Shoichi Kuyama1, Nobuaki Ochi2, Akihiro Bessho3, Katsuyuki Hotta4, Genyo Ikeda5, Daizo Kishino6, Toshio Kubo7, Daijiro Harada8, Nobukazu Fujimoto9, Masamoto Nakanishi1, Takahiro Umeno10, Toshiaki Okada11, Kenichi Chikamori6, Tomoko Yamagishi12, Kadoaki Ohashi7, Eiki Ichihara7, Nagio Takigawa13, Mitsune Tanimoto14, Katsuyuki Kiura7. 1. Department of Respiratory Medicine, Iwakuni Clinical Center, Iwakuni, Japan. 2. Department of General Internal Medicine 4, Kawasaki Medical School, Okayama, Japan. 3. Department of Respiratory Medicine, Japanese Red Cross Okayama Hospital, Okayama, Japan. 4. Center for Innovative Clinical Medicine, Okayama University Hospital, Okayama, Japan. 5. Department of Respiratory Medicine, Chugoku Central Hospital, Fukuyama, Japan. 6. Department of Medical Oncology, Yamaguchi-Ube Medical Center, Ube, Japan. 7. Department of Allergy and Respiratory Medicine, Okayama University Hospital, Okayama, Japan. 8. Department of Thoracic Oncology and Medicine, Shikoku Cancer Center, Matsuyama, Japan. 9. Department of Medical Oncology, Okayama Rosai Hospital, Okayama, Japan. 10. Department of Respiratory Medicine, Iwakuni Clinical Center, Iwakuni, Japan; Department of Respiratory Medicine, Japanese Red Cross Okayama Hospital, Okayama, Japan. 11. Department of Respiratory Medicine, Chugoku Central Hospital, Fukuyama, Japan; Department of Respiratory Medicine, Fukuyama Medical Center, Fukuyama, Japan. 12. Department of General Internal Medicine 4, Kawasaki Medical School, Okayama, Japan; Department of Medical Oncology, Okayama Rosai Hospital, Okayama, Japan. 13. Department of General Internal Medicine 4, Kawasaki Medical School, Okayama, Japan. Electronic address: ntakigaw@gmail.com. 14. Department of Respiratory Medicine, Iwakuni Clinical Center, Iwakuni, Japan; Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan.
Abstract
INTRODUCTION: S-1 is an oral fluoropyrimidine-based combination of tegafur, gimeracil, and oteracil potassium. Although the combination of S-1 with carboplatin is a first-line chemotherapy regimen for advanced non-small cell lung cancer (NSCLC), the efficacy and safety of the regimen in the elderly remain unknown. METHODS: The patient inclusion criteria were previously untreated advanced NSCLC, wild-type epidermal growth factor receptor, aged 70 years or more, and a performance status (PS) of 0-2. The patients received oral S-1 (40mg/m2, twice daily) for 2 weeks and carboplatin (area under the curve: 5) on day 1 every 4 weeks as induction treatment. After four induction cycles, S-1 alone (40mg/m2, twice daily) was administered for 2 weeks every 4 weeks as a maintenance therapy until disease progression. The primary endpoint was the overall response rate (ORR), which was expected to exceed 20%, and the secondary endpoints included the disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and the toxicity profile. The associations between clinical outcomes and expression of genes such as thymidylate synthase and thymidine phosphorylase in the tumors were evaluated. RESULTS: Thirty-three patients were enrolled between March 2013 and June 2015. The median age was 78 (range 70-89) years, and 51.5% had a PS of 0. The ORR was 30.3% (95% confidence interval (CI): 14.6-46.0) and the DCR 57.6% (95% CI: 40.7-74.4). Grade 3/4 toxicities included thrombocytopenia (42.4%), neutropenia (33.3%), and anemia (27.3%). There was one treatment-related death due to aspiration pneumonia following febrile neutropenia. The median PFS and OS were 134days (95% CI: 79-173) and 479days (95% CI: 250-571), respectively. Low thymidine phosphorylase expression was associated with the DCR (P<0.01). CONCLUSION: This study met the predesigned primary endpoint, and the regimen seems to be a favorable treatment option.
INTRODUCTION:S-1 is an oral fluoropyrimidine-based combination of tegafur, gimeracil, and oteracil potassium. Although the combination of S-1 with carboplatin is a first-line chemotherapy regimen for advanced non-small cell lung cancer (NSCLC), the efficacy and safety of the regimen in the elderly remain unknown. METHODS: The patient inclusion criteria were previously untreated advanced NSCLC, wild-type epidermal growth factor receptor, aged 70 years or more, and a performance status (PS) of 0-2. The patients received oral S-1 (40mg/m2, twice daily) for 2 weeks and carboplatin (area under the curve: 5) on day 1 every 4 weeks as induction treatment. After four induction cycles, S-1 alone (40mg/m2, twice daily) was administered for 2 weeks every 4 weeks as a maintenance therapy until disease progression. The primary endpoint was the overall response rate (ORR), which was expected to exceed 20%, and the secondary endpoints included the disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and the toxicity profile. The associations between clinical outcomes and expression of genes such as thymidylate synthase and thymidine phosphorylase in the tumors were evaluated. RESULTS: Thirty-three patients were enrolled between March 2013 and June 2015. The median age was 78 (range 70-89) years, and 51.5% had a PS of 0. The ORR was 30.3% (95% confidence interval (CI): 14.6-46.0) and the DCR 57.6% (95% CI: 40.7-74.4). Grade 3/4 toxicities included thrombocytopenia (42.4%), neutropenia (33.3%), and anemia (27.3%). There was one treatment-related death due to aspiration pneumonia following febrile neutropenia. The median PFS and OS were 134days (95% CI: 79-173) and 479days (95% CI: 250-571), respectively. Low thymidine phosphorylase expression was associated with the DCR (P<0.01). CONCLUSION: This study met the predesigned primary endpoint, and the regimen seems to be a favorable treatment option.