title: A phase I dose-escalation study (ISIDE-BT-1) of accelerated IMRT with temozolomide in patients with glioblastoma.
abstract: OBJECTIVE
  To determine the maximum tolerated dose (MTD) of fractionated intensity-modulated radiotherapy (IMRT) with temozolomide (TMZ) in patients with glioblastoma.
  
  
  METHODS
  A Phase I clinical trial was performed. Eligible patients had surgically resected or biopsy-proven glioblastoma. Patients started TMZ (75 mg/day) during IMRT and continued for 1 year (150-200 mg/day, Days 1-5 every 28 days) or until disease progression. Clinical target volume 1 (CTV1) was the tumor bed +/- enhancing lesion with a 10-mm margin; CTV2 was the area of perifocal edema with a 20-mm margin. Planning target volume 1 (PTV1) and PTV2 were defined as the corresponding CTV plus a 5-mm margin. IMRT was delivered in 25 fractions over 5 weeks. Only the dose for PTV1 was escalated (planned dose escalation: 60 Gy, 62.5 Gy, 65 Gy) while maintaining the dose for PTV2 (45 Gy, 1.8 Gy/fraction). Dose limiting toxicities (DLT) were defined as any treatment-related nonhematological adverse effects rated as Grade >or=3 or any hematological toxicity rated as >or=4 by Radiation Therapy Oncology Group (RTOG) criteria.
  
  
  RESULTS
  Nineteen consecutive glioblastoma were treated with step-and-shoot IMRT, planned with the inverse approach (dose to the PTV1: 7 patients, 60 Gy; 6 patients, 62.5 Gy; 6 patients, 