Feasibility of adjuvant chemotherapy with S-1 plus carboplatin followed by single-agent maintenance therapy with S-1 for completely resected non-small-cell lung cancer: results of the Setouchi Lung Cancer Group Study 1001
This multicenter study evaluated the feasibility of novel adjuvant chemotherapy with S-1 plus carboplatin followed by single-agent, long-term maintenance with S-1 in patients with completely resected stage II–IIIA non-small-cell lung cancer (NSCLC).
Patients received four cycles of S-1 (80 mg/m2/day for 2 weeks, followed by 2 weeks rest) plus carboplatin (area under the curve 5, day 1) followed by S-1 (80 mg/m2/day for 2 weeks, followed by a 1-week rest). Patients unable to continue S-1 plus carboplatin because of severe toxicity converted to single-agent S-1 maintenance. The duration of adjuvant chemotherapy was 10 months in both situations. The primary endpoint was feasibility, defined as the proportion of patients who completed four cycles of S-1 plus carboplatin and single-agent S-1 maintenance for 10 months. The treatment completion rate was determined; treatment was considered feasible if the lower 90% confidence interval (CI) was ≥50%.
Eighty-nine patients were enrolled, of whom 87 were eligible and assessable. Seventy-eight patients (89.7%) completed four cycles of S-1 plus carboplatin and 55 (63.2%) completed the following S-1 maintenance therapy for a total of 10 months. The treatment completion rate was 63.2% (90% CI, 54.4–71.2%), indicating feasibility. There were no treatment-related deaths. Grade 3/4 toxicities included neutropenia (13.8%), thrombocytopenia (11.5%), and anorexia (4.6%). The 2-year relapse-free survival rate was 59.8%.
We concluded that adjuvant chemotherapy with S-1 plus carboplatin followed by single-agent maintenance therapy with S-1 is feasible and tolerable in patients with completely resected NSCLC.
Clinical registration number
KeywordsNon-small-cell lung cancer Adjuvant chemotherapy S-1 Carboplatin Maintenance therapy
This work was supported, in part, by a non-profit organization, Epidemiological and Clinical Research Information Network (ECRIN). We are indebted to Ms. Yumi Miyashita (ECRIN) for data management, and Dr. Hideyuki Nishi (Okayama Rousai Hospital), Dr. Minoru Fukuda (Japanese Red Cross Nagasaki Genbaku Hospital), Dr. Shingo Harita (Chugoku Central Hospital of the Mutual Aid Association of Public School Teachers), Dr. Yoshifumi Sano (Ehime University Hospital), Dr. Masayoshi Teramachi (Osaka Saiseikai Noe Hospital), Dr. Shinji Kosaka (Shimane Prefectural Central Hospital), Dr. Takuji Fujinaga (Nagara Medical Center), Dr. Ryo Miyahara (Kyoto City Hospital), Dr. Eiji Miyahara (Saiseikai Hiroshima Hospital), Dr. Hidetoshi Inokawa (Mitoyo General Hospital), and Dr. Shinsuke Kajiwara (Uwajima City Hospital) for their contributions to this study.
Compliance with ethical standards
Conflict of interest
N.O., S.T., K.H., H.Y., and H.D. received honoraria from Taiho Pharmaceutical in Japan. All other authors declared no conflicts of interest regarding this study.
- 2.Douillard JY, Rosell R, De Lena M et al (2006) 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 randomized controlled trial. Lancet Oncol 7:719–727CrossRefPubMedGoogle Scholar
- 6.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 4:1511–1516CrossRefPubMedGoogle Scholar
- 13.Okamoto I, Yoshioka H, Morita S et al (2010) Phase III trial comparing oral S-1 plus carboplatin with paclitaxel plus carboplatin in chemotherapy-naïve patients with advanced non-small-cell lung cancer: results of a West Japan Oncology Group study. J Clin Oncol 28:5240–5246CrossRefPubMedGoogle Scholar
- 16.Paz-Ares L, de Marinis F, Dediu M et al (2012) Maintenance therapy with pemetrexed plus best supportive care versus placebo plus best supportive care after induction therapy with pemetrexed plus cisplatin for advanced non-squamous non-small-cell lung cancer (PARAMOUNT): a double-blind, phase 3, randomised controlled trial. Lancet Oncol 13:247–255CrossRefPubMedGoogle Scholar
- 17.Sobin LH, Gospodarowicz MK, Wittekind C (2009) TNM classification of malignant tumours, 7th edn. Wiley-Blackwell, HobokenGoogle Scholar
- 19.Ettinger DS, Berger MJ, Armstrong DK et al (2015) Title of subordinate document. In: NCCN Version 2.2014, Antiemesis. National Comprehensive Cancer Network. http://www.nccn.org/professionals/physician_gls/pdf/antiemesis.pdf. Accessed Mar 2015
- 25.Niho S, Ikeda N, Michimae H et al (2013) Feasibility trial for adjuvant chemotherapy with docetaxel plus cisplatin followed by single agent long-term administration of S-1 chemotherapy in patients with completely resected non-small cell lung cancer: Thoracic Oncology Research Group study 0809. Br J Cancer 378:1–7Google Scholar