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. 2002 Jan;57(1):20–28. doi: 10.1136/thorax.57.1.20

Clinical and cost effectiveness of paclitaxel, docetaxel, gemcitabine, and vinorelbine in non-small cell lung cancer: a systematic review

A Clegg 1, D Scott 1, P Hewitson 1, M Sidhu 1, N Waugh 1
PMCID: PMC1746188  PMID: 11809985

Abstract

Background: Lung cancer remains a devastating disease with few effective treatment options. Recent developments in chemotherapy have led to cautious optimism. This paper reviews the evidence on the clinical and cost effectiveness of four of the new generation drugs for patients with lung cancer.

Methods: A systematic review of randomised controlled trials (RCTs) identified from 11 electronic databases (including Medline, Cochrane library and Embase), reference lists and contact with experts and industry was performed to assess clinical effectiveness of paclitaxel, docetaxel, gemcitabine and vinorelbine. Clinical effectiveness was assessed using the outcomes of patient survival, quality of life, and adverse effects. Cost effectiveness was assessed by development of a costing model and presented as incremental cost per life year saved (LYS) compared with best supportive care (BSC).

Results: Of the 33 RCTs included, five were judged to be of good quality, 10 of adequate quality, and 18 of poor quality. Gemcitabine, paclitaxel, and vinorelbine as first line treatment and docetaxel as second line treatment appear to be more beneficial for non-small cell lung cancer than BSC and older chemotherapy agents, increasing patient survival by 2–4 months against BSC and some comparator regimes. These gains in survival do not appear to be at the expense of quality of life. Survival gains were delivered at reasonable levels of incremental cost effectiveness for vinorelbine, vinorelbine with cisplatin, gemcitabine, gemcitabine with cisplatin, and paclitaxel with cisplatin regimens compared with BSC.

Conclusion: Although the clinical benefits of the new drugs appear relatively small, their benefit to patients with lung cancer appears to be worthwhile and cost effective.

