title: Phase III double-blind randomized trial of radiation therapy for stage IIIb cervical cancer in combination with low- or high-dose Z-100: treatment with immunomodulator, more is not better.
abstract: BACKGROUND
  To evaluate the efficacy of low or high-dose immunomodulator, Z-100, in combination with radiotherapy for cervical cancer.
  
  
  METHODS
  Between 1995 and 1999, 221 patients with stage IIIb squamous cell carcinoma of the cervix were randomly assigned to treatment with Z-100 either at 0.2 microg or 40 microg in a double-blind manner in combination with radiotherapy.
  
  
  RESULTS
  The 5-year survival of patients with high-dose and low-dose Z-100 was 41.5% (95% CI: 31.7-51.3%) and 58.2% (95% CI: 48.7-67.7%), respectively, showing a 30% reduction in the death rate (hazard ratio: 0.670 [95% CI: 0.458-0.980], P = 0.039). Survival of high-dose group was equivalent to the 4-year survival of the radiotherapy plus hydroxyurea arm (49.7%) of GOG120 study, and that of low-dose group was similar to the survival of the cisplatin-based chemoradiation arm. The progression-free survival was also significantly improved in favor of low-dose group (hazard ratio: 0.667 [95% CI: 0.447-0.997], P = 0.048). The survival of low-dose group was similar to the survival of the cisplatin-based chemoradiation arms of the GOG120 study.
  
  
  CONCLUSIONS
  Unexpectedly, the survival of patients with advanced cervical cancer treated by lower dose of Z-100 in combination with radiotherapy was significantly better than those treated with higher dose Z-100, which was equivalent to the survival with radiotherapy alone. The hypothesis that lower dose of Z-100 enhances the efficacy of radiation therapy is now being tested by placebo-controlled randomized trial.
authors.affiliation: Kinki University, Japan.
authors.forename: Kiichiro
authors.initials: K
authors.lastname: Noda
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Ohashi
authors.forename: Hajime
authors.initials: H
authors.lastname: Sugimori
authors.forename: Masami
authors.initials: M
authors.lastname: Ozaki
authors.forename: Hideo
authors.initials: H
authors.lastname: Niibe
authors.forename: Sachio
authors.initials: S
authors.lastname: Ogita
authors.forename: Ichiro
authors.initials: I
authors.lastname: Kohno
authors.forename: Kazuo
authors.initials: K
authors.lastname: Hasegawa
authors.forename: Yuzo
authors.initials: Y
authors.lastname: Kikuchi
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Takegawa
authors.forename: Shingo
authors.initials: S
authors.lastname: Fujii
authors.forename: Kenichi
authors.initials: K
authors.lastname: Tanaka
authors.forename: Kazunori
authors.initials: K
authors.lastname: Ochiai
authors.forename: Midori
authors.initials: M
authors.lastname: Kita
authors.forename: Keiichi
authors.initials: K
authors.lastname: Fujiwara
mesh_terms: D000276:Adjuvants, Immunologic / Q000009:adverse effects / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D004306:Dose-Response Relationship, Immunologic; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008055:Lipids / Q000009:adverse effects / Q000627:therapeutic use*; D008351:Mannans / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged; D009367:Neoplasm Staging; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*
chemical_list: D000276:Adjuvants, Immunologic; D000970:Antineoplastic Agents; D008055:Lipids; D008351:Mannans; C031208:specific substance maruyama