International Journal of Clinical Oncology

, Volume 24, Issue 11, pp 1367–1376 | Cite as

Impact of pathological stage and histological subtype on clinical outcome of adjuvant chemotherapy of paclitaxel plus carboplatin versus oral uracil–tegafur for non-small cell lung cancer: subanalysis of SLCG0401 trial

  • Junichi SohEmail author
  • Shinichi Toyooka
  • Norihito Okumura
  • Hiroshige Nakamura
  • Masao Nakata
  • Motohiro Yamashita
  • Junichi Sakamoto
  • Motoi Aoe
  • Katsuyuki Hotta
  • Satoshi Morita
  • Hiroshi Date
Original Article



Pathological stage (pStage) and histological subtype are strong determinants of the treatment strategy for non-small cell lung cancer (NSCLC). Setouchi Lung Cancer study Group (SLCG) recently reported the results of a multicenter trial (SLCG0401) indicating that paclitaxel plus carboplatin (CBDCA/PTX) as adjuvant chemotherapy does not yield better survival than uracil–tegafur (UFT) in NSCLC patients with pStage IB–IIIA disease, while stratified analyses considering the pStage and histological subtype have not been performed.


We reanalyzed the overall survival (OS) and relapse-free survival (RFS) in 402 patients who had been randomly assigned to receive CBDCA/PTX or UFT by multivariate analysis with adjustments for the pStage and histological subtype.


There were no significant differences in the OS or RFS between the two treatment settings either in the entire cohort (n = 402) and in some of subsets: pStage IB (n = 228), pStage II (n = 117), adenocarcinoma (AD, n = 265), and squamous cell carcinoma (SQ, n = 101). In pStage IIIA patients (n = 57), CBDCA/PTX yielded superior RFS to UFT [hazard ratio (HR) 0.44; P = 0.016]. Among the patients with non-AD and non-SQ histology (n = 36), UFT yielded both superior OS and RFS to CBDCA/PTX (HRs 0.16 and 0.23; P = 0.046 and 0.011, respectively).


There are subsets of patients in which one or the other between UFT and CBDCA/PTX is significantly more effective. Selection of adjuvant therapy for NSCLC patients needs to be made taking into consideration the pStage and histological subtype.


Non-small cell lung cancer Paclitaxel Carboplatin Uracil–tegafur Adjuvant chemotherapy 



This work is supported, in part, by a non-profit organization Epidemiological and Clinical Research Information Network (ECRIN). We thank all 40 hospitals and institutions for their participation and cooperation for enrollment of patient and data collection for the original study (SLCG0401) (alphabetical order): Aichi Cancer Center Research Institute, Ako Central Hospital, Chugoku Central Hospital, Hiroshima City Asa Citizens Hospital, Hiroshima University Hospital, Japanese Red Cross Society Himeji Medical Center, Japanese Red Cross Wakayama Medical Center, Kagawa Prefectural Central Hospital, Kagawa Rosai Hospital, Kawasaki Medical School Hospital, Kawasaki Medical School Kawasaki Hospital, Kishiwada City Hospital, Kochi Health Sciences Center, Kurashiki Central Hospital, Kurashiki Daiichi Hospital, Kure Kyosai Hospital, Kurume University Hospital, Kyoto University Hospital, Mitoyo General Hospital, Nagasaki Harbor Medical Center City Hospital, National Hospital Organization Iwakuni Clinical Center, National Hospital Organization Kure Medical Center, National Hospital Organization Kyushu Cancer Center, National Hospital Organization Matsue Medical Center, National Hospital Organization Minami-Okayama Medical Center, National Hospital Organization Nagara Medical Center, National Hospital Organization Okayama Medical Center, National Hospital Organization Shikoku Cancer Center, National Hospital Organization Yamaguchi-Ube Medical Center, Okayama Red Cross General Hospital, Okayama Saiseikai General Hospital, Okayama University Hospital, Osaka City General Hospital, Saiseikai Noe Hospital, Shimada Municipal Hospital, Shimane University Hospital, Tottori University Hospital, Toyota Kosei Hospital, Tsuyama Chuo Hospital, and Uwajima City Hospital


This study is supported in part by an operating expense of department of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University.

