Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Clinical Trial
. 2021 Jun 1;7(6):904-909.
doi: 10.1001/jamaoncol.2021.0113.

Effect of Second-generation vs Third-generation Chemotherapy Regimens With Thoracic Radiotherapy on Unresectable Stage III Non-Small-Cell Lung Cancer: 10-Year Follow-up of a WJTOG0105 Phase 3 Randomized Clinical Trial

Yoshitaka Zenke  1 , Masahiro Tsuboi  2 , Yasutaka Chiba  3 , Kayoko Tsujino  4 , Miyako Satouchi  5 , Kenji Sawa  6 , Junichi Shimizu  7 , Haruko Daga  8 , Daichi Fujimoto  9 , Masahide Mori  10 , Takuya Aoki  11 , Toshiyuki Sawa  12 , Shota Omori  13 , Hideo Saka  14 , Yasuo Iwamoto  15 , Motoyasu Okuno  16 , Tomonori Hirashima  17 , Kosuke Kashiwabara  18 , Motoko Tachihara  19 , Nobuyuki Ymamoto  20 , Kazuhiko Nakagawa  21
Affiliations
Clinical Trial

Effect of Second-generation vs Third-generation Chemotherapy Regimens With Thoracic Radiotherapy on Unresectable Stage III Non-Small-Cell Lung Cancer: 10-Year Follow-up of a WJTOG0105 Phase 3 Randomized Clinical Trial

Yoshitaka Zenke et al. JAMA Oncol. .

Abstract

Importance: Insufficient data are available regarding the long-term outcomes and cumulative incidences of toxic effects that are associated with chemoradiotherapy (CRT) for patients with stage III non-small-cell lung cancer.

Objective: To evaluate survival and late toxic effects 10 years after patients were treated with curative CRT.

Design, setting, and participants: This multicenter, phase 3 West Japan Thoracic Oncology Group (WJTOG) 0105 randomized clinical trial was conducted between September 2001 and September 2005 in Japan. Patients with histologically or cytologically confirmed non-small-cell lung cancer with unresectable stage III disease were assessed for eligibility. Additional data were analyzed from January 2018 to December 2019.

Interventions: A total of 440 eligible patients were randomly assigned to groups as follows: A (control), 4 cycles of mitomycin/vindesine/cisplatin plus thoracic radiotherapy (TRT) of 60 Gy; B, weekly irinotecan/carboplatin for 6 weeks plus TRT of 60 Gy followed by 2 courses of irinotecan/carboplatin consolidation; or C, weekly paclitaxel/carboplatin for 6 weeks plus TRT of 60 Gy followed by 2 courses of paclitaxel/carboplatin consolidation.

Main outcomes and measures: The primary outcome was 10-year survival probability after CRT. The secondary outcome was late toxic effects that occurred more than 90 days after initiating CRT.

Results: From September 2001 to September 2005, 440 patients (group A, n = 146 [33.2%; median (range) age, 63 (31-74) years; 18 women (12.3%)]; group B, n = 147 [33.4%; median (range) age, 63 (30-75) years; 22 women (15.0%)]; group C, n = 147 [33.4%; median (range) age, 63 (38-74) years; 19 women (12.9%)]) were enrolled. The median (range) follow-up was 11.9 (7.6-13.3) years. In groups A, B, and C, median (range) overall survival times were 20.5 (17.5-26.0), 19.8 (16.7-23.5), and 22.0 (18.7-26.2) months, respectively, and 10-year survival probabilities were 13.6%, 7.5%, and 15.2%, respectively. There were no significant differences in overall survival among treatment groups. The 10-year progression-free survival probabilities were 8.5%, 6.5%, and 11.1% in groups A, B, and C, respectively. Grade 3 or 4 late toxic effect rates were 3.4% (heart, 0.7%; lung, 2.7%) in group A, and those only affecting the lung represented 3.4% and 4.1% in groups B and C, respectively. No other cases of late toxic effects (grades 3/4) were observed since the initial report.

