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Investigational New Drugs

, Volume 24, Issue 3, pp 241–248 | Cite as

Gemcitabine and vinorelbine (GV) versus cisplatin, gemcitabine and vinorelbine (CGV) as first-line treatment in advanced non small cell lung cancer: Results of a prospective randomized phase II study

  • Emilio EstebanEmail author
  • Joaquin Fra
  • Yolanda Fernández
  • Norberto Corral
  • José M. Vieitez
  • Isabel Palacio
  • José L. de Sande
  • José L. Fernández
  • Isabel Muñiz
  • Noemi Villanueva
  • Enrique Estrada
  • Beatriz Mareque
  • Esther Uña
  • José M. Buesa
  • Angel J. Lacave
  • on behalf of the Grupo Oncológico del Norte de España (“GON”)
Phase II Studies

Summary

The objective of this study was to assess whether adding cisplatin to gemcitabine/vinorelbine combination improves the clinical outcome in patients with non-small-cell lung cancer (NSCLC). Chemotherapy-naïve patients with advanced NSCLC; age ≤75 years: Karnofsky performance status ≥60%, and with adequate hematological, renal and hepatic function, were randomized into 2 treatment groups to receive Gemcitabine 1250 mg/m2 + vinorelbine 30 mg/m2 (GV group), or cisplatin 50 mg/m2 + gemcitabine 1000 mg/m2 + vinorelbine 25 mg/m2 (CGV group). All drugs were administered on days 1 and 8 every three weeks: From September 1999 to March 2003, 114 patients were enrolled. No statistically significant difference was observed in GV vs CGV group in objective response (37 versus 47%, respectively; P = 0.5), median time to progression (5 versus 5.8 months; P = 0.6), overall survival (9 versus 10 months; P = 0.9) and 1-year survival (26 versus 28%; P = 0.9). Conversely, toxicities were significantly higher for CGV, including grade 3–4 neutropenia (24 versus 45%); neutropenic fever (4 versus 14%, including one toxic death); grade 3–4 thrombocytopenia (2 versus 14%); and grade 3–4 emesis (2 versus 14%). Our results suggest that the combination of gemcitabine and vinorelbine is less toxic than three-drug combination with cisplatin while showing similar efficacy.