Compliance with ethical standards

Conflict of interest

The following authors received research grants from companies: AstraZeneca (KH), Ono Pharmaceutical (KH), Chugai Pharmaceutical (ST and KH), Boehringer-Ingelheim (ST and KH), Astellas (KH), Novartis (KH), Bristol-Myers Squibb (KH), Eli Lilly Japan (KH) and MSD (KH). The following authors received personal fees from companies: Taiho Pharmaceutical (ST, NO, KH, SM and HD), Tsumura & CO (J. Sakamoto), Takeda Pharmaceutical (J. Sakamoto), Chugai Pharmaceutical (J. Sakamoto and KH), AstraZeneca (KH), Ono Pharmaceutical (KH), Boehringer-Ingelheim (KH), Nihon Kayaku (KH and J. Sakamoto), Novartis (KH), Bristol-Myers Squibb (KH and SM), Eli Lilly Japan (KH) and MSD (KH). All the other authors declared no conflicts of interest regarding this study.

Supplementary material

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  1. 1.
    Siegel RL, Miller KD, Jemal A (2018) Cancer statistics, 2018. CA Cancer J Clin 68:7–30CrossRefGoogle Scholar
  2. 2.
    Toyooka S, Okumura N, Nakamura H et al (2018) A multicenter randomized controlled study of paclitaxel plus carboplatin versus oral uracil-tegafur as the adjuvant chemotherapy in resected non-small cell lung cancer. J Thorac Oncol 13:699–706CrossRefGoogle Scholar
  3. 3.
    Group NM-AC, Arriagada R, Auperin A et al. (2010) Adjuvant chemotherapy, with or without postoperative radiotherapy, in operable non-small-cell lung cancer: two meta-analyses of individual patient data. Lancet 375:1267–1277.CrossRefGoogle Scholar
  4. 4.
    Keicho N, Saijo N, Shinkai T et al (1986) Phase II study of UFT in patients with advanced non-small cell lung cancer. Jpn J Clin Oncol 16:143–146CrossRefGoogle Scholar
  5. 5.
    Schiller JH, Harrington D, Belani CP et al (2002) Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer. N Engl J Med 346:92–98CrossRefGoogle Scholar
  6. 6.
    Suehisa H, Toyooka S (2009) Adjuvant chemotherapy for completely resected non-small-cell lung cancer. Acta Med Okayama 63:223–230PubMedGoogle Scholar
  7. 7.
    Postmus PE, Kerr KM, Oudkerk M et al (2017) Early and locally advanced non-small-cell lung cancer (NSCLC): ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol 28:1–21CrossRefGoogle Scholar
  8. 8.
    Wada H, Hitomi S, Teramatsu T (1996) Adjuvant chemotherapy after complete resection in non-small-cell lung cancer. West Japan study group for lung cancer surgery. J Clin Oncol 14:1048–1054CrossRefGoogle Scholar
  9. 9.
    Kato H, Ichinose Y, Ohta M et al (2004) A randomized trial of adjuvant chemotherapy with uracil–tegafur for adenocarcinoma of the lung. N Engl J Med 350:1713–1721CrossRefGoogle Scholar
  10. 10.
    Hamada C, Tsuboi M, Ohta M et al (2009) Effect of postoperative adjuvant chemotherapy with tegafur-uracil on survival in patients with stage IA non-small cell lung cancer: an exploratory analysis from a meta-analysis of six randomized controlled trials. J Thorac Oncol 4:1511–1516CrossRefGoogle Scholar
  11. 11.
    Novello S, Barlesi F, Califano R et al (2016) Metastatic non-small-cell lung cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol 27:v1–v27CrossRefGoogle Scholar
  12. 12.
    Sobin LH, Wittekind C (2002) TNM classification of malignant tumors, 6thed. Wiley, New YorkGoogle Scholar
  13. 13.
    Sobin LH, Gospodarowicz MK, Wittekind C (2010) International union against Cancer. TNM classification of malignant tumours, Wiley-Blackwell, HobokenGoogle Scholar
  14. 14.
    Hamada C, Tanaka F, Ohta M et al (2005) Meta-analysis of postoperative adjuvant chemotherapy with tegafur-uracil in non-small-cell lung cancer. J Clin Oncol 23:4999–5006CrossRefGoogle Scholar
  15. 15.
    Ebi M, Shimura T, Yamada S et al (2012) A patient with gastric adenosquamous carcinoma with intraperitoneal free cancer cells who remained recurrence-free with postoperative S-1 chemotherapy. Intern Med 51:3125–3129CrossRefGoogle Scholar
  16. 16.
    Saso K, Murata M, Asai K, et al (2015) [A case of pancreatic cancer with multiple liver metastases that developed postoperatively and showed a complete response with S-1 monotherapy]. Gan Kagaku Ryoho 42:1620–1622Google Scholar
  17. 17.
    Komatsu Y, Hama M, Shinagawa Y, et al (2012) [A case of pulmonary pleomorphic carcinoma treated with S-1 following radiotherapy]. Gan To Kagaku Ryoho 39:687–689PubMedGoogle Scholar
  18. 18.
    Zhang H, Shen G, Zhang S et al (2018) Novel fluoropyrimidine-based chemotherapy for advanced well-differentiated neuroendocrine tumors: a clinical update. Expert Opin Pharmacother 19:795–807CrossRefGoogle Scholar
  19. 19.
    Paz-Ares L, Luft A, Vicente D et al (2018) Pembrolizumab plus chemotherapy for squamous non–small-cell lung cancer. New Engl J Med 379:2040–2051CrossRefGoogle Scholar
  20. 20.
    Antonia SJ, Villegas A, Daniel D et al (2018) Overall survival with durvalumab after chemoradiotherapy in stage III NSCLC. N Engl J Med 379:2342–2350CrossRefGoogle Scholar
  21. 21.
    Yan Y, Kumar AB, Finnes H et al (2018) Combining immune checkpoint inhibitors with conventional cancer therapy. Front Immunol 9:1739CrossRefGoogle Scholar
  22. 22.
    Toews ML, Bylund DB (2005) Pharmacologic principles for combination therapy. Proc Am Thorac Soc 2:282–289 (discussion 290–281)CrossRefGoogle Scholar

