Hirotsugu Kenmotsu1, Seiji Niho2, Takeo Ito3, Yuichi Ishikawa4, Masayuki Noguchi5, Hirohito Tada6, Ikuo Sekine7, Shun-Ichi Watanabe8, Masahiro Yoshimura9, Nobuyuki Yamamoto10, Fumihiro Oshita11, Kaoru Kubota12, Kanji Nagai13. 1. Division of Thoracic Oncology, Shizuoka Cancer Center, Shizuoka, Japan. Electronic address: h.kenmotsu@scchr.jp. 2. Division of Thoracic Oncology, National Cancer Center Hospital East, Chiba, Japan. 3. Division of Pulmonary Medicine, Kuroki Memorial Hospital, Oita, Japan. 4. Division of Pathology, Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, Japan. 5. Department of Pathology, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan. 6. Department of General Thoracic Surgery, Osaka City General Hospital, Osaka, Japan. 7. Department of Medical Oncology, Graduate School of Medicine, Chiba University, Chiba, Japan. 8. Division of Thoracic Surgery, National Cancer Center Hospital, Tokyo, Japan. 9. Division of Thoracic Surgery, Hyogo Cancer Center, Hyogo, Japan. 10. Division of Thoracic Oncology, Shizuoka Cancer Center, Shizuoka, Japan. 11. Department of Thoracic Oncology, Kanagawa Cancer Center, Yokohama, Japan. 12. Medical Oncology Division, Nippon Medical School Hospital Cancer Center, Tokyo, Japan. 13. Division of Thoracic Surgery, National Cancer Center Hospital East, Chiba, Japan.
Abstract
BACKGROUND: Large cell neuroendocrine carcinoma (LCNEC) and small cell lung cancer (SCLC) are recognized as high-grade neuroendocrine carcinomas (HGNEC) of the lung. In patients with completely resected HGNEC, platinum-based adjuvant chemotherapy may be considered. However, the optimum chemotherapy regimen has not been determined. We conducted a multicenter single-arm phase II trial to evaluate irinotecan and cisplatin in postoperative adjuvant chemotherapy for HGNEC patients. PATIENTS AND METHODS: Patients with completely resected stage I-IIIA HGNEC received four cycles of irinotecan (60 mg/m(2), day 1, 8, 15) plus cisplatin (60 mg/m(2), day 1). This regimen was repeated every 4 weeks. The primary endpoint was the rate of completion of chemotherapy (defined as having undergone three or four cycles), and secondary endpoints were the rate of 3-year relapse-free survival (RFS), rate of 3-year survival and toxicities. RESULTS: Forty patients were enrolled between September 2007 and April 2010. Patients' characteristics were: median age (range) 65 [45-73] years; male 85%; ECOG-PS 1 60%; LCNEC 57% and SCLC 43%; stage IA/IB/IIB/IIIA 32/35/8/5%; 95% received lobectomy. The rate of completion of chemotherapy was 83% (90%C.I.; 71-90%). The rate of overall survival at 3 years was estimated at 81%, and that of RFS at 3 years was 74%. The rates of overall survival and RFS at 3 years were 86 and 74% among 23 LCNEC patients, and 74 and 76% among 17 SCLC patients, respectively. Nineteen patients (48%) experienced grade 3 or 4 neutropenia, but only five patients (13%) developed febrile neutropenia. Two patients (5%) developed grade 3 diarrhea, and four patients (10%) had grade 3 nausea. No treatment-related deaths were observed in this study. All 40 specimens were also diagnosed as HGNEC by central pathological review. CONCLUSIONS: The combination of irinotecan and cisplatin as postoperative adjuvant chemotherapy was feasible and possibly efficacious for resected HGNEC.
BACKGROUND: Large cell neuroendocrine carcinoma (LCNEC) and small cell lung cancer (SCLC) are recognized as high-grade neuroendocrine carcinomas (HGNEC) of the lung. In patients with completely resected HGNEC, platinum-based adjuvant chemotherapy may be considered. However, the optimum chemotherapy regimen has not been determined. We conducted a multicenter single-arm phase II trial to evaluate irinotecan and cisplatin in postoperative adjuvant chemotherapy for HGNEC patients. PATIENTS AND METHODS: Patients with completely resected stage I-IIIA HGNEC received four cycles of irinotecan (60 mg/m(2), day 1, 8, 15) plus cisplatin (60 mg/m(2), day 1). This regimen was repeated every 4 weeks. The primary endpoint was the rate of completion of chemotherapy (defined as having undergone three or four cycles), and secondary endpoints were the rate of 3-year relapse-free survival (RFS), rate of 3-year survival and toxicities. RESULTS: Forty patients were enrolled between September 2007 and April 2010. Patients' characteristics were: median age (range) 65 [45-73] years; male 85%; ECOG-PS 1 60%; LCNEC 57% and SCLC 43%; stage IA/IB/IIB/IIIA 32/35/8/5%; 95% received lobectomy. The rate of completion of chemotherapy was 83% (90%C.I.; 71-90%). The rate of overall survival at 3 years was estimated at 81%, and that of RFS at 3 years was 74%. The rates of overall survival and RFS at 3 years were 86 and 74% among 23 LCNEC patients, and 74 and 76% among 17 SCLCpatients, respectively. Nineteen patients (48%) experienced grade 3 or 4 neutropenia, but only five patients (13%) developed febrile neutropenia. Two patients (5%) developed grade 3 diarrhea, and four patients (10%) had grade 3 nausea. No treatment-related deaths were observed in this study. All 40 specimens were also diagnosed as HGNEC by central pathological review. CONCLUSIONS: The combination of irinotecan and cisplatin as postoperative adjuvant chemotherapy was feasible and possibly efficacious for resected HGNEC.
Authors: Arsela Prelaj; Sara Elena Rebuzzi; Gabriella Del Bene; Julio Rodrigo Giròn Berrìos; Alessandra Emiliani; Lucilla De Filippis; Alessandra Anna Prete; Silvia Pecorari; Gaia Manna; Carla Ferrara; Daniele Rossini; Flavia Longo Journal: ERJ Open Res Date: 2017-03-29