title: Randomized phase II trial comparing amrubicin with re-challenge of platinum doublet in patients with sensitive-relapsed small-cell lung cancer: North Japan Lung Cancer Study Group trial 0702.
abstract: OBJECTIVE
  Amrubicin and re-challenge of platinum doublet are both effective treatments for sensitive-relapsed small-cell lung cancer (SCLC). However, no comparative study of these treatments has been reported. This randomized study was conducted to select the most suitable regimen for future evaluation.
  
  
  METHODS
  SCLC patients who had relapsed more than 90 days after their first-line platinum-doublet regimen were randomized to receive amrubicin (40mg/m(2), days 1-3) or re-challenge with platinum doublet. Primary endpoint was objective response rate (ORR), with secondary endpoints of progression-free survival (PFS), overall survival and toxicity profiles. We assumed that an ORR of 50% indicates potential usefulness, while that of 30% would constitute the lower limit of interest (alpha 0.1; beta 0.1). Initial estimated accrual was 28 patients to each arm.
  
  
  RESULTS
  From February 2008 to June 2013, 60 patients were enrolled and 57 patients (27 amrubicin and 30 re-challenge) were found to be evaluable for efficacy and safety. The ORR and PFS were 67% (90% confidence interval, 52-82) and 5.4 months in the amrubicin group, and 43% (90% confidence interval, 28-58) and 5.1 months in the re-challenge group, respectively. Although grade 3 febrile neutropenia was observed in 19% of patients in the amrubicin group, these episodes were transient and manageable. Non-hematological toxicities were generally moderate and no treatment-related death was observed in either group.
  
  
  CONCLUSIONS
  Only amrubicin met the primary endpoint. Moreover, amrubicin demonstrated superior efficacy over re-challenge of platinum with acceptable levels of toxicity. Further evaluation of amrubicin for sensitive-relapsed SCLC is warranted.
authors.affiliation: Department of Palliative Medicine, Tohoku University School of Medicine, 1-1, Seiryocho, Aobaku, Sendai 980-8574, Japan. Electronic address: akinoue@idac.tohoku.ac.jp.
authors.forename: Akira
authors.initials: A
authors.lastname: Inoue
authors.affiliation: Department of Pulmonary Medicine, Sendai Kousei Hospital, Sendai, Japan.
authors.forename: Shunichi
authors.initials: S
authors.lastname: Sugawara
authors.affiliation: Department of Respiratory Medicine, Miyagi Cancer Center, Natori, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Maemondo
authors.affiliation: Department of Respiratory Medicine, Iwate Prefectural Central Hospital, Morioka, Japan.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Mori
authors.affiliation: First Department of Medicine, Hokkaido University School of Medicine, Sapporo, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Oizumi
authors.affiliation: Department of Respiratory Medicine, Hokkaido Cancer Center, Sapporo, Japan.
authors.forename: Masao
authors.initials: M
authors.lastname: Harada
authors.affiliation: Department of Respiratory Medicine, Hirosaki University, Hirosaki, Japan.
authors.forename: Kageaki
authors.initials: K
authors.lastname: Taima
authors.affiliation: Divison of Pulmonary Medicine, Allergy, and Rheumatology, Department of Internal Medicine, Iwate Medical University School of Medicine, Morioka, Japan.
authors.forename: Naoto
authors.initials: N
authors.lastname: Morikawa
authors.affiliation: Department of Pulmonary Medicine, Fukushima Medical University Hospital, Fukushima, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Ishida
authors.affiliation: Department of Medical Oncology, Hokkaido University School of Medicine, Sapporo, Japan.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Kinoshita
authors.affiliation: Department of Respiratory Medicine, Saka General Hospital, Shiogama, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Watanabe
authors.affiliation: Department of Respiratory Medicine, Isawa Hospital, Oshu, Japan.
authors.forename: Toshiro
authors.initials: T
authors.lastname: Suzuki
authors.affiliation: Department of Thoracic Surgery, Omagari Kosei Medical Center, Daisen, Japan.
authors.forename: Taku
authors.initials: T
authors.lastname: Nakagawa
authors.affiliation: Department of Palliative Medicine, Tohoku University School of Medicine, 1-1, Seiryocho, Aobaku, Sendai 980-8574, Japan.
authors.forename: Ryota
authors.initials: R
authors.lastname: Saito
authors.affiliation: Department of Palliative Medicine, Tohoku University School of Medicine, 1-1, Seiryocho, Aobaku, Sendai 980-8574, Japan.
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Nukiwa
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018943:Anthracyclines / Q000009:adverse effects / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D016190:Carboplatin / Q000008:administration & dosage; D064146:Chemotherapy-Induced Febrile Neutropenia / Q000209:etiology; D002945:Cisplatin / Q000008:administration & dosage; D018572:Disease-Free Survival; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D006801:Humans; D000077146:Irinotecan; D007564:Japan; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D019233:Retreatment; D055752:Small Cell Lung Carcinoma / Q000188:drug therapy*; D015996:Survival Rate
chemical_list: D018943:Anthracyclines; D000970:Antineoplastic Agents; D005047:Etoposide; D000077146:Irinotecan; C055866:amrubicin; D016190:Carboplatin; D002945:Cisplatin; D002166:Camptothecin