Skip to main content
SpringerLink
Log in

Non-cancer-related mortality after cisplatin-based adjuvant chemotherapy for non-small cell lung cancer: a study-level meta-analysis of 16 randomized trials

  • Review Article
  • Published:
Medical Oncology Aims and scope Submit manuscript

Abstract

Adjuvant chemotherapy is associated with increased overall survival in non-small cell lung cancer (NSCLC), but is associated with high-grade toxicity. The effect of cisplatin-based adjuvant chemotherapy on non-lung cancer-related mortality is not well investigated. We conducted a systematic review and a study-level meta-analysis of published randomized controlled trials (RCTs) in order to determine the overall risk of non-lung cancer-related mortality associated with adjuvant cisplatin-based chemotherapy in NSCLC. PubMed was searched to identify relevant studies. Eligible publications included prospective RCTs in which cisplatin-based adjuvant chemotherapy plus local therapy was compared with local therapy alone in NSCLC. Summary incidence rates, relative risks (RRs), and 95 % confidence intervals (CIs) were calculated using fixed- or random-effects models. Primary endpoint was non-lung cancer-related mortality risk (due to cardiovascular, respiratory or second malignancy deaths for example), and secondary endpoints were chemotherapy-related, second primary tumor-related, cardiovascular-related, and unknown cause mortalities. A total of 6,430 patients with NSCLC from 16 RCTs were included in the analysis. Compared with no chemotherapy, the use of cisplatin-based adjuvant chemotherapy was associated with an increased risk of non-lung cancer-related death, with an RR of 1.30 (95 % CI 1.1–1.53; P = 0.002; incidence, 9.3 vs. 7.2 %; absolute difference 2 %). Cisplatin-based adjuvant chemotherapy was also associated with a greater risk of chemotherapy-related mortality (RR 2.16, 95 % CI 1.15–4.06; P = 0.02). Second primary tumor-related mortality and cardiovascular-related mortality were similar. In this meta-analysis of RCTs in NSCLC, cisplatin-based adjuvant chemotherapy was associated with a 30 % increase in non-lung cancer-related mortality compared with local therapy alone.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Pignon JP, Tribodet H, Scagliotti GV, et al. Lung adjuvant cisplatin evaluation: a pooled analysis by the LACE collaborative group. J Clin Oncol. 2008;26(21):3552–9.

    Article  PubMed  Google Scholar 

  2. Seng SM, Liu Z, Chiu S, et al. Risk of venous thromboembolism in cancer patients treated with cisplatin: a systematic review and meta-analysis. J Clin Oncol. 2012;30(35):4416–26.

    Article  PubMed  CAS  Google Scholar 

  3. Feldman DR, Schaffer WL, Steingart RM. Late cardiovascular toxicity following chemotherapy for germ cell tumors. J Natl Compr Canc Netw. 2012;10:537.

    PubMed  CAS  Google Scholar 

  4. Travis LB, Fosså SD, Schonfeld SJ, et al. Second cancers among 40,576 testicular cancer patients: focus on long-term survivors. J Natl Cancer Inst. 2005;97:1354.

    Article  PubMed  Google Scholar 

  5. Cuffe S, Booth CM, Peng Y, et al. Adjuvant chemotherapy for non-small-cell lung cancer in the elderly: a population-based study in Ontario, Canada. J Clin Oncol. 2012;30(15):1813–21.

    Article  PubMed  Google Scholar 

  6. Pepe C, Hasan B, Winton TL, et al. Adjuvant vinorelbine and cisplatin in elderly patients: National Cancer Institute of Canada and Intergroup Study JBR.10. J Clin Oncol. 2007;25(12):1553–61.

    Article  PubMed  CAS  Google Scholar 

  7. Jadad AR, Moore RA, Carroll D, et al. Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials. 1996;17(1):1–12.

    Article  PubMed  CAS  Google Scholar 

  8. DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials. 1986;7(3):177–88.

    Article  PubMed  CAS  Google Scholar 

  9. Arriagada R, Dunant A, Pignon JP, et al. Long-term results of the international adjuvant lung cancer trial evaluating adjuvant cisplatin-based chemotherapy in resected lung cancer. J Clin Oncol. 2010;28(1):35–42.

    Article  PubMed  CAS  Google Scholar 

  10. Butts CA, Ding K, Seymour L, et al. Randomized phase III trial of vinorelbine plus cisplatin compared with observation in completely resected stage IB and II non-small-cell lung cancer: updated survival analysis of JBR-10. J Clin Oncol. 2010;28(1):29–34.

    Article  PubMed  CAS  Google Scholar 

  11. Douillard JY, Rosell R, De Lena M, et al. Adjuvant vinorelbine plus cisplatin versus observation in patients with completely resected stage IB-IIIA non-small-cell lung cancer (Adjuvant Navelbine International Trialist Association [ANITA]): a randomised controlled trial. Lancet Oncol. 2006;7(9):719–27. Erratum in: Lancet Oncol. 2006 Oct;7(10):797.

    Article  PubMed  CAS  Google Scholar 

  12. Park JH, Lee CT, Lee HW, Baek HJ, Zo JI, Shim YM. Postoperative adjuvant chemotherapy for stage I non-small cell lung cancer. Eur J Cardiothorac Surg. 2005;27(6):1086–91.

    Article  PubMed  Google Scholar 

  13. Waller D, Peake MD, Stephens RJ, et al. Chemotherapy for patients with non-small cell lung cancer: the surgical setting of the big lung trial. Eur J Cardiothorac Surg. 2004;26(1):173–82.

