicht-kleinzelligen Lungenkarzinoms (NSCLC) angesehen. Konsolidierende Chemotherapie (CC) nach der CRT zielt darauf ab, das Therapieergebnis zu verbessern, allerdings zeigen Studien widersprüchliche Ergebnisse. In dieser Phase-III-Studie wurde CRT mit anschließender "best supportive care" (BSC) oder Konsolidierung mit oralem Vinorelbin und Cisplatin bewertet.

Methoden

Die Patienten wurden mit 2 Zyklen oralem Vinorelbin (50 mg/m2, Tag 1, 8 und 15) + Cisplatin (20 mg/m2, Tag 1–4) q4w + Radiotherapie (RT, 66 Gy) behandelt. Patienten, die mindestens eine Krankheitskontrolle aufwiesen, wurden zu 2 Zyklen oralem Vinorelbin (60–80 mg/m2, Tag 1 und 8) + Cisplatin (80 mg/m2, Tag 1) q3w mit BSC oder alleiniger BSC randomisiert. Primärer Endpunkt war das progressionsfreie Überleben (PFS).

Ergebnisse

Für die CRT wurden 279 Patienten eingeschlossen und 201 Patienten für CC oder BSC randomisiert. CRT und CC wurden jeweils gut vertragen und wiesen wenige Fälle von strahlenbedingten Grad-3/4-Toxizitäten (CRT/CC/BSC: ösophagitisassoziierte Ereignisse 12,9 %/3,1 %/0 %, G3-Pneumonitis 0 %/0 %/2 %) und chemotherapiebedingte Grad-3/4-Toxizitäten [CRT/CC: Neutropenie 11,2 %/22,1 %, Leukopenie 18,3 %/26,7 %; Übelkeit 5,0 %/2,3 % (G3), Erbrechen 3,2 %/3,5 % (G3)] auf. Im CC- und BSC-Arm betrug das mediane PFS vom Zeitpunkt der Randomisierung jeweils 6,4 (5,0–8,7) bzw. 5,5 (3,8–7,4) Monate [Hazard Ratio (HR) 0,93 (0,69–1,26); p = 0,63] und das mediane Überleben (OS) 20,8 (13,5–25,3) bzw. 18,5 (13,6–24,7) Monate.

Diskussion

CC nach simultaner CRT führte nicht zu einer Verlängerung des PFS oder OS. Simultane RT mit oralem Vinorelbin und Cisplatin wies ein vorteilhaftes Sicherheitsprofil auf und stellt damit ein geeignetes Behandlungsregime für NSCLC-Patienten mit inoperablem Stadium III dar.

Schlüsselwörter

Chemoradiotherapie Überleben Toxizität Kombinierte modale Therapie Konsolidierungschemotherapie 

Notes

Acknowledgements

We thank all participating centers: M. Allgaeuer, Krankenhaus der Barmherzigen Brueder Regensburg; S. Baesecke, SRH Zentralklinikum Suhl; G. Becker, Klinikum am Eichert Goeppingen; M. Bieker, Universitaetsklinikum Marburg; R. Bonnet, Zentralklinikum Bad Berka; M. Degen, Pneumologische Klinik Greifenstein; N. Dickgreber, Medizinische Hochschule Hannover, W. Dornoff, Mutterhaus der Borromaeerinnen Trier; P. Feyer, Vivantes Klinikum Neukoelln; L. Fischer von Weikersthal, Klinikum St. Marien Amberg; F. Griesinger, Pius Hospital Oldenburg; S. Guetz/A. Friedrichs, Klinikum St. Georg Leipzig; F. Heinemann, Krankenhaus Donaustauf; G. Hildebrandt, Universitaetsklinikum Rostock; G. Hildebrandt, Klinik und Poliklinik für Radiotherapie und Radioonkologie Leipzig; W. Hinkelbein, Charité Campus Benjamin Franklin Berlin; W. Hoffmann, Staedtisches Klinikum Braunschweig; A. Jakob, Klinikum Offenburg; C. Jung, Gemeinschaftspraxis Jung/Kronawitter Traunstein; M. van Kampen, Krankenhaus Nordwest Frankfurt; H. Kirchen, Krankenhaus der Barmherzigen Brueder Trier; B. Kober, Klinikum Darmstadt; O. Koelbl, Universitätsklinikum Regensburg; W. Koerber, Evangelisches Krankenhaus Bovenden-Lenglern; J. Mezger, St.-Vincentius Klinik Karlsruhe; P. Mueller, Universitaetsklinik Koeln; N. Niederle, Klinikum Leverkusen; K. Pfaendner, Leopoldina Krankenhaus Schweinfurt; C. Ruebe, Universitaetsklinik des Saarlandes Homburg; B. Schilcher, Helios Klinikum Wuppertal; C. Schumann, Universitaetsklinikum Ulm; S. Schuettrumpf, Universitaetsklinikum Goettingen; M. Serke, Lungenklinik Hemer; U. Sibelius, Universitaetsklinikum Giessen; H. Simon, Paracelsus Klinik Ruit; E. Standke, Heinrich-Braun-Krankenhaus Zwickau; C. Steppert, Bezirksklinikum; T. G. Wendt, Universitaetsklinikum Jena; F. Wenz, Klinikum Mannheim; T. Wiegel, Universitaetsklinikum Ulm; J. Willner, Klinikum Bayreuth; N. Zamboglou, Klinikum Offenbach; K. Ziegler, Klinikum Ansbach and all the patients and their relatives. Medical writing services for finalisation were provided by R. Howell, Aerian Consulting Wellesley USA.

Source of Funding

The study was funded by the Institut de Recherche Pierre Fabre, France.

Compliance with ethical guidelines

Conflicts of interest

JK reports grants to his institution by Pierre Fabre; SA reports financial support by Roche, GlaxoSmithKline, Boehringer Ingelheim and Eli Lilly; RH reports funding by Pierre Fabre; RF reports financial support by Pierre Fabre, Roche and Eli Lilly; MF reports funding by Pierre Fabre. NV, CDA and BE are employees of Pierre Fabre. WER, SS and ND state that there are no conflicts of interest.

All studies on humans described in the present manuscript were carried out with the approval of the responsible ethics committee and in accordance with national law and the Helsinki Declaration of 1975 (in its current, revised form). Informed consent was obtained from all patients included in studies.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • Michael Flentje
    • 1
  • Rudolf M. Huber
    • 2
  • Walburga Engel-Riedel
    • 3
  • Stefan Andreas
    • 4
  • Jens Kollmeier
    • 5
  • Susanne Staar
    • 6
  • Nicolas Dickgreber
    • 7
  • Nathalie Vaissiere
    • 8
  • Cecilia De Almeida
    • 8
  • Birgit Edlich
    • 9
  • Rainer Fietkau
    • 10
  1. 1.Dept. of RadiotherapyUniversity hospital WuerzburgWuerzburgGermany
  2. 2.Member of the German Center for Lung Research (DZL CPC-M)University hospital MunichMunichGermany
  3. 3.University Hospital Merheim, Dept.of PneumonologyCologneGermany
  4. 4.Dept.of PneumonologyImmenhausenGermany
  5. 5.Helios Emil-von-Behring HospitalBerlinGermany
  6. 6.Municipal Hospital Bremen-MitteBremenGermany
  7. 7.University hospital HannoverHannoverGermany
  8. 8.Institut de Recherche Pierre FabreBoulogneFrance
  9. 9.Pierre Fabre Pharma GmbHFreiburgGermany
  10. 10.University Hospital ErlangenErlangenGermany

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