Key Words

Gemcitabine vinorelbine cisplatin NSCLC 

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References

  1. 1.
    Gatzemeier U, Shepherd FA, Le Chevalier T, Weynants P, Cottier B, Groen HJ, Rosso R, Mattson K, Cortes-Funes H, Tonato M, Burkes RL, Gottfried M, Voi M: Activity of gemcitabine in patients with non-small cell lung cancer: A multicentre extended phase II study. Eur J Cancer 32A: 243–248, 1996CrossRefPubMedGoogle Scholar
  2. 2.
    Abratt RP, Bezwoda WR, Falkson G, Goedhals L, Hacking D, Rugg TA: Efficacy and safety profile of gemcitabine in non-small cell lung cancer: A phase II study. J Clin Oncol 12:1535–1540, 1994PubMedGoogle Scholar
  3. 3.
    Anderson H, Lund B, Bach F, Thatcher N, Walling J, Hansen HH: Single-agent activity of weekly gemcitabine in advanced non-small cell lung cancer: A phase II study. J Clin Oncol 12: 1821–1826, 1994PubMedGoogle Scholar
  4. 4.
    Depierre A, Lemarie E, Dabouis G, Garnier G, Jacoulet P, Dalphin JC: A phase II study of Navelbine (vinorelbine) in the treatment of non-small cell lung cancer. Am J Clin Oncol 14: 115–119, 1991PubMedGoogle Scholar
  5. 5.
    Manegold C, Bergman B, Chemaissani A, Dornoff W, Drings P, Kellokumpu-Lehtinen P, Liippo K, Mattson K, van Pawel J, Ricci S, Sederholm C, Stahel RA, Wagenius G, van Walree N, ten Bokkel-Huinink W: Single-agent gemcitabine versus cisplatin-etoposide: Early results of a randomized phase II study in locally advanced or metastatic non-small-cell lung cancer. Ann Oncol 8: 525–529, 1997CrossRefPubMedGoogle Scholar
  6. 6.
    Le Chevalier T, Brisgand D, Douillard JY, Pujol JL, Alberola V, Monnier A, Riviere A, Lianes P, Chomy P, Cigolari S: Randomized study of vinorelbine and cisplatin versus vindesine and cisplatin versus vinorelbine alone in advanced non-small-cell lung cancer: Results of a European multicenter trial including 612 patients. J Clin Oncol. 12: 360–367, 1994PubMedGoogle Scholar
  7. 7.
    (Anonymous) Effects of vinorelbine on quality of life and survival of elderly patients with advanced non-small-cell lung cancer. The Elderly Lung Cancer Vinorelbine Italian Study Group. J Natl Cancer Inst 91: 66–72, 1999CrossRefGoogle Scholar
  8. 8.
    Anderson H, Cottier B, Nicolson M, Milroy R, Maughan T, Bond M, Falk S, Burt P, Carmichael J, Thatcher N: Phase III study of gemcitabine (Gemzar®) versus best supportive care (BSC) in advanced non-small cell lung cancer (NSCLC). Abstract Lung Cancer 18(suppl 1): 9(24), 1997Google Scholar
  9. 9.
    Perng RP, Chen YM, Ming-Liu J, Tsai CM, Lin WC, Yang KY, Whang-Peng J: Gemcitabine versus the combination of cisplatin and etoposide in patients with inoperable non-small-cell lung cancer in a phase II randomized study. J Clin Oncol 15: 2097–2102, 1997PubMedGoogle Scholar
  10. 10.
    Cardenal F, Lopez-Cabrerizo MP, Anton A, Alberola V, Massuti B, Carrato A, Barneto I, Lomas M, Garcia M, Lianes P, Montalar J, Vadell C, Gonzalez-Larriba JL, Nguyen B, Artal A, Rosell R: Randomized phase III study of gemcitabine-cisplatin versus etoposide-cisplatin in the treatment of locally advanced or metastatic non-small-cell lung cancer. J Clin Oncol 17: 12–18, 1999PubMedGoogle Scholar
  11. 11.
    Cigolari S, Gridelli C, Frontini L: Gemcitabine + vinorelbine (GEMVIN) in the treatment of advanced non-small cell lung cancer (NSCLC). Sequential phase I and phase II trials. Abstract. Ann Oncol 9(suppl 4): 87(419P), 1998Google Scholar
