title: A pilot study of adjuvant chemotherapy with irinotecan and cisplatin for completely resected high-grade pulmonary neuroendocrine carcinoma (large cell neuroendocrine carcinoma and small cell lung cancer).
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.
  
  
  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.
authors.affiliation: Division of Thoracic Oncology, Shizuoka Cancer Center, Shizuoka, Japan. Electronic address: h.kenmotsu@scchr.jp.
authors.forename: Hirotsugu
authors.initials: H
authors.lastname: Kenmotsu
authors.affiliation: Division of Thoracic Oncology, National Cancer Center Hospital East, Chiba, Japan.
authors.forename: Seiji
authors.initials: S
authors.lastname: Niho
authors.affiliation: Division of Pulmonary Medicine, Kuroki Memorial Hospital, Oita, Japan.
authors.forename: Takeo
authors.initials: T
authors.lastname: Ito
authors.affiliation: Division of Pathology, Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Ishikawa
authors.affiliation: Department of Pathology, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Noguchi
authors.affiliation: Department of General Thoracic Surgery, Osaka City General Hospital, Osaka, Japan.
authors.forename: Hirohito
authors.initials: H
authors.lastname: Tada
authors.affiliation: Department of Medical Oncology, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Ikuo
authors.initials: I
authors.lastname: Sekine
authors.affiliation: Division of Thoracic Surgery, National Cancer Center Hospital, Tokyo, Japan.
authors.forename: Shun-Ichi
authors.initials: S
authors.lastname: Watanabe
authors.affiliation: Division of Thoracic Surgery, Hyogo Cancer Center, Hyogo, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Yoshimura
authors.affiliation: Division of Thoracic Oncology, Shizuoka Cancer Center, Shizuoka, Japan.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Yamamoto
authors.affiliation: Department of Thoracic Oncology, Kanagawa Cancer Center, Yokohama, Japan.
authors.forename: Fumihiro
authors.initials: F
authors.lastname: Oshita
authors.affiliation: Medical Oncology Division, Nippon Medical School Hospital Cancer Center, Tokyo, Japan.
authors.forename: Kaoru
authors.initials: K
authors.lastname: Kubota
authors.affiliation: Division of Thoracic Surgery, National Cancer Center Hospital East, Chiba, Japan.
authors.forename: Kanji
authors.initials: K
authors.lastname: Nagai
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D018278:Carcinoma, Neuroendocrine / Q000188:drug therapy* / Q000401:mortality / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D000077146:Irinotecan; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000601:surgery; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D010865:Pilot Projects; D011013:Pneumonectomy; D055815:Young Adult
chemical_list: D000077146:Irinotecan; D002945:Cisplatin; D002166:Camptothecin
keywords: Adjuvant chemotherapy; High-grade neuroendocrine carcinoma; Large cell neuroendocrine carcinoma; Lung cancer; Small cell carcinoma