Advertisement

Clinical and Translational Oncology

, Volume 20, Issue 11, pp 1467–1473 | Cite as

Concurrent chemoradiation for locally advanced stage III non-small cell lung cancer with cisplatin, vinorelbine, and thoracic radiotherapy: a phase II study from the Galician Lung Cancer Group

  • M. Costa Rivas
  • G. Huidobro Vence
  • J. L. Fírvida Pérez
  • B. Campos Balea
  • J. García Gonzalez
  • M. Lázaro Quintela
  • M. Caeiro Muñoz
  • B. Taboada Valladares
  • J. E. Castro Gómez
  • S. Vázquez Estevez
  • F. J. Afonso Afonso
  • C. Azpitarte Raposeiras
  • M. Amenedo Gancedo
  • J. Casal Rubio
Research Article

Abstract

Purpose

The aim of this phase II study was to evaluate the activity and safety of the combination of cisplatin and vinorelbine with thoracic radiotherapy in unresectable locally advanced stage III non-small cell lung cancer (NSCLC). The primary endpoint was the objective response rate (ORR). Secondary objectives included toxicity profile, progression-free survival (PFS), and overall survival (OS).

Materials and methods

A total of 48 NSCLC patients were enrolled (median age 60 years, 52% stage IIIA and 48% stage IIIB, 52% adenocarcinoma). Patients received three cycles of chemotherapy every 21 days [intravenous cisplatin 80 mg/m2 and intravenous vinorelbine 25 mg/m2 on day 1 and oral vinorelbine on day 8 (60 mg/m2)] concurrent with radiotherapy (66 Gy, administered at 1.8 Gy per day, five consecutive days per week).

Results

ORR was 79.2% (72.9% showing partial response and 6.3% showing complete response). With a median follow-up of 20.7 months, median PFS was 12 months and median OS was 36 months. Grade 3/4 toxicities were: neutropenia (14.5%), anaemia (6.2%), vomiting (2%), and oesophagitis (4.2%). No toxic deaths were reported.

Conclusion

This combined regimen shows efficacy and a manageable safety profile. PFS and OS outcomes are encouraging and warrant further research.

Keywords

Non-small cell lung cancer Cisplatin Vinorelbine Thoracic radiotherapy 

Notes

Acknowledgements

Medical writing support was provided by Dr. Almudena Fuster-Matanzo of Medical Statistics Consulting S.L. (Valencia).

Compliance with ethical standards

Conflict of interest

The authors had no conflict of interest in this study.

Ethical approval

The protocol of this trial was approved by the ethics committee of each participating hospital and met the ethical principles stated in the Declaration of Helsinki.

Informed consent

Informed consent was obtained from all individual participants included in the study.

