title: Randomized phase I study of standard-fractionated or accelerated-hyperfractionated radiotherapy with concurrent cisplatin and vindesine for unresectable non-small cell lung cancer: a report of Japan Clinical Oncology Group Study (JCOG 9601).
abstract: BACKGROUND
  We attempted dose escalation of standard-fractionated and accelerated-hyperfractionated radiotherapy combined with concurrent cisplatin and vindesine to improve local control and survival in unresectable non-small cell lung cancer.
  
  
  METHODS
  Twenty-one patients were enrolled between June 1996 and August 1997. There were 19 males and two females and their median age was 65 years (range 45-74 years). Performance status was 0 in 10 cases and 1 in 11 cases. Disease stage was IIIA in three cases and IIIB in 18 cases. The cases were randomized to a standard-fractionated arm (n = 10) or an accelerated-hyperfractionated radiotherapy arm (n = 11) with two or three cycles of concomitant cisplatin 80 mg/m(2) on day 1 and vindesine 3 mg/m(2) on days 1 and 8 every 4 weeks in both arms. Dose escalation from 60 Gy/30 fractions/6 weeks to 70 Gy/35 fractions/7 weeks was planned in the standard-fractionated radiotherapy group and from 54 Gy/36 fractions/3.6 weeks to 60 Gy/40 fractions/4 weeks and then 66 Gy/44 fractions/4.4 weeks in the accelerated-hyperfractionated radiotherapy group.
  
  
  RESULTS
  Grade 3 or 4 hematological toxicities were observed as follows: in the standard-fractionated/accelerated-hyperfractionated radiotherapy group, leukocytopenia 9/10, anemia 2/3 and thrombocytopenia 0/2. Grade 3 non-hematological toxicity consisted of esophagitis 0/3, increased serum total bilirubin 2/0 and hypoxia 0/1. Two patients died of radiation pneumonitis in the standard-fractionated radiotherapy group. Dose-limiting toxicity was observed in four of the 10 and seven of the 11 patients at initial dose level of standard-fractionated radiotherapy, 60 Gy/30 fractions/6 weeks, and of accelerated-hyperfractionated radiotherapy, 54 Gy/36 fractions/3.6 weeks, respectively. Thus, we failed to escalate the dose of radiotherapy in both arms. The overall response rate in the standard-fractionated group and the accelerated-hyperfractionated radiotherapy group was 70 and 73% and the 1-year survival rate was 70 and 64%, respectively.
  
  
  CONCLUSIONS
  We concluded that these schedules of radiotherapy with concurrent cisplatin and vindesine were unacceptable for use in patients with unresectable non-small cell lung cancer. Further modifications of the schedule for radiotherapy and evaluation of combination with new chemotherapy are warranted.
authors.affiliation: Division of Internal Medicine, National Nishigunma Hospital, Shibukawa, Gunma, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Tsuchiya
authors.forename: Y
authors.initials: Y
authors.lastname: Ohe
authors.forename: T
authors.initials: T
authors.lastname: Sugiura
authors.forename: N
authors.initials: N
authors.lastname: Fuwa
authors.forename: Y
authors.initials: Y
authors.lastname: Kitamoto
authors.forename: K
authors.initials: K
authors.lastname: Mori
authors.forename: H
authors.initials: H
authors.lastname: Kobayashi
authors.forename: K
authors.initials: K
authors.lastname: Nakata
authors.forename: T
authors.initials: T
authors.lastname: Sawa
authors.forename: K
authors.initials: K
authors.lastname: Hirai
authors.forename: T
authors.initials: T
authors.lastname: Etoh
authors.forename: H
authors.initials: H
authors.lastname: Saka
authors.forename: A
authors.initials: A
authors.lastname: Saito
authors.forename: H
authors.initials: H
authors.lastname: Fukuda
authors.forename: N
authors.initials: N
authors.lastname: Ishizuka
authors.forename: N
authors.initials: N
authors.lastname: Saijo
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality / Q000532:radiotherapy*; D002945:Cisplatin / Q000008:administration & dosage; D019583:Dose Fractionation, Radiation; D005260:Female; D006801:Humans; D007970:Leukopenia / Q000139:chemically induced; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D015996:Survival Rate; D014751:Vindesine / Q000008:administration & dosage
chemical_list: D002945:Cisplatin; D014751:Vindesine