title: Phase I/II trial of sequential chemoradiotherapy using a novel hypoxic cell radiosensitizer, doranidazole (PR-350), in patients with locally advanced non-small-cell lung Cancer (WJTOG-0002).
abstract: OBJECTIVE
  This Phase I/II trial was conducted to assess the efficacy and safety of PR-350, a novel hypoxic cell radiosensitizer, when administered with thoracic radiation therapy (RT) after induction chemotherapy (CT) for locally advanced non-small-cell lung cancer (NSCLC).
  
  
  METHODS
  Two cycles of cisplatin (80 mg/m(2)) and paclitaxel (180 mg/m(2)), or carboplatin (AUC = 6) and paclitaxel (200 mg/m(2)) were given before RT of 60 Gy in 30 fractions. In the Phase I portion, the starting dosage of PR-350 was 10 daily administrations (2000 mg/m(2)) in combination with RT, and this number was increased in increments of 10 for successive groups to 30 doses.
  
  
  RESULTS
  In total, 37 patients were enrolled. In Phase I (n = 20), PR-350 could be administered 30 times with concurrent thoracic RT. Thus, in Phase II (n = 17), PR-350 was administered 30 times. The major toxicity was radiation pneumonitis, with Grade 3 or more pneumonitis noted in 6 patients (16%) including 2 with treatment-related deaths. However, no Grade 3 or more esophageal toxicity was noted, and only Grade 1 peripheral neuropathy was noted in 9 patients (24%). For all 37 patients, the median survival time (MST) and the 2-year survival rate were 15.9 months and 24%, respectively. For 18 patients receiving 21 to 30 doses of PR-350, the MST and 2-year survival rate were 20.9 months and 33%, respectively.
  
  
  CONCLUSIONS
  Thoracic RT combined with 30 daily administrations of PR-350 after induction CT was well tolerated and promising for locally advanced NSCLC.
authors.affiliation: Department of Radiation Oncology, Kinki University School of Medicine, Osaka-Sayama, Osaka, Japan. ynishi@med.kindai.ac.jp
authors.forename: Yasumasa
authors.initials: Y
authors.lastname: Nishimura
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Nakagawa
authors.forename: Koji
authors.initials: K
authors.lastname: Takeda
authors.forename: Masahiro
authors.initials: M
authors.lastname: Tanaka
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Segawa
authors.forename: Kayoko
authors.initials: K
authors.lastname: Tsujino
authors.forename: Shunichi
authors.initials: S
authors.lastname: Negoro
authors.forename: Nobukazu
authors.initials: N
authors.lastname: Fuwa
authors.forename: Toyoaki
authors.initials: T
authors.lastname: Hida
authors.forename: Masaaki
authors.initials: M
authors.lastname: Kawahara
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Katakami
authors.forename: Keiko
authors.initials: K
authors.lastname: Hirokawa
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Yamamoto
authors.forename: Masahiro
authors.initials: M
authors.lastname: Fukuoka
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Ariyoshi
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000532:radiotherapy; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy / Q000379:methods; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage*; D008175:Lung Neoplasms / Q000188:drug therapy / Q000532:radiotherapy; D008297:Male; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage; D017564:Radiation Pneumonitis / Q000209:etiology; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage*; D011879:Radiotherapy Dosage; D015996:Survival Rate
chemical_list: D007093:Imidazoles; D011838:Radiation-Sensitizing Agents; C106738:doranidazole; D016190:Carboplatin; D017239:Paclitaxel; D002945:Cisplatin