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. 2001 Nov;85(10):1444–1451. doi: 10.1054/bjoc.2001.2114

A three-arm phase III randomised trial assessing, in patients with extensive-disease small-cell lung cancer, accelerated chemotherapy with support of haematological growth factor or oral antibiotics

J P Sculier 1, M Paesmans 1, J Lecomte 1, O Van Cutsem 1, J J Lafitte 1, T Berghmans 1, G Koumakis 1, M C Florin 1, J Thiriaux 1, J Michel 1, V Giner 1, M C Berchier 1, P Mommen 1, V Ninane 1, J Klastersky 1; the European Lung Cancer Working Party 1
PMCID: PMC2363948  PMID: 11720426

Abstract

The European Lung Cancer Working Party (ELCWP) designed a 3-arm phase III randomised trial to determine the role of accelerated chemotherapy in extensive-disease (ED) small-cell lung cancer (SCLC). Eligible patients were randomised between the 3 following arms: (A) Standard chemotherapy with 6 courses of EVI (epirubicin 60 mg m−2, vindesine 3 mg m−2, ifosfamide 5 g m−2; all drugs given on day 1 repeated every three weeks. (B) Accelerated chemotherapy with EVI administered every 2 weeks and GM-CSF support. (C) Accelerated chemotherapy with EVI and oral antibiotics (cotrimoxazole). Primary endpoint was survival. 233 eligible patients were randomised. Chemotherapy could be significantly accelerated in arm B with increased absolute dose-intensity. Best response rates, in the population of evaluable patients, were, respectively for arm A, B and C, 59%, 76% and 70%. The response rate was significantly higher in arm B in comparison to arm A (P = 0.04). There was, however, no survival difference with respective median duration and 2-year rate of 286 days and 5% for arm A, 264 days and 6% for arm B and 264 days and 6% for arm C. Severe thrombopenia occurred more frequently in arm B but without an increased rate of bleeding. Non-severe infections were more frequent in arm B and severe infections were less frequent in arm C. Our trial failed to demonstrate, in ED-SCLC, a survival benefit of chemotherapy acceleration by using GM-CSF support.   http://www.bjcancer.com