References

  1. 1.
    Postmus PE, Kerr KM, Oudkerk M, Senan S, Waller DA, Vansteenkiste J, et al. Early and locally advanced non-small-cell lung cancer (NSCLC): ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2017;28(suppl_4):1–21.  https://doi.org/10.1093/annonc/mdx222.CrossRefGoogle Scholar
  2. 2.
    Siegel RL, Miller KD, Jemal A. Cancer statistics, 2018. CA Cancer J Clin. 2018;68(1):7–30.  https://doi.org/10.3322/caac.21442.CrossRefGoogle Scholar
  3. 3.
    Tabchi S, Kassouf E, Rassy EE, Kourie HR, Martin J, Campeau MP, et al. Management of stage III non-small cell lung cancer. Semin Oncol. 2017;44(3):163–77.  https://doi.org/10.1053/j.seminoncol.2017.10.009.CrossRefPubMedGoogle Scholar
  4. 4.
    Auperin A, Le Pechoux C, Pignon JP, Koning C, Jeremic B, Clamon G, et al. Concomitant radio-chemotherapy based on platin compounds in patients with locally advanced non-small cell lung cancer (NSCLC): a meta-analysis of individual data from 1764 patients. Ann Oncol. 2006;17(3):473–83.  https://doi.org/10.1093/annonc/mdj117.CrossRefPubMedGoogle Scholar
  5. 5.
    Auperin A, Le Pechoux C, Rolland E, Curran WJ, Furuse K, Fournel P, et al. Meta-analysis of concomitant versus sequential radiochemotherapy in locally advanced non-small-cell lung cancer. J Clin Oncol. 2010;28(13):2181–90.  https://doi.org/10.1200/jco.2009.26.2543.CrossRefPubMedGoogle Scholar
  6. 6.
    Curran WJ Jr, Paulus R, Langer CJ, Komaki R, Lee JS, Hauser S, et al. Sequential vs. concurrent chemoradiation for stage III non-small cell lung cancer: randomized phase III trial RTOG 9410. J Natl Cancer Inst. 2011;103(19):1452–60.  https://doi.org/10.1093/jnci/djr325.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Furuse K, Fukuoka M, Kawahara M, Nishikawa H, Takada Y, Kudoh S, et al. Phase III study of concurrent versus sequential thoracic radiotherapy in combination with mitomycin, vindesine, and cisplatin in unresectable stage III non-small-cell lung cancer. J Clin Oncol. 1999;17(9):2692–9.  https://doi.org/10.1200/jco.1999.17.9.2692.CrossRefPubMedGoogle Scholar
  8. 8.
    Steuer CE, Behera M, Ernani V, Higgins KA, Saba NF, Shin DM, et al. Comparison of concurrent use of thoracic radiation with either carboplatin-paclitaxel or cisplatin-etoposide for patients with stage III non-small-cell lung cancer: a systematic review. JAMA Oncol. 2017;3(8):1120–9.  https://doi.org/10.1001/jamaoncol.2016.4280.CrossRefPubMedGoogle Scholar
  9. 9.
    Zatloukal P, Petruzelka L, Zemanova M, Havel L, Janku F, Judas L, et al. Concurrent versus sequential chemoradiotherapy with cisplatin and vinorelbine in locally advanced non-small cell lung cancer: a randomized study. Lung Cancer (Amsterdam, Netherlands). 2004;46(1):87–98.  https://doi.org/10.1016/j.lungcan.2004.03.004.CrossRefGoogle Scholar
  10. 10.
    O’Rourke N, Roque IFM, Farre Bernado N, Macbeth F. Concurrent chemoradiotherapy in non-small cell lung cancer. Cochrane Database Syst Rev. 2010;6:140.  https://doi.org/10.1002/14651858.cd002140.pub3.CrossRefGoogle Scholar
  11. 11.
    Lena MD, Ramlau R, Hansen O, Lorusso V, Wagner L, Barni S, et al. Phase II trial of oral vinorelbine in combination with cisplatin followed by consolidation therapy with oral vinorelbine in advanced NSCLC. Lung Cancer (Amsterdam, Netherlands). 2005;48(1):129–35.  https://doi.org/10.1016/j.lungcan.2004.10.006.CrossRefGoogle Scholar
  12. 12.
    Liang J, Bi N, Wu S, Chen M, Lv C, Zhao L, et al. Etoposide and cisplatin versus paclitaxel and carboplatin with concurrent thoracic radiotherapy in unresectable stage III non-small cell lung cancer: a multicenter randomized phase III trial. Ann Oncol. 2017;28(4):777–83.  https://doi.org/10.1093/annonc/mdx009.CrossRefPubMedGoogle Scholar
  13. 13.
    Senan S, Brade A, Wang LH, Vansteenkiste J, Dakhil S, Biesma B, et al. PROCLAIM: randomized phase III trial of pemetrexed-cisplatin or etoposide-cisplatin plus thoracic radiation therapy followed by consolidation chemotherapy in locally advanced nonsquamous non-small-cell lung cancer. J Clin Oncol. 2016;34(9):953–62.  https://doi.org/10.1200/jco.2015.64.8824.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Vokes EE, Herndon JE 2nd, Crawford J, Leopold KA, Perry MC, Miller AA, et al. Randomized phase II study of cisplatin with gemcitabine or paclitaxel or vinorelbine as induction chemotherapy followed by concomitant chemoradiotherapy for stage IIIB non-small-cell lung cancer: cancer and leukemia group B study 9431. J Clin Oncol. 2002;20(20):4191–8.  https://doi.org/10.1200/jco.2002.03.054.CrossRefPubMedGoogle Scholar
  15. 15.
    Marty M, Fumoleau P, Adenis A, Rousseau Y, Merrouche Y, Robinet G, et al. Oral vinorelbine pharmacokinetics and absolute bioavailability study in patients with solid tumors. Ann Oncol. 2001;12(11):1643–9.CrossRefGoogle Scholar
  16. 16.
    Jassem J, Kosmidis P, Ramlau R, Zarogoulidis K, Novakova L, Breton J, et al. Oral vinorelbine in combination with cisplatin: a novel active regimen in advanced non-small-cell lung cancer. Ann Oncol. 2003;14(11):1634–9.CrossRefGoogle Scholar
  17. 17.
    Jassem J, Ramlau R, Karnicka-Mlodkowska H, Krawczyk K, Krzakowski M, Zatloukal P, et al. A multicenter randomized phase II study of oral vs. intravenous vinorelbine in advanced non-small-cell lung cancer patients. Ann Oncol. 2001;12(10):1375–81.CrossRefGoogle Scholar
  18. 18.
    Ahn JS, Ahn YC, Kim JH, Lee CG, Cho EK, Lee KC, et al. Multinational randomized phase III trial with or without consolidation chemotherapy using docetaxel and cisplatin after concurrent chemoradiation in inoperable stage III non-small-cell lung cancer: KCSG-LU05-04. J Clin Oncol. 2015;33(24):2660–6.  https://doi.org/10.1200/jco.2014.60.0130.CrossRefPubMedGoogle Scholar
  19. 19.
    Bradley JD, Paulus R, Komaki R, Masters G, Blumenschein G, Schild S, et al. Standard-dose versus high-dose conformal radiotherapy with concurrent and consolidation carboplatin plus paclitaxel with or without cetuximab for patients with stage IIIA or IIIB non-small-cell lung cancer (RTOG 0617): a randomised, two-by-two factorial phase 3 study. Lancet Oncol. 2015;16(2):187–99.  https://doi.org/10.1016/s1470-2045(14)71207-0.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Krzakowski M, Provencio M, Utracka-Hutka B, Villa E, Codes M, Kuten A, et al. Oral vinorelbine and cisplatin as induction chemotherapy and concomitant chemo-radiotherapy in stage III non-small cell lung cancer: final results of an international phase II trial. J Thorac Oncol. 2008;3(9):994–1002.  https://doi.org/10.1097/JTO.0b013e31818396cb.CrossRefPubMedGoogle Scholar
  21. 21.
    Juan O, Sanchez-Hernandez A, Vazquez S, Casal J, Firvida JL, Aparisi F, et al. Full-dose cisplatin and oral vinorelbine concomitant with radiotherapy in unresectable stage III non-small cell lung cancer: a multi-center phase II study. Anticancer Res. 2014;34(4):1959–66.PubMedGoogle Scholar
  22. 22.
    Flentje M, Huber RM, Engel-Riedel W, Andreas S, Kollmeier J, Staar S, et al. 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. Strahlenther Onkol. 2016;192(4):216–22.  https://doi.org/10.1007/s00066-016-0941-8.CrossRefPubMedGoogle Scholar
  23. 23.
    Singhal N, Mislang A, Karapetis CS, Stephens S, Borg M, Woodman RJ, et al. Oral vinorelbine and cisplatin with concomitant radiotherapy in stage III non-small-cell lung cancer: an open-label phase II multicentre trial (COVeRT study). Anticancer Drugs. 2015;26(10):1083–8.  https://doi.org/10.1097/cad.0000000000000291.CrossRefPubMedGoogle Scholar
  24. 24.
    Sobin LHGM, Wittekind CH. International union against cancer (UICC) TNM classification of malignant tumors. 7th ed. Oxford: Wiley-Blackwell; 2009.Google Scholar