  12. 12.
    Lorusso V, Carpagnano F, Di Rienzo G, Cinieri S, Catino A, Mancarella S, Cisternino ML, Orlando S, Napoli G, Paradiso A, Brandi M, Caporusso L, De Lena M: Combination of gemcitabine and vinorelbine in non-small cell lung cancer (NSCLC). A phase I-II study. Abstract. Proc Am Soc Clin Oncol 16: 453a(1628), 1997Google Scholar
  13. 13.
    Esteban E, Fra J, Corral N, Valle M, Carrasco J, Sala M, Puerta J, Estrada E, Palacio I, Vieitez JM, Buesa JM, Lacave AJ: Phase I/II study of gemcitabine plus vinorelbine in non-small cell lung cancer. Invest New Drugs 20: 73–82, 2002CrossRefPubMedGoogle Scholar
  14. 14.
    Albain KS, Crowley JJ, LeBlanc M, Livingston RB: Survival determinants in extensive-stage non-small-cell lung cancer: the Southwest Oncology Group experience. J Clin Oncol 9: 1618–1626, 1991PubMedGoogle Scholar
  15. 15.
    (Anonymous) Chemotherapy in non-small cell lung cancer: a meta-analysis using updated data on individual patients from 52 randomized clinical trials. Non-Small Cell Lung Cancer Collaborative Group. Br Med J 311: 899–909, 1995Google Scholar
  16. 16.
    Gandara DR, Crowley J, Livingston RB, Perez EA, Taylor CW, Weiss G, Neefe JR, Hutchins LF, Roach RW, Grunberg SM: Evaluation of cisplatin intensity in metastatic non-small cell lung cancer: a phase III study of the Southwest Oncology Group. J Clin Oncol 11: 873–878, 1993PubMedGoogle Scholar
  17. 17.
    Esteban E, Fra J, Sala M, Carrasco J, Corral N, Vieitez JM, Estrada E, Palacio I, Buesa JM, Lacave AJ: Phase I/II study of gemcitabine plus Vinorelbine and Cisplatin in Non-Small cell Lung Cancer. Invest New Drugs 20: 317–326, 2002CrossRefPubMedGoogle Scholar
  18. 18.
    Frasci G, Panza N, Comella P, Nicolella GP, Natale M, Pacilio C, Gravina A, Caputi V, Botti G, Comella G: Cisplatin, gemcitabine, and vinorelbine in locally advanced or metastatic non-small cell lung cancer. Ann Oncol 8: 1045–1048, 1997CrossRefPubMedGoogle Scholar
  19. 19.
    Schaid DJ, Wieand S, Therneau TM: Optimal two-stage screening designs for survival comparasions. Biometrika 77: 507–513, 1990CrossRefGoogle Scholar
  20. 20.
    World Health Organization Handbook for reporting results of cancer treatment. WHO offset publication #48 Geneva 1979Google Scholar
  21. 21.
    Mehta CR, Patel NR: A network algorithm for performing Fisher’s exact test in r x c contingency tables. J Am Stat Assoc 78: 427–434, 1983Google Scholar
  22. 22.
    Winer BJ: Statistical principles in experimental design. McGraw-Hill. London 1970Google Scholar
  23. 23.
    Kruskal-Wallis. Nonparametric statistical inference. JD Gibbons S. Chakrabots. Editors. M. Dekker 1992.Google Scholar
  24. 24.
    Kaplan EL, Meier P: Nonparametric estimation from incomplete observation. J Am Stat Assoc 53: 457–481, 1958Google Scholar
  25. 25.
    Cardenal F, Lopez-Cabrerizo MP, Anton A, Alberola V, Massuti B, Carrato A, Barneto I, Lomas M, Garcia M, Lianes P, Montalar J, Vadell C, Gonzalez-Larriba JL, Nguyen B, Artal A, Rosell R: Randomized phase III study of gemcitabine-cisplatin versus etoposide-cisplatin in the treatment of locally advanced or metastatic non-small cell lung cancer. J Clin Oncol 17: 12–18, 1999PubMedGoogle Scholar
  26. 26.