Conclusion and relevance: In this 10-year follow-up of a phase 3 randomized clinical trial, group C achieved similar efficacy and toxic effect profiles as group A 10 years after initiating treatment. These results serve as a historical control for the long-term comparisons of outcomes of future clinical trials of CRT.

Trial registration: UMIN Clinical Trial Registry: UMIN000030811.

PubMed Disclaimer

Conflict of interest statement

Conflict of Interest Disclosures: Dr Zenke reports personal fees from Boheinger Ingelheim, Chugai, MSD, Lilly, Taiho, Bristol Myers Squibb, and Ono Phgroupaceutical; grants and personal fees from AstraZeneca and MSD; and grants from Merck outside the submitted work. Dr Tsuboi reports grants and personal fees from AstraZeneca, MSD, Bristol Myers Squibb, and Ono Phgroupaceutical; personal fees from Eli Lilly, Taiho Phgroupaceutical, ohnson & Johnson Japan, Medtronic Japan, Teijin Phgroupa, and Chugai Phgroupaceutical; and grants from Boehringer Ingelheim outside the submitted work. Dr Chiba reports personal fees from Chugai Phgroupaceutical outside the submitted work. Dr Tsujino reports personal fees from AstraZeneca and Elekta outside the submitted work. Dr Satouchi reports grants and personal fees from AstraZeneca, Chugai Phgroupaceutical, Eli Lilly Japan, Pfizer Japan, Boehringer Ingelheim, Ono Phgroupaceutical, Novartis Phgroupaceutical, MSD, and Bristol Myers Squibb; grants from Takeda, AbbVie, ROXO Oncology, EPS International, and Ignyta; and personal fees from Taiho outside the submitted work. Dr Shimizu reports personal fees from Bristol Myers Squibb K.K., Ono Phgroupaceutical, Chugai Phgroupaceutical, Novartis, AstraZeneca, Taiho Phgroupaceutical, and MSD K.K. outside the submitted work. Dr Daga reports grants and personal fees from Chigai, personal fees from MSD and Ono, and grants from Pfizer and AstraZeneca outside the submitted work. Dr Fujimoto reports personal fees from AstraZeneca KK, Ono Phgroupaceutical, Bristol Myers Squibb, Taiho Phgroupaceutical, Chugai Phgroupaceutical, MSD KK, Boehringer Ingelheim Japan, Eli Lilly Japan KK, and Novartis Phgroupa K.K. outside the submitted work. Dr Mori reports personal fees from AstraZeneca, Chugai, Boehringer Ingelheim, Taiho, Eli Lilly Japan, Novartis Phgroupa, MSD, and Ono outside the submitted work. Dr Omori reports personal fees from Chugai Phgroupaceutical, Ono Phgroupaceutical, Taiho Phgroupaceutical, MSD, and Daiichi Sankyo outside the submitted work. Dr Saka reports grants and personal fees from MSD, AstraZeneca, Chugai, Ono, Olympus, Ili Lilly Japan, Boeringer Ingerhaim Japan, Pfizer, Parexel International, and Boston Scientific; grants from Bristol Myers Squibb, Otsuka, Takeda, WJOG, Japanese Blood Product Organization, Harada, Novel Phgroupa, Celzene, and Taisho Toyama; and personal fees from Becton Dickinson Japan, AMCO, Taiho, Kyowa Hakko Kirin, Aichi Prefectural University, Kyorin, Novartis, and Fuji Film Toyama Kagaku during the conduct of the study. Dr Kashiwabara reports personal fees from AstraZeneca Japan, Chugai Phgroupaceutical, Taiho Phamaceutical, Nippon Boehringer lngelheim, Ono Phgroupaceutical, Eli Lilly and Company, and Merck Sharp & Dohme during the conduct of the study. Dr Tachihara reports grants and personal fees from AstraZeneca and personal fees from Lilly Japan, Chugai Phgroupa, Taiho Phgroupaceutical, Boehringer Ingelheim, Ono Phgroupaceutical, MSD, and Olympus outside the submitted work. Dr Yamamoto reports grants and personal fees from MSD, Pfizer, Ono, Thermo Fisher Scientific, Daiichi Sankyo, Taiho, Takeda Phgroupaceutical, Chugai, Eli Lilly Japan K.K., Boehringer-Ingelheim; personal fees from Novartis, AstraZeneca, Bristol Myers Squibb, Technologies Japan, Nippon Kayaku; and grants from Astellas Phgroupa, Shionogi, AbbVie, Kyorin Phgroupaceutical, Eisai, Terumo Corporation, Toppan Printing, and Tosoh Corporation outside the submitted work; Dr Nakagawa reports grants and personal fees from AstraZeneca K.K., Astellas Phgroupa, MSD K.K., Ono Phgroupaceutical, Nippon Boehringer Ingelheim, Novartis Phgroupa K.K., Pfizer Japan, Bristol Myers Squibb, Eli Lilly Japan K.K., Chugai Phgroupaceutical, Daiichi Sankyo, and Merck Serono during the conduct of the study, as well as personal fees from Medicus Shuppan, Publishers, Care Net, Reno, Kyorin, Roche Diagnostics K.K., Bayer Yakuhin, Medical Mobile Communications Co, 3H Clinical Trial, Nanzando, Yodosha, Nikkei Business Publications, Thermo Fisher Scientific K.K., Yomiuri Telecasting Corporation, Nippon Kayaku, and Nichi-Iko Phgroupaceutical; grants and personal fees from Takeda Phgroupaceutical, Taiho Phgroupaceutical, SymBio Phgroupaceuticals, and AbbVie; and grants from inVentiv Health Japan, Icon Japan K.K., Gritsone Oncology, Parexel International, Kissei Phgroupaceutical, EPS Corporation, Syneos Health, Pfizer R&D Japan G.K., A2 Healthcare, Quintiles Inc/IQVIA Services Japan K.K., EP-CRSU, Linical, Eisai, CMIC Shift Zero K.K., Kyowa Hakko Kirin, Bayer Yakuhin, EPS International, and Otsuka Phgroupaceutical outside the submitted work.

