Hirotsugu Kenmotsu1, Seiji Niho2, Masahiro Tsuboi3, Masashi Wakabayashi4, Genichiro Ishii5, Kazuo Nakagawa6, Haruko Daga7, Hiroshi Tanaka8, Haruhiro Saito9, Keiju Aokage3, Toshiaki Takahashi1, Toshi Menju10, Takashi Kasai11, Ichiro Yoshino12, Koichi Minato13, Morihito Okada14, Junko Eba4, Hisao Asamura15, Yuichiro Ohe16, Shun-Ichi Watanabe6. 1. Division of Thoracic Oncology, Shizuoka Cancer Center, Nagaizumi-cho Sunto-gun, Japan. 2. Department of Thoracic Oncology, National Cancer Center Hospital East, Kashiwa, Japan. 3. Department of Thoracic Surgery, National Cancer Center Hospital East, Kashiwa, Japan. 4. Japan Clinical Oncology Group Data Center/Operations Office, National Cancer Center Hospital, Tokyo, Japan. 5. Division of Pathology, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center Hospital East, Kashiwa, Japan. 6. Department of Thoracic Surgery, National Cancer Center Hospital, Tokyo, Japan. 7. Department of Medical Oncology, Osaka City General Hospital, Osaka, Japan. 8. Department of Internal Medicine, Niigata Cancer Center Hospital, Niigata, Japan. 9. Department of Thoracic Oncology, Kanagawa Cancer Center, Yokohama, Japan. 10. Department of Thoracic Surgery, Graduate School of Medicine, Kyoto University. 11. Division of Thoracic Oncology, Tochigi Cancer Center, Utsunomiya, Japan. 12. Department of General Thoracic Surgery, Chiba University Graduate School of Medicine, Chiba, Japan. 13. Division of Respiratory Medicine, Gunma Prefectural Cancer Center, Ota, Japan. 14. Department of Surgical Oncology, Research Institute for Radiation Biology and Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan. 15. Division of Thoracic Surgery, Keio University School of Medicine, Tokyo, Japan. 16. Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan.
Abstract
PURPOSE: To verify the superiority of irinotecan plus cisplatin over etoposide plus cisplatin as postoperative adjuvant chemotherapy for patients with pathologic stage I-IIIA, completely resected, high-grade neuroendocrine carcinoma (HGNEC) of the lung. METHODS: This was a randomized, open-label, phase III study on patients with completely resected stage I-IIIA HGNEC of the lung. They were randomly assigned to receive either etoposide (100 mg/m2, days 1-3) plus cisplatin (80 mg/m2, day 1) or irinotecan (60 mg/m2, days 1, 8, 15) plus cisplatin (60 mg/m2, day 1) up to four cycles. The primary end point was relapse-free survival (RFS) in the intention-to-treat population. This trial was registered with the Japan Registry of Clinical Trials (jRCTs031180216). RESULTS:Between April 2013 and October 2018, 221 patients were enrolled (etoposide plus cisplatinarm, 111 patients; irinotecan plus cisplatinarm, 110 patients). In the second interim analysis, early termination of the trial was recommended because of futility. At a median follow-up of 24.1 months, the 3-year RFS was 65.4% for etoposide plus cisplatin and 69.0% for irinotecan plus cisplatin, with a hazard ratio of 1.076 (95% CI, 0.666 to 1.738; one-sided log-rank P = .619). Grade 3-4 adverse events were more frequent in the etoposide plus cisplatin arm, with febrile neutropenia (20% of 109 patients v 4% of 107 patients) and neutropenia (97% v 36%) being the most common. Meanwhile, grade 3-4 anorexia (6% v 11%) and diarrhea (1% v 8%) were more frequently observed in the irinotecan plus cisplatin arm. CONCLUSION:Irinotecan plus cisplatin is not superior to etoposide plus cisplatin for improving RFS in patients with completely resected HGNEC; thus, etoposide plus cisplatin remains the standard treatment.
RCT Entities:
PURPOSE: To verify the superiority of irinotecan plus cisplatin over etoposide plus cisplatin as postoperative adjuvant chemotherapy for patients with pathologic stage I-IIIA, completely resected, high-grade neuroendocrine carcinoma (HGNEC) of the lung. METHODS: This was a randomized, open-label, phase III study on patients with completely resected stage I-IIIA HGNEC of the lung. They were randomly assigned to receive either etoposide (100 mg/m2, days 1-3) plus cisplatin (80 mg/m2, day 1) or irinotecan (60 mg/m2, days 1, 8, 15) plus cisplatin (60 mg/m2, day 1) up to four cycles. The primary end point was relapse-free survival (RFS) in the intention-to-treat population. This trial was registered with the Japan Registry of Clinical Trials (jRCTs031180216). RESULTS: Between April 2013 and October 2018, 221 patients were enrolled (etoposide plus cisplatin arm, 111 patients; irinotecan plus cisplatin arm, 110 patients). In the second interim analysis, early termination of the trial was recommended because of futility. At a median follow-up of 24.1 months, the 3-year RFS was 65.4% for etoposide plus cisplatin and 69.0% for irinotecan plus cisplatin, with a hazard ratio of 1.076 (95% CI, 0.666 to 1.738; one-sided log-rank P = .619). Grade 3-4 adverse events were more frequent in the etoposide plus cisplatin arm, with febrile neutropenia (20% of 109 patients v 4% of 107 patients) and neutropenia (97% v 36%) being the most common. Meanwhile, grade 3-4 anorexia (6% v 11%) and diarrhea (1% v 8%) were more frequently observed in the irinotecan plus cisplatin arm. CONCLUSION:Irinotecan plus cisplatin is not superior to etoposide plus cisplatin for improving RFS in patients with completely resected HGNEC; thus, etoposide plus cisplatin remains the standard treatment.