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Selected References

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  1. Anderson H., Hopwood P., Stephens R. J., Thatcher N., Cottier B., Nicholson M., Milroy R., Maughan T. S., Falk S. J., Bond M. G. Gemcitabine plus best supportive care (BSC) vs BSC in inoperable non-small cell lung cancer--a randomized trial with quality of life as the primary outcome. UK NSCLC Gemcitabine Group. Non-Small Cell Lung Cancer. Br J Cancer. 2000 Aug;83(4):447–453. doi: 10.1054/bjoc.2000.1307. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Baldini E., Tibaldi C., Ardizzoni A., Salvati F., Antilli A., Portalone L., Barbera S., Romano F., De Marinis F., Migliorino M. R. Cisplatin-vindesine-mitomycin (MVP) vs cisplatin-ifosfamide-vinorelbine (PIN) vs carboplatin-vinorelbine (CaN) in patients with advanced non-small-cell lung cancer (NSCLC): a FONICAP randomized phase II study. Italian Lung Cancer Task Force (FONICAP). Br J Cancer. 1998 Jun;77(12):2367–2370. doi: 10.1038/bjc.1998.393. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bero L. A., Rennie D. Influences on the quality of published drug studies. Int J Technol Assess Health Care. 1996 Spring;12(2):209–237. doi: 10.1017/s0266462300009582. [DOI] [PubMed] [Google Scholar]
  4. Berthelot J. M., Will B. P., Evans W. K., Coyle D., Earle C. C., Bordeleau L. Decision framework for chemotherapeutic interventions for metastatic non-small-cell lung cancer. J Natl Cancer Inst. 2000 Aug 16;92(16):1321–1329. doi: 10.1093/jnci/92.16.1321. [DOI] [PubMed] [Google Scholar]
  5. Bonomi P., Kim K., Fairclough D., Cella D., Kugler J., Rowinsky E., Jiroutek M., Johnson D. Comparison of survival and quality of life in advanced non-small-cell lung cancer patients treated with two dose levels of paclitaxel combined with cisplatin versus etoposide with cisplatin: results of an Eastern Cooperative Oncology Group trial. J Clin Oncol. 2000 Feb;18(3):623–631. doi: 10.1200/JCO.2000.18.3.623. [DOI] [PubMed] [Google Scholar]
  6. Cardenal F., López-Cabrerizo M. P., Antón A., Alberola V., Massuti B., Carrato A., Barneto I., Lomas M., García M., Lianes P. 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. 1999 Jan;17(1):12–18. doi: 10.1200/JCO.1999.17.1.12. [DOI] [PubMed] [Google Scholar]
  7. Chang A. Y., Kim K., Glick J., Anderson T., Karp D., Johnson D. Phase II study of taxol, merbarone, and piroxantrone in stage IV non-small-cell lung cancer: The Eastern Cooperative Oncology Group Results. J Natl Cancer Inst. 1993 Mar 3;85(5):388–394. doi: 10.1093/jnci/85.5.388. [DOI] [PubMed] [Google Scholar]
  8. Colucci G., Gebbia V., Galetta D., Riccardi F., Cariello S., Gebbia N. Cisplatin and vinorelbine followed by ifosfamide plus epirubicin vs the opposite sequence in advanced unresectable stage III and metastatic stage IV non-small-cell lung cancer: a prospective randomized study of the Southern Italy Oncology Group (GOIM). Br J Cancer. 1997;76(11):1509–1517. doi: 10.1038/bjc.1997.586. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Comella P., Frasci G., De Cataldis G., Panza N., Cioffi R., Curcio C., Belli M., Bianco A., Ianniello G., Maiorino L. Cisplatin/carboplatin + etoposide + vinorelbine in advanced non-small-cell lung cancer: a multicentre randomised trial. Gruppo Oncologico Campano. Br J Cancer. 1996 Dec;74(11):1805–1811. doi: 10.1038/bjc.1996.634. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Comella P., Frasci G., Panza N., Manzione L., De Cataldis G., Cioffi R., Maiorino L., Micillo E., Lorusso V., Di Rienzo G. Randomized trial comparing cisplatin, gemcitabine, and vinorelbine with either cisplatin and gemcitabine or cisplatin and vinorelbine in advanced non-small-cell lung cancer: interim analysis of a phase III trial of the Southern Italy Cooperative Oncology Group. J Clin Oncol. 2000 Apr;18(7):1451–1457. doi: 10.1200/JCO.2000.18.7.1451. [DOI] [PubMed] [Google Scholar]
  11. Comella P., Frasci G., Panza N., Manzione L., Lorusso V., Di Rienzo G., Cioffi R., De Cataldis G., Maiorino L., Bilancia D. Cisplatin, gemcitabine, and vinorelbine combination therapy in advanced non-small-cell lung cancer: a phase II randomized study of the Southern Italy Cooperative Oncology Group. J Clin Oncol. 1999 May;17(5):1526–1534. doi: 10.1200/JCO.1999.17.5.1526. [DOI] [PubMed] [Google Scholar]