Copyright information

© Japan Society of Clinical Oncology 2019

Authors and Affiliations

  • Junichi Soh
    • 1
    Email author
  • Shinichi Toyooka
    • 1
  • Norihito Okumura
    • 2
  • Hiroshige Nakamura
    • 3
  • Masao Nakata
    • 4
  • Motohiro Yamashita
    • 5
  • Junichi Sakamoto
    • 6
  • Motoi Aoe
    • 7
  • Katsuyuki Hotta
    • 8
  • Satoshi Morita
    • 9
  • Hiroshi Date
    • 10
  1. 1.Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical SciencesOkayama UniversityOkayamaJapan
  2. 2.Department of Thoracic SurgeryKurashiki Central HospitalKurashikiJapan
  3. 3.Division of General Thoracic SurgeryTottori University HospitalYonagoJapan
  4. 4.Department of General Thoracic SurgeryKawasaki Medical SchoolKurashikiJapan
  5. 5.Department of Thoracic SurgeryShikoku Cancer CenterMatsuyamaJapan
  6. 6.Tokai Central HospitalKakamigaharaJapan
  7. 7.Department of SurgeryKagawa Prefectural Central HospitalTakamatsuJapan
  8. 8.Center for Innovative Clinical MedicineOkayama University HospitalOkayamaJapan
  9. 9.Department of Biomedical Statistics and BioinformaticsKyoto UniversityKyotoJapan
  10. 10.Department of Thoracic SurgeryKyoto UniversityKyotoJapan

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