    Crino L, Scagliotti GV, Ricci S, De Marinis F, Rinaldi M, Gridelli C, Ceribelli A, Bianco R, Marangolo M, Di Costanzo F, Sassi M, Barni S, Ravaioli A, Adamo V, Portalone L, Cruciani G, Masotti A, Ferrara G, Gozzelino F, Tonato M: Gemcitabine and cisplatin versus mitomycin, ifosfamide, and cisplatin in advanced non-small cell lung cancer: A randomized phase III study of the Italian Lung Cancer Project. J Clin Oncol 17: 3522–3530, 1999PubMedGoogle Scholar
  27. 27.
    Giaccone G, Splinter TA, Debruyne C, Kho GS, Lianes P, van Zandwijk N, Pennucci MC, Scagliotti G, van Meerbeeck J, van Hoesel Q, Curran D, Sahmoud T, Postmus PE: Randomized study of paclitaxel-cisplatin versus cisplatin-teniposide in patients with advanced non-small cell lung cancer. The European Organization for Research and Treatment of Lung Cancer Cooperative Group. J Clin Oncol 16: 2133–2141, 1998PubMedGoogle Scholar
  28. 28.
    Schiller JH, Harrington D, Belani CP, Langer C, Sandler A, Krook J, Zhu J, Johnson DH: Eastern Cooperative Oncology Group. Comparison of four chemotherapy regimens for advanced non-small cell lung cancer. N Engl J Med 346: 92–98, 2002CrossRefPubMedGoogle Scholar
  29. 29.
    Smit EF, van Meerbeeck JP, Lianes P, Debruyne C, Legrand C, Schramel F, Smit H, Gaafar R, Biesma B, Manegold C, Neymark N, Giaccone G: European organization for research and treatment of cancer lung cancer group. Three-Arm Randomized study of two Cisplatin-Based Regimens and Paclitaxel plus Gemcitabine in advanced non-small-cell lung cancer. A phase III trial of the European Organization for Research and Treatment of Cancer Lung Cancer Group-EORTC 08975. J Clin Oncol 21: 3909–3917, 2003CrossRefPubMedGoogle Scholar
  30. 30.
    Scagliotti GV, De Marinis F, Rinaldi M, Crino L, Gridelli C, Ricci S, Matano E, Boni C, Marangolo M, Failla G, Altavilla G, Adamo V, Ceribelli A, Clerici M, Di Costanzo F, Frontini L, Tonato M: Italian lung cancer project. Phase III randomized trial comparing three platinum-based doublets in advanced non-small cell lung cancer. J Clin Oncol 20:4285–4291, 2002CrossRefPubMedGoogle Scholar
  31. 31.
    Fossella F, Pereira JR, von Pawel J, Pluzanska A, Gorbounova V, Kaukel E, Mattson KV, Ramlau R, Szczesna A, Fidias P, Millward M, Belani CP: Randomized, multinational, phase III study of docetaxel plus platinum combinations versus vinorelbine plus cisplatin for advanced non-small-cell lung cancer: The TAX 326 study Group. J Clin Oncol 21: 3016–3024, 2003CrossRefPubMedGoogle Scholar
  32. 32.
    Comella P, Frasci G, Panza N, Manzione L, Lorusso V, Di Rienzo G, Cioffi R, De Cataldis G, Maiorino L, Bilancia D, Nicolella G, Natale M, Carpagnano F, Pacilio C, De Lena M, Bianco A, Comella G: Cisplatin, gemcitabine, and vinorelbine combination therapy in advanced non-small-cell lung cancer (NSCLC): A phase II randomized study of Southern Italy Cooperative Oncology Group phase II randomized study. J Clin Oncol 17: 1526–1534, 1999PubMedGoogle Scholar
  33. 33.
    Laack E, Dickgreber N, Muller T, Knuth A, Benk J, Lorenz C, Gieseler F, Durk H, Engel-Riedel W, Dalhoff K, Kortsik C, Graeven U, Burk M, Dierlamm T, Welte T, Burkholder I, Edler L, Hossfeld DK: German and swiss lung cancer study group. Randomized phase III study of gemcitabine and vinorelbine versus gemcitabine, vinorelbine, and cisplatin in the treatment of advanced non-small-cell lung cancer: From the German and Swiss Lung Cancer Study Group. J Clin Oncol 15(22): 2348–2356, 2004CrossRefGoogle Scholar
  34. 34.