  12. Cortes J. E., Pazdur R. Docetaxel. J Clin Oncol. 1995 Oct;13(10):2643–2655. doi: 10.1200/JCO.1995.13.10.2643. [DOI] [PubMed] [Google Scholar]
  13. Crawford J., O'Rourke M., Schiller J. H., Spiridonidis C. H., Yanovich S., Ozer H., Langleben A., Hutchins L., Koletsky A., Clamon G. Randomized trial of vinorelbine compared with fluorouracil plus leucovorin in patients with stage IV non-small-cell lung cancer. J Clin Oncol. 1996 Oct;14(10):2774–2784. doi: 10.1200/JCO.1996.14.10.2774. [DOI] [PubMed] [Google Scholar]
  14. Crinò L., Scagliotti G. V., Ricci S., De Marinis F., Rinaldi M., Gridelli C., Ceribelli A., Bianco R., Marangolo M., Di Costanzo F. 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. 1999 Nov;17(11):3522–3530. doi: 10.1200/JCO.1999.17.11.3522. [DOI] [PubMed] [Google Scholar]
  15. Crook A., Duffy A., Girling D. J., Souhami R. L., Parmar M. K. Survey on the treatment of non-small cell lung cancer (NSCLC) in England and Wales. Eur Respir J. 1997 Jul;10(7):1552–1558. doi: 10.1183/09031936.97.10071552. [DOI] [PubMed] [Google Scholar]
  16. Depierre A., Chastang C., Quoix E., Lebeau B., Blanchon F., Paillot N., Lemarie E., Milleron B., Moro D., Clavier J. Vinorelbine versus vinorelbine plus cisplatin in advanced non-small cell lung cancer: a randomized trial. Ann Oncol. 1994 Jan;5(1):37–42. doi: 10.1093/oxfordjournals.annonc.a058687. [DOI] [PubMed] [Google Scholar]
  17. Fossella F. V., DeVore R., Kerr R. N., Crawford J., Natale R. R., Dunphy F., Kalman L., Miller V., Lee J. S., Moore M. Randomized phase III trial of docetaxel versus vinorelbine or ifosfamide in patients with advanced non-small-cell lung cancer previously treated with platinum-containing chemotherapy regimens. The TAX 320 Non-Small Cell Lung Cancer Study Group. J Clin Oncol. 2000 Jun;18(12):2354–2362. doi: 10.1200/JCO.2000.18.12.2354. [DOI] [PubMed] [Google Scholar]
  18. Frasci G., Lorusso V., Panza N., Comella P., Nicolella G., Bianco A., De Cataldis G., Iannelli A., Bilancia D., Belli M. Gemcitabine plus vinorelbine versus vinorelbine alone in elderly patients with advanced non-small-cell lung cancer. J Clin Oncol. 2000 Jul;18(13):2529–2536. doi: 10.1200/JCO.2000.18.13.2529. [DOI] [PubMed] [Google Scholar]
  19. Furuse K., Fukuoka M., Kuba M., Yamori S., Nakai Y., Negoro S., Katagami N., Takada Y., Kinuwaki E., Kawahara M. Randomized study of vinorelbine (VRB) versus vindesine (VDS) in previously untreated stage IIIB or IV non-small-cell lung cancer (NSCLC). The Japan Vinorelbine Lung Cancer Cooperative Study Group. Ann Oncol. 1996 Oct;7(8):815–820. doi: 10.1093/oxfordjournals.annonc.a010760. [DOI] [PubMed] [Google Scholar]
  20. Gatzemeier U., von Pawel J., Gottfried M., ten Velde G. P., Mattson K., de Marinis F., Harper P., Salvati F., Robinet G., Lucenti A. Phase III comparative study of high-dose cisplatin versus a combination of paclitaxel and cisplatin in patients with advanced non-small-cell lung cancer. J Clin Oncol. 2000 Oct 1;18(19):3390–3399. doi: 10.1200/JCO.2000.18.19.3390. [DOI] [PubMed] [Google Scholar]
  21. Giaccone G., Splinter T. A., Debruyne C., Kho G. S., Lianes P., van Zandwijk N., Pennucci M. C., Scagliotti G., van Meerbeeck J., van Hoesel Q. 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 Cancer Lung Cancer Cooperative Group. J Clin Oncol. 1998 Jun;16(6):2133–2141. doi: 10.1200/JCO.1998.16.6.2133. [DOI] [PubMed] [Google Scholar]
  22. Hardy J. R., Noble T., Smith I. E. Symptom relief with moderate dose chemotherapy (mitomycin-C, vinblastine and cisplatin) in advanced non-small cell lung cancer. Br J Cancer. 1989 Nov;60(5):764–766. doi: 10.1038/bjc.1989.355. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Jaakkimainen L., Goodwin P. J., Pater J., Warde P., Murray N., Rapp E. Counting the costs of chemotherapy in a National Cancer Institute of Canada randomized trial in nonsmall-cell lung cancer. J Clin Oncol. 1990 Aug;8(8):1301–1309. doi: 10.1200/JCO.1990.8.8.1301. [DOI] [PubMed] [Google Scholar]