Keywords: small-cell lung cancer, GM-CSF, accelerated chemotherapy

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Footnotes

The following institutions participated in the trial: Institut Jules Bordet (JP Sculier, M Paesmans, T Berghmans, P Mommen, J Klastersky,), Brussels, Belgium; Hôpital Saint Pierre (R Sergijsels, V Ninane), Brussels, Belgium; CHU de Charleroi (J Thiriaux, J Lecomte), Charleroi, Belgium; Clinique Saint Luc (O Van Cutsem), Namur, Belgium; CHU de Lille, Hôpital Calmette (JJ Lafitte), Lille, France; Hellenic Cancer Institute (A Efremidis, G Koumakis), Athens, Greece; CH de Douai (MC Florin, E Maetz), Douai, France; CH de Tivoli (J Michel), Tivoli, Belgium; Hospital de Sagunto (V Giner Marco), Valencia, Spain; Hôpital d'Hayange (MC Berchier), Hayange, France; CH de Roubaix (F Kroll), Roubaix, France; CHUA Vésale (D Brohée), Montignies-le-Tilleul, Belgium; CHI de Montfermeil (C Zacharias), Montfermeil, France; IMC Mutualités Socialistes (A Tagnon), Tournai, Belgium; Groupe Médical St Rémi (G Bureau), Reims, France; Hôpital de Warquingnies (P Libert, M Richez), Warquignies, Belgium; CH. de Mons (P Recloux), Mons, Belgium; Clinique de la Louvière (F Fortin), Lille, France; CH Dr Schaffner (J Amourette), Lens, France; Clinique Louis Caty (V Richard), Baudour, Belgium; CH du Pays d'Ath (P Ravez), Ath, Belgium; Klinika radiotherapie a onkologie (J Baumöhl), Kosice, Slovakia; CH de Tourcoing (X Ficheroulle), Tourcoing, France; Cabinet de Pneumologie (Y Watrigant), Tourcoing, France; Hôpital Duchenne (JL Crepin), Boulogne-sur-Mer, France; Hôpital Brugmann (A Drowart), Brussels, Belgium; Hôpital de Braine l'Alleud (C Finet), Braine L'Alleud, Belgium.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Arriagada R., Le Chevalier T., Pignon J. P., Rivière A., Monnet I., Chomy P., Tuchais C., Tarayre M., Ruffié P. Initial chemotherapeutic doses and survival in patients with limited small-cell lung cancer. N Engl J Med. 1993 Dec 16;329(25):1848–1852. doi: 10.1056/NEJM199312163292504. [DOI] [PubMed] [Google Scholar]
  2. Bunn P. A., Jr, Crowley J., Kelly K., Hazuka M. B., Beasley K., Upchurch C., Livingston R., Weiss G. R., Hicks W. J., Gandara D. R. Chemoradiotherapy with or without granulocyte-macrophage colony-stimulating factor in the treatment of limited-stage small-cell lung cancer: a prospective phase III randomized study of the Southwest Oncology Group. J Clin Oncol. 1995 Jul;13(7):1632–1641. doi: 10.1200/JCO.1995.13.7.1632. [DOI] [PubMed] [Google Scholar]
  3. Crawford J., Ozer H., Stoller R., Johnson D., Lyman G., Tabbara I., Kris M., Grous J., Picozzi V., Rausch G. Reduction by granulocyte colony-stimulating factor of fever and neutropenia induced by chemotherapy in patients with small-cell lung cancer. N Engl J Med. 1991 Jul 18;325(3):164–170. doi: 10.1056/NEJM199107183250305. [DOI] [PubMed] [Google Scholar]
  4. Figueredo A. T., Hryniuk W. M., Strautmanis I., Frank G., Rendell S. Co-trimoxazole prophylaxis during high-dose chemotherapy of small-cell lung cancer. J Clin Oncol. 1985 Jan;3(1):54–64. doi: 10.1200/JCO.1985.3.1.54. [DOI] [PubMed] [Google Scholar]
  5. Freedman L. S. Tables of the number of patients required in clinical trials using the logrank test. Stat Med. 1982 Apr-Jun;1(2):121–129. doi: 10.1002/sim.4780010204. [DOI] [PubMed] [Google Scholar]
  6. Freedman L. S., White S. J. On the use of Pocock and Simon's method for balancing treatment numbers over prognostic factors in the controlled clinical trial. Biometrics. 1976 Sep;32(3):691–694. [PubMed] [Google Scholar]
  7. Hamm J., Schiller J. H., Cuffie C., Oken M., Fisher R. I., Shepherd F., Kaiser G. Dose-ranging study of recombinant human granulocyte-macrophage colony-stimulating factor in small-cell lung carcinoma. J Clin Oncol. 1994 Dec;12(12):2667–2676. doi: 10.1200/JCO.1994.12.12.2667. [DOI] [PubMed] [Google Scholar]