    Article  PubMed  CAS  Google Scholar 

  14. Tada H, Tsuchiya R, Ichinose Y, et al. A randomized trial comparing adjuvant chemotherapy versus surgery alone for completely resected pN2 non-small cell lung cancer (JCOG9304). Lung Cancer. 2004;43(2):167–73.

    Article  PubMed  Google Scholar 

  15. Scagliotti GV, Fossati R, Torri V, et al. Randomized study of adjuvant chemotherapy for completely resected stage I, II, or IIIA non-small-cell Lung cancer. J Natl Cancer Inst. 2003;95(19):1453–61.

    Article  PubMed  CAS  Google Scholar 

  16. Wada H, Miyahara R, Tanaka F, Hitomi S. Postoperative adjuvant chemotherapy with PVM (Cisplatin + Vindesine + Mitomycin C) and UFT (Uracil + Tegaful) in resected stage I-II NSCLC (non-small cell lung cancer): a randomized clinical trial. West Japan Study Group for lung cancer surgery (WJSG). Eur J Cardiothorac Surg. 1999;15(4):438–43.

    Article  PubMed  CAS  Google Scholar 

  17. Wada H, Hitomi S, Teramatsu T. Adjuvant chemotherapy after complete resection in non-small-cell lung cancer. West Japan Study Group for lung cancer surgery. J Clin Oncol. 1996;14(4):1048–54.

    PubMed  CAS  Google Scholar 

  18. The Study Group of Adjuvant Chemotherapy for Lung Cancer (Chubu, Japan). A randomized trial of postoperative adjuvant chemotherapy in non-small cell lung cancer (the second cooperative study). Eur J Surg Oncol. 1995;21(1):69–77.

    Google Scholar 

  19. Niiranen A, Niitamo-Korhonen S, Kouri M, Assendelft A, Mattson K, Pyrhönen S. Adjuvant chemotherapy after radical surgery for non-small-cell lung cancer: a randomized study. J Clin Oncol. 1992;10(12):1927–32.

    PubMed  CAS  Google Scholar 

  20. Mineo TC, Ambrogi V, Corsaro V, Roselli M. Postoperative adjuvant therapy for stage IB non-small-cell lung cancer. Eur J Cardiothorac Surg. 2001;20(2):378–84.

    Article  PubMed  CAS  Google Scholar 

  21. Nakagawa K, Tada H, Akashi A, et al. Randomised study of adjuvant chemotherapy for completely resected p-stage I-IIIA non-small cell lung cancer. Br J Cancer. 2006;95(7):817–21.

    Article  PubMed  CAS  Google Scholar 

  22. Xu G, Rong T, Lin P. Adjuvant chemotherapy following radical surgery for non-small-cell lung cancer: a randomized study on 70 patients. Chin Med J (Engl). 2000;113(7):617–20.

    CAS  Google Scholar 

  23. Feld R, Rubinstein L, Thomas PA. Adjuvant chemotherapy with cyclophosphamide, doxorubicin, and cisplatin in patients with completely resected stage I non-small cell lung cancer. An LCSG trial. Chest. 1994;106:307S–9S.

    PubMed  CAS  Google Scholar 

  24. Ohta M, Tsuchiya R, Shimoyama M, et al. Adjuvant chemotherapy for completely resected stage III non-small-cell lung cancer. Results of a randomized prospective study. The Japan clinical oncology group. J Thorac Cardiovasc Surg. 1993;106(4):703–8.

    PubMed  CAS  Google Scholar 

  25. Arriagada R, Auperin A, Burdett S, et al. Adjuvant chemotherapy, with or without postoperative radiotherapy, in operable non-small-cell lung cancer: two meta-analyses of individual patient data. Lancet. 2010;375(9722):1267–77.

    Article  PubMed  CAS  Google Scholar 

  26. Douillard JY, Rosell R, De Lena M, Riggi M, Hurteloup P, Mahe MA, Adjuvant Navelbine International Trialist Association. Impact of postoperative radiation therapy on survival in patients with complete resection and stage I, II, or IIIA non-small-cell lung cancer treated with adjuvant chemotherapy: the adjuvant Navelbine International Trialist Association (ANITA) Randomized Trial. Int J Radiat Oncol Biol Phys. 2008;72(3):695–701.

    Article  PubMed  CAS  Google Scholar 

  27. Verso M, Gussoni G, Agnelli G. Prevention of venous thromboembolism in patients with advanced lung cancer receiving chemotherapy: a combined analysis of the PROTECHT and TOPIC-2 studies. J Thromb Haemost. 2010;8(7):1649–51.

    Article  PubMed  CAS  Google Scholar 

Download references

Conflict of interest

None.

Author information

Authors and Affiliations

  1. Medical Oncology Unit, Oncology Department, Azienda Ospedaliera Treviglio, Piazzale Ospedale 1, 24047, Treviglio, BG, Italy

    Fausto Petrelli & Sandro Barni

Authors
  1. Fausto Petrelli
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sandro Barni
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Fausto Petrelli.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Petrelli, F., Barni, S. Non-cancer-related mortality after cisplatin-based adjuvant chemotherapy for non-small cell lung cancer: a study-level meta-analysis of 16 randomized trials. Med Oncol 30, 641 (2013). https://doi.org/10.1007/s12032-013-0641-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s12032-013-0641-5

Keywords

Search

Navigation