  24. Jadad A. R., Moore R. A., Carroll D., Jenkinson C., Reynolds D. J., Gavaghan D. J., McQuay H. J. Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials. 1996 Feb;17(1):1–12. doi: 10.1016/0197-2456(95)00134-4. [DOI] [PubMed] [Google Scholar]
  25. Jüni P., Witschi A., Bloch R., Egger M. The hazards of scoring the quality of clinical trials for meta-analysis. JAMA. 1999 Sep 15;282(11):1054–1060. doi: 10.1001/jama.282.11.1054. [DOI] [PubMed] [Google Scholar]
  26. Kosmidis P., Mylonakis N., Dimopoulos A., Pavlidis N., Fountzilas G., Samantas E., Dimitriadis K., Kalophonos C., Tsavdaridis D., Skarlos D. Combination chemotherapy with paclitaxel plus carboplatin versus paclitaxel plus gemcitabine in inoperable non-small cell lung cancer: a phase III randomized study. Preliminary results. Hellenic Cooperative Oncology Group. Semin Oncol. 2000 Feb;27(1 Suppl 2):3–8. [PubMed] [Google Scholar]
  27. Le Chevalier T., Brisgand D., Douillard J. Y., Pujol J. L., 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. 1994 Feb;12(2):360–367. doi: 10.1200/JCO.1994.12.2.360. [DOI] [PubMed] [Google Scholar]
  28. Lipworth B. J., Aziz I. Bronchodilator response to albuterol after regular formoterol and effects of acute corticosteroid administration. Chest. 2000 Jan;117(1):156–162. doi: 10.1378/chest.117.1.156. [DOI] [PubMed] [Google Scholar]
  29. Lorusso V., Carpagnano F., Frasci G., Panza N., Di Rienzo G., Cisternino M. L., Napoli G., Orlando S., Cinieri S., Brunetti C. Phase I/II study of gemcitabine plus vinorelbine as first-line chemotherapy of non-small-cell lung cancer. J Clin Oncol. 2000 Jan;18(2):405–411. doi: 10.1200/JCO.2000.18.2.405. [DOI] [PubMed] [Google Scholar]
  30. Manegold C., Bergman B., Chemaissani A., Dornoff W., Drings P., Kellokumpu-Lehtinen P., Liippo K., Mattson K., van Pawel J., Ricci S. Single-agent gemcitabine versus cisplatin-etoposide: early results of a randomised phase II study in locally advanced or metastatic non-small-cell lung cancer. Ann Oncol. 1997 Jun;8(6):525–529. doi: 10.1023/a:1008207731111. [DOI] [PubMed] [Google Scholar]
  31. Marino P., Pampallona S., Preatoni A., Cantoni A., Invernizzi F. Chemotherapy vs supportive care in advanced non-small-cell lung cancer. Results of a meta-analysis of the literature. Chest. 1994 Sep;106(3):861–865. doi: 10.1378/chest.106.3.861. [DOI] [PubMed] [Google Scholar]
  32. Martoni A., Guaraldi M., Piana E., Strocchi E., Petralia A., Busutti L., Preti P., Robustelli G., Raimondi M., Ferrara G. Multicenter randomized clinical trial on high-dose epirubicin plus cis-platinum versus vinorelbine plus cis-platinum in advanced non small cell lung cancer. Lung Cancer. 1998 Oct;22(1):31–38. doi: 10.1016/s0169-5002(98)00065-8. [DOI] [PubMed] [Google Scholar]
  33. O'Brien M. E., Cullen M. Managing patients with lung cancer. Guidelines must help bring us in line with European standards. BMJ. 2000 Jun 10;320(7249):1604–1605. [PubMed] [Google Scholar]
  34. Perng R. P., Chen Y. M., Ming-Liu J., Tsai C. M., Lin W. C., Yang K. Y., 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. 1997 May;15(5):2097–2102. doi: 10.1200/JCO.1997.15.5.2097. [DOI] [PubMed] [Google Scholar]
  35. Perry M. C., Ihde D. C., Herndon J. E., 2nd, Grossbard M. L., Grethein S. J., Atkins J. N., Vokes E. E., Green M. R. Paclitaxel/ifosfamide or navelbine/ifosfamide chemotherapy for advanced non-small cell lung cancer: CALGB 9532. Lung Cancer. 2000 Apr;28(1):63–68. doi: 10.1016/s0169-5002(99)00129-4. [DOI] [PubMed] [Google Scholar]
  36. Postmus P. E., Giaccone G., Debruyne C., Sahmoud T., Splinter T. A., van Zandwijk N. Results of the phase II EORTC study comparing paclitaxel/cisplatin with teniposide/cisplatin in patients with non-small cell lung cancer. EORTC Lung Cancer Cooperative Group. Semin Oncol. 1996 Oct;23(5 Suppl 12):10–13. [PubMed] [Google Scholar]
  37. Pérol M., Guérin J. C., Thomas P., Poirier R., Carles P., Robinet G., Kleisbauer J. P., Paillotin D., Vergnenègre A., Balmes P. Multicenter randomized trial comparing cisplatin-mitomycin-vinorelbine versus cisplatin-mitomycin-vindesine in advanced non-small cell lung cancer. 'Groupe Français de Pneumo-Cancérologie'. Lung Cancer. 1996 Feb;14(1):119–134. doi: 10.1016/0169-5002(95)00517-x. [DOI] [PubMed] [Google Scholar]
