title: A phase I study of etanidazole and radiotherapy in malignant glioma.
abstract: OBJECTIVE
  To determine the maximum tolerable total dose (MTD) of etanidazole (ETA) when administered with external beam radiotherapy (XRT) and as a continuous infusion during stereotactic brachytherapy for patients with malignant glioma (anaplastic astrocytoma or glioblastoma multiforme or mixed cell tumors).
  
  
  METHODS
  Seventy previously untreated patients were entered in a Phase I study. Prior to initiation of treatment, patients were stratified according to whether or not they were candidates for interstitial implantation. The implant patients (IMP, n = 17 pt) received accelerated fractionation XRT 20 Gy BID (6 h apart) to 40 Gy in 2 weeks with ETA 2 gm/m2 x 6 doses, a 2 week break and then interstitial implant to 50 Gy (4-7 days) with a continuous infusion of ETA over 90-96 h. The two sequentially conducted nonimplant arms started with accelerated fractionation XRT 2 Gy BID (6 h apart) to 40 Gy in 2 weeks with ETA 2 gm/m2 x 4-5 doses/week. NonIMP 1 arm (n = 38) received a 2-week break before standard fractionated boost XRT of 20 Gy/day for 2 weeks to a total dose of 60 Gy with ETA. NonIMP 2 arm (n = 14) did not have the 2-week break. All patients had plasma pharmacokinetic monitoring of ETA.
  
  
  RESULTS
  The dose-limiting toxicity (DLT) in the IMP group was the cramping/arthralgia syndrome (4) and the cumulative MTD was 26 gm/m2. For both nonIMP 1 and 2 the DLTs were peripheral neuropathy and the cramping-arthralgia syndrome. The MTD for nonIMP 1 was 34 gm/m2 and nonIMP 2, 30 gm/m2.
  
  
  CONCLUSIONS
  The clinical efficacy and radiation-related toxicity of these regimens are being evaluated. The doses of ETA that can be used with accelerated fractionation and with external beam irradiation plus brachytherapy have been established.
authors.affiliation: Joint Center for Radiation Therapy, Harvard Medical School, Boston, MA 02115.
authors.forename: N E
authors.initials: NE
authors.lastname: Riese
authors.forename: J S
authors.initials: JS
authors.lastname: Loeffler
authors.forename: P
authors.initials: P
authors.lastname: Wen
authors.forename: E
authors.initials: E
authors.lastname: Alexander
authors.forename: P M
authors.initials: PM
authors.lastname: Black
authors.forename: C N
authors.initials: CN
authors.lastname: Coleman
mesh_terms: D000328:Adult; D000368:Aged; D001918:Brachytherapy; D001932:Brain Neoplasms / Q000532:radiotherapy*; D017341:Etanidazole / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D005910:Glioma / Q000532:radiotherapy*; D006801:Humans; D008297:Male; D008875:Middle Aged
chemical_list: D017341:Etanidazole