Figures

Figure.
Figure.. Comparison of Overall Survival (OS) and Progression-Free Survival (PFS) Among the 3 Randomly Assigned Groups
The P value represents superiority, not noninferiority. NA indicates not applicable.
See this image and copyright information in PMC

References

    1. Aupérin A, Le Péchoux C, Rolland E, et al. . Meta-analysis of concomitant versus sequential radiochemotherapy in locally advanced non–small-cell lung cancer. J Clin Oncol. 2010;28(13):2181-2190. doi:10.1200/JCO.2009.26.2543 - DOI - PubMed
    1. Curran WJ Jr, Paulus R, Langer CJ, et al. . Sequential vs. concurrent chemoradiation for stage III non-small cell lung cancer: randomized phase III trial RTOG 9410. J Natl Cancer Inst. 2011;103(19):1452-1460. doi:10.1093/jnci/djr325 - DOI - PMC - PubMed
    1. Yamamoto N, Nakagawa K, Nishimura Y, et al. . Phase III study comparing second- and third-generation regimens with concurrent thoracic radiotherapy in patients with unresectable stage III non–small-cell lung cancer: West Japan Thoracic Oncology Group WJTOG0105. J Clin Oncol. 2010;28(23):3739-3745. doi:10.1200/JCO.2009.24.5050 - DOI - PubMed
    1. Ohe Y, Ishizuka N, Tamura T, Sekine I, Nishiwaki Y, Saijo N; Japan Clinical Oncology Group . Long-term follow-up of patients with unresectable locally advanced non-small cell lung cancer treated with chemoradiotherapy: a retrospective analysis of the data from the Japan Clinical Oncology Group trials (JCOG0003A). Cancer Sci. 2003;94(8):729-734. doi:10.1111/j.1349-7006.2003.tb01510.x - DOI - PMC - PubMed
    1. Horinouchi H, Sekine I, Sumi M, et al. . Long-term results of concurrent chemoradiotherapy using cisplatin and vinorelbine for stage III non-small-cell lung cancer. Cancer Sci. 2013;104(1):93-97. doi:10.1111/cas.12028 - DOI - PMC - PubMed

Publication types

MeSH terms

Associated data