  8. Johnson D. H. Management of small cell lung cancer: current state of the art. Chest. 1999 Dec;116(6 Suppl):525S–530S. doi: 10.1378/chest.116.suppl_3.525s. [DOI] [PubMed] [Google Scholar]
  9. Lieschke G. J., Burgess A. W. Granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor (1). N Engl J Med. 1992 Jul 2;327(1):28–35. doi: 10.1056/NEJM199207023270106. [DOI] [PubMed] [Google Scholar]
  10. Lieschke G. J., Burgess A. W. Granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor (2). N Engl J Med. 1992 Jul 9;327(2):99–106. doi: 10.1056/NEJM199207093270207. [DOI] [PubMed] [Google Scholar]
  11. Luce S., Paesmans M., Berghmans T., Castaigne C., Sotiriou C., Vermylen P., Sculier J. P. Revue critique des études randomisées évaluant le rôle de la radiothérapie thoracique adjuvante à la chimiothérapie dans le traitement du cancer bronchique à petites cellules au stade limité. Rev Mal Respir. 1998 Oct;15(5):633–641. [PubMed] [Google Scholar]
  12. Mascaux C., Paesmans M., Berghmans T., Branle F., Lafitte J. J., Lemaitre F., Meert A. P., Vermylen P., Sculier J. P., European Lung Cancer Working Party (ELCWP) A systematic review of the role of etoposide and cisplatin in the chemotherapy of small cell lung cancer with methodology assessment and meta-analysis. Lung Cancer. 2000 Oct;30(1):23–36. doi: 10.1016/s0169-5002(00)00127-6. [DOI] [PubMed] [Google Scholar]
  13. Ozer H., Armitage J. O., Bennett C. L., Crawford J., Demetri G. D., Pizzo P. A., Schiffer C. A., Smith T. J., Somlo G., Wade J. C. 2000 update of recommendations for the use of hematopoietic colony-stimulating factors: evidence-based, clinical practice guidelines. American Society of Clinical Oncology Growth Factors Expert Panel. J Clin Oncol. 2000 Oct 15;18(20):3558–3585. doi: 10.1200/JCO.2000.18.20.3558. [DOI] [PubMed] [Google Scholar]
  14. Paesmans M., Sculier J. P., Lecomte J., Thiriaux J., Libert P., Sergysels R., Bureau G., Dabouis G., Van Cutsem O., Mommen P. Prognostic factors for patients with small cell lung carcinoma: analysis of a series of 763 patients included in 4 consecutive prospective trials with a minimum follow-up of 5 years. Cancer. 2000 Aug 1;89(3):523–533. doi: 10.1002/1097-0142(20000801)89:3<523::aid-cncr7>3.0.co;2-6. [DOI] [PubMed] [Google Scholar]
  15. Pignon J. P., Arriagada R., Ihde D. C., Johnson D. H., Perry M. C., Souhami R. L., Brodin O., Joss R. A., Kies M. S., Lebeau B. A meta-analysis of thoracic radiotherapy for small-cell lung cancer. N Engl J Med. 1992 Dec 3;327(23):1618–1624. doi: 10.1056/NEJM199212033272302. [DOI] [PubMed] [Google Scholar]
  16. Pujol J. L., Douillard J. Y., Rivière A., Quoix E., Lagrange J. L., Berthaud P., Bardonnet-Comte M., Polin V., Gautier V., Milleron B. Dose-intensity of a four-drug chemotherapy regimen with or without recombinant human granulocyte-macrophage colony-stimulating factor in extensive-stage small-cell lung cancer: a multicenter randomized phase III study. J Clin Oncol. 1997 May;15(5):2082–2089. doi: 10.1200/JCO.1997.15.5.2082. [DOI] [PubMed] [Google Scholar]
  17. Sculier J. P., Berghmans T., Castaigne C., Luce S., Sotiriou C., Vermylen P., Paesmans M. Maintenance chemotherapy for small cell lung cancer: a critical review of the literature. Lung Cancer. 1998 Feb;19(2):141–151. doi: 10.1016/s0169-5002(97)00084-6. [DOI] [PubMed] [Google Scholar]
  18. Sculier J. P., Klastersky J. High-dose chemotherapy of small-cell lung cancer with and without bone marrow transplantation. Cancer Treat Res. 1989;45:259–274. doi: 10.1007/978-1-4613-1593-3_15. [DOI] [PubMed] [Google Scholar]