  38. Ranson M., Davidson N., Nicolson M., Falk S., Carmichael J., Lopez P., Anderson H., Gustafson N., Jeynes A., Gallant G. Randomized trial of paclitaxel plus supportive care versus supportive care for patients with advanced non-small-cell lung cancer. J Natl Cancer Inst. 2000 Jul 5;92(13):1074–1080. doi: 10.1093/jnci/92.13.1074. [DOI] [PubMed] [Google Scholar]
  39. Roszkowski K., Pluzanska A., Krzakowski M., Smith A. P., Saigi E., Aasebo U., Parisi A., Pham Tran N., Olivares R., Berille J. A multicenter, randomized, phase III study of docetaxel plus best supportive care versus best supportive care in chemotherapy-naive patients with metastatic or non-resectable localized non-small cell lung cancer (NSCLC). Lung Cancer. 2000 Mar;27(3):145–157. doi: 10.1016/s0169-5002(00)00094-5. [DOI] [PubMed] [Google Scholar]
  40. Sandler A. B., Nemunaitis J., Denham C., von Pawel J., Cormier Y., Gatzemeier U., Mattson K., Manegold C., Palmer M. C., Gregor A. Phase III trial of gemcitabine plus cisplatin versus cisplatin alone in patients with locally advanced or metastatic non-small-cell lung cancer. J Clin Oncol. 2000 Jan;18(1):122–130. doi: 10.1200/JCO.2000.18.1.122. [DOI] [PubMed] [Google Scholar]
  41. Shepherd F. A., Dancey J., Ramlau R., Mattson K., Gralla R., O'Rourke M., Levitan N., Gressot L., Vincent M., Burkes R. Prospective randomized trial of docetaxel versus best supportive care in patients with non-small-cell lung cancer previously treated with platinum-based chemotherapy. J Clin Oncol. 2000 May;18(10):2095–2103. doi: 10.1200/JCO.2000.18.10.2095. [DOI] [PubMed] [Google Scholar]
  42. Silvestri G., Pritchard R., Welch H. G. Preferences for chemotherapy in patients with advanced non-small cell lung cancer: descriptive study based on scripted interviews. BMJ. 1998 Sep 19;317(7161):771–775. doi: 10.1136/bmj.317.7161.771. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Smith I. E. Palliative chemotherapy for advanced non-small cell lung cancer. BMJ. 1994 Feb 12;308(6926):429–430. doi: 10.1136/bmj.308.6926.429. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Smith T. J., Hillner B. E., Neighbors D. M., McSorley P. A., Le Chevalier T. Economic evaluation of a randomized clinical trial comparing vinorelbine, vinorelbine plus cisplatin, and vindesine plus cisplatin for non-small-cell lung cancer. J Clin Oncol. 1995 Sep;13(9):2166–2173. doi: 10.1200/JCO.1995.13.9.2166. [DOI] [PubMed] [Google Scholar]
  45. Souquet P. J., Chauvin F., Boissel J. P., Cellerino R., Cormier Y., Ganz P. A., Kaasa S., Pater J. L., Quoix E., Rapp E. Polychemotherapy in advanced non small cell lung cancer: a meta-analysis. Lancet. 1993 Jul 3;342(8862):19–21. doi: 10.1016/0140-6736(93)91882-m. [DOI] [PubMed] [Google Scholar]
  46. Thatcher N., Anderson H., Betticher D. C., Ranson M. Symptomatic benefit from gemcitabine and other chemotherapy in advanced non-small cell lung cancer: changes in performance status and tumour-related symptoms. Anticancer Drugs. 1995 Dec;6 (Suppl 6):39–48. doi: 10.1097/00001813-199512006-00007. [DOI] [PubMed] [Google Scholar]
  47. Waugh N., Scott D. How should different life expectancies be valued? BMJ. 1998 Apr 25;316(7140):1316–1316. doi: 10.1136/bmj.316.7140.1316. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Wozniak A. J., Crowley J. J., Balcerzak S. P., Weiss G. R., Spiridonidis C. H., Baker L. H., Albain K. S., Kelly K., Taylor S. A., Gandara D. R. Randomized trial comparing cisplatin with cisplatin plus vinorelbine in the treatment of advanced non-small-cell lung cancer: a Southwest Oncology Group study. J Clin Oncol. 1998 Jul;16(7):2459–2465. doi: 10.1200/JCO.1998.16.7.2459. [DOI] [PubMed] [Google Scholar]
  49. ten Bokkel Huinink W. W., Bergman B., Chemaissani A., Dornoff W., Drings P., Kellokumpu-Lehtinen P. L., Liippo K., Mattson K., von Pawel J., Ricci S. Single-agent gemcitabine: an active and better tolerated alternative to standard cisplatin-based chemotherapy in locally advanced or metastatic non-small cell lung cancer. Lung Cancer. 1999 Nov;26(2):85–94. doi: 10.1016/s0169-5002(99)00067-7. [DOI] [PubMed] [Google Scholar]

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