title: Results of a phase II trial of external beam radiation with etanidazole (SR 2508) for the treatment of locally advanced prostate cancer (RTOG Protocol 90-20).
abstract: OBJECTIVE
  RTOG Protocol 90-20 was designed to evaluate the effect of the hypoxic cell sensitizer Etanidazole (SR-2508) on locally advanced adenocarcinoma of the prostate treated with concurrent external beam irradiation.
  
  
  METHODS
  Patients with biopsy-proven adenocarcinoma of the prostate with locally advanced T2b, T3, and T4 tumors were eligible for this study. No patients with disease beyond the pelvis were eligible. Serum prostate specific antigen (PSA) was mandatory. All patients received definitive external beam irradiation using standard four-field whole pelvis treatment to 45-50 Gy, followed by a cone down with a minimum total dose to the prostate of 66 Gy at 1.8-2.0 Gy/fraction over 6.5-7.5 weeks. Etanidazole was delivered 1.8 g/m2 given 3 times a week to a total of 34.2 g/m2 or 19 doses.
  
  
  RESULTS
  Thirty-nine patients were entered onto the study. Three patients refused treatment; therefore, 36 patients were eligible for further evaluation. Median follow-up was 36.9 months from treatment end. All patients had elevated initial PSA levels, and 18 patients had PSAs of > 20 ng/ml. Tumor classification was T2, 12 patients (33.3%); T3, 22 patients (61.1%); and T4, 2 patients (5.6%). Complete clinical response, defined as PSA < 4 ng/ml and complete clinical disappearance, was attained in 17.9% of (5/28 pts) with information at 90 days and 56% of patients by 12 months following treatment. Relapse-free survival was 13% at 3 years with PSA < 4 ng/ml. There were no Grade 4 or 5 toxicities, either acute (during treatment) or in follow-up.
  
  
  CONCLUSIONS
  Results of this trial regarding PSA response and clinical disappearance of disease are similar to historical controls and do not warrant further investigation of etanidazole as was done in this trial. Drug toxicity that, in the past, has been unacceptably high with other hypoxic cell sensitizers does not appear to be a significant problem with this drug.
authors.affiliation: Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee 53226, USA. colleen_lawton@radonc.mcw.edu
authors.forename: C A
authors.initials: CA
authors.lastname: Lawton
authors.forename: C N
authors.initials: CN
authors.lastname: Coleman
authors.forename: J W
authors.initials: JW
authors.lastname: Buzydlowski
authors.forename: J D
authors.initials: JD
authors.lastname: Forman
authors.forename: V A
authors.initials: VA
authors.lastname: Marcial
authors.forename: J D
authors.initials: JD
authors.lastname: DelRowe
authors.forename: M
authors.initials: M
authors.lastname: Rotman
mesh_terms: D000230:Adenocarcinoma / Q000097:blood / Q000473:pathology / Q000532:radiotherapy*; D000368:Aged; D000369:Aged, 80 and over; D017341:Etanidazole / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000097:blood / Q000473:pathology / Q000532:radiotherapy*; D011838:Radiation-Sensitizing Agents / Q000627:therapeutic use*; D011878:Radiotherapy / Q000009:adverse effects
chemical_list: D011838:Radiation-Sensitizing Agents; D017341:Etanidazole; D017430:Prostate-Specific Antigen