  19. Sculier J. P., Klastersky J., Libert P., Ravez P., Thiriaux J., Lecomte J., Bureau G., Vandermoten G., Dabouis G., Michel J. A randomized study comparing etoposide and vindesine with or without cisplatin as induction therapy for small cell lung cancer. EORTC Lung Cancer Working Party. Ann Oncol. 1990;1(2):128–133. doi: 10.1093/oxfordjournals.annonc.a057690. [DOI] [PubMed] [Google Scholar]
  20. Sculier J. P., Paesmans M., Bureau G., Dabouis G., Libert P., Vandermoten G., Van Cutsem O., Berchier M. C., Ries F., Michel J. Multiple-drug weekly chemotherapy versus standard combination regimen in small-cell lung cancer: a phase III randomized study conducted by the European Lung Cancer Working Party. J Clin Oncol. 1993 Oct;11(10):1858–1865. doi: 10.1200/JCO.1993.11.10.1858. [DOI] [PubMed] [Google Scholar]
  21. Sculier J. P., Paesmans M., Bureau G., Giner V., Lecomte J., Michel J., Berchier M. C., Van Cutsem O., Küstner U., Kroll F. Randomized trial comparing induction chemotherapy versus induction chemotherapy followed by maintenance chemotherapy in small-cell lung cancer. European Lung Cancer Working Party. J Clin Oncol. 1996 Aug;14(8):2337–2344. doi: 10.1200/JCO.1996.14.8.2337. [DOI] [PubMed] [Google Scholar]
  22. Steward W. P., von Pawel J., Gatzemeier U., Woll P., Thatcher N., Koschel G., Clancy L., Verweij J., de Wit R., Pfeifer W. Effects of granulocyte-macrophage colony-stimulating factor and dose intensification of V-ICE chemotherapy in small-cell lung cancer: a prospective randomized study of 300 patients. J Clin Oncol. 1998 Feb;16(2):642–650. doi: 10.1200/JCO.1998.16.2.642. [DOI] [PubMed] [Google Scholar]
  23. Thatcher N., Girling D. J., Hopwood P., Sambrook R. J., Qian W., Stephens R. J. Improving survival without reducing quality of life in small-cell lung cancer patients by increasing the dose-intensity of chemotherapy with granulocyte colony-stimulating factor support: results of a British Medical Research Council Multicenter Randomized Trial. Medical Research Council Lung Cancer Working Party. J Clin Oncol. 2000 Jan;18(2):395–404. doi: 10.1200/JCO.2000.18.2.395. [DOI] [PubMed] [Google Scholar]
  24. Thatcher N. New perspectives in lung cancer. 4. Haematopoietic growth factors and lung cancer treatment. Thorax. 1992 Feb;47(2):119–126. doi: 10.1136/thx.47.2.119. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Trillet-Lenoir V., Green J. A., Manegold C., Von Pawel J., Gatzemeier U., Lebeau B., Depierre A., Johnson P., Decoster G., Matcham J. Recombinant granulocyte colony stimulating factor in the treatment of small cell lung cancer: a long-term follow-up. Eur J Cancer. 1995 Nov;31A(12):2115–2116. doi: 10.1016/0959-8049(95)00370-3. [DOI] [PubMed] [Google Scholar]
  26. Trillet-Lenoir V., Green J., Manegold C., Von Pawel J., Gatzemeier U., Lebeau B., Depierre A., Johnson P., Decoster G., Tomita D. Recombinant granulocyte colony stimulating factor reduces the infectious complications of cytotoxic chemotherapy. Eur J Cancer. 1993;29A(3):319–324. doi: 10.1016/0959-8049(93)90376-q. [DOI] [PubMed] [Google Scholar]
  27. Warde P., Payne D. Does thoracic irradiation improve survival and local control in limited-stage small-cell carcinoma of the lung? A meta-analysis. J Clin Oncol. 1992 Jun;10(6):890–895. doi: 10.1200/JCO.1992.10.6.890. [DOI] [PubMed] [Google Scholar]
  28. de Jongh C. A., Wade J. C., Finley R. S., Joshi J. H., Aisner J., Wiernik P. H., Schimpff S. C. Trimethoprim/sulfamethoxazole versus placebo: a double-blind comparison of infection prophylaxis in patients with small cell carcinoma of the lung. J Clin Oncol. 1983 May;1(5):302–307. doi: 10.1200/JCO.1983.1.5.302. [DOI] [PubMed] [Google Scholar]

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