    Alberola V, Camps C, Provencio M, Isla D, Rosell R, Vadell C, Bover I, Ruiz-Casado A, Azagra P, Jimenez U, Gonzalez-Larriba JL, Diz P, Cardenal F, Artal A, Carrato A, Morales S, Sanchez JJ, de las Penas R, Felip E, Lopez-Vivanco G: Spanish lung cancer group. Cisplatin/Gemcitabine versus a Cisplatin-Based Triplet versus Non-Platinum Sequential Doublets in Advanced Non-Small-Cell Lung Cancer: A Spanish Lung Cancer Group Phase III Randomized Trial. J Clin Oncol 21: 3207–3213, 2003CrossRefPubMedGoogle Scholar
  35. 35.
    Gridelli C, Gallo C, Shepherd FA, Illiano A, Piantedosi F, Robbiati SF, Manzione L, Barbera S, Frontini L, Veltri E, Findlay B, Cigolari S, Myers R, Ianniello GP, Gebbia V, Gasparini G, Fava S, Hirsh V, Bezjak A, Seymour L, Perrone F: Gemcitabine plus Vinorelbine compared with Cisplatin plus vinorelbine or Cisplatin plus Gemcitabine chemotherapy for advanced non-small cell lung cancer: A phase III trial of the Italian GEMVIN investigators and the National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol 21: 3025–3034, 2003CrossRefPubMedGoogle Scholar
  36. 36.
    Comella P, Frasci G, Panza N, Manzione L, De Cataldis G, Cioffi R, Maiorino L, Micillo E, Lorusso V, Di Rienzo G, Filippelli G, Lamberti A, Natale M, Bilancia D, Nicolella G, Di Nota A, Comella G: Randomized trial comparing cisplatin, gemcitabine, and vinorelbine with either Cisplatin and Gemcitabine or Cisplatin and Vinorelbine in Non-Small-Cell Lung Cancer: Interim Analysis of a phase III trial of the Southern Italy Cooperative Oncology Group. J Clin Oncol 18: 1451–1457, 2000.PubMedGoogle Scholar
  37. 37.
    Georgoulias V, Papadakis E, Alexopoulos A, Tsiafaki X, Rapti A, Veslemes M, Palamidas P, Vlachonikolis I: Greek Oncology Cooperative Group (GOCG) for Lung Cancer. Platinum-based and non-platinum-based chemotherapy in advanced non-small-cell lung cancer. Lancet 357: 1478–1484, 2001CrossRefPubMedGoogle Scholar
  38. 38.
    D’Addario G, Pintillie M, Cerny T, Feld R, Leighl N, Shepherd FA: Platinum-based versus non-platinum-based chemotherapy in advanced non-small cell lung cancer (NSCLC): A meta-analysis of the published literature. Lung Cancer 41(2): 0–233, 2003Google Scholar
  39. 39.
    Pfister DG, Johnson DH, Azzoli CG, Sause W, Smith TJ, Baker S Jr, Olak J, Stover D, Strawn JR, Turrisi AT, Somerfield MR: American Society of Clinical Oncology Treatment of Unresectable Non-Small-Cell Lung Cancer Guidelines: Update 2003. J Clin Oncol 22: 330–353, 2004CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science + Business Media, LLC 2005

Authors and Affiliations

  • Emilio Esteban
    • 1
    • 4
    Email author
  • Joaquin Fra
    • 1
  • Yolanda Fernández
    • 1
  • Norberto Corral
    • 1
  • José M. Vieitez
    • 1
  • Isabel Palacio
    • 1
  • José L. de Sande
    • 2
  • José L. Fernández
    • 3
  • Isabel Muñiz
    • 1
  • Noemi Villanueva
    • 1
  • Enrique Estrada
    • 1
  • Beatriz Mareque
    • 1
  • Esther Uña
    • 1
  • José M. Buesa
    • 1
  • Angel J. Lacave
    • 1
  • on behalf of the Grupo Oncológico del Norte de España (“GON”)
  1. 1.Clinical Oncology Services of the Hospital Central de Asturias, (Oviedo)Spain
  2. 2.Clinical Oncology Services of the Hospital de LeónSpain
  3. 3.Clinical Oncology Services of the Hospital de PonferradaSpain
  4. 4.Clinical Oncology Services of the Hospital Central de AsturiasOviedoSpain

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