Copyright information

© Federación de Sociedades Españolas de Oncología (FESEO) 2018

Authors and Affiliations

  • M. Costa Rivas
    • 1
  • G. Huidobro Vence
    • 1
  • J. L. Fírvida Pérez
    • 2
  • B. Campos Balea
    • 3
  • J. García Gonzalez
    • 4
  • M. Lázaro Quintela
    • 1
  • M. Caeiro Muñoz
    • 5
  • B. Taboada Valladares
    • 6
  • J. E. Castro Gómez
    • 7
  • S. Vázquez Estevez
    • 3
  • F. J. Afonso Afonso
    • 8
  • C. Azpitarte Raposeiras
    • 9
  • M. Amenedo Gancedo
    • 10
  • J. Casal Rubio
    • 1
  1. 1.Department of Medical OncologyComplexo Hospitalario Universitario de VigoVigoSpain
  2. 2.Department of Medical OncologyComplexo Hospitalario Universitario de OurenseOurenseSpain
  3. 3.Department of Medical OncologyHospital Universitario Lucus Augusti de LugoLugoSpain
  4. 4.Department of Medical OncologyComplexo Hospitalario Universitario de Santiago de CompostelaSantiago de CompostelaSpain
  5. 5.Department of Radiation OncologyComplexo Hospitalario Universitario de VigoVigoSpain
  6. 6.Department of Radiation OncologyComplexo Hospitalario Universitario de Santiago de CompostelaSantiago de CompostelaSpain
  7. 7.Department of Radiation OncologyComplexo Hospitalario Universitario de OurenseOurenseSpain
  8. 8.Department of Medical OncologyComplexo Hospitalario Universitario de FerrolFerrolSpain
  9. 9.Department of Medical OncologyComplexo Hospitalario de PontevedraPontevedraSpain
  10. 10.Department of Medical OncologyCentro Oncológico de GaliciaA CoruñaSpain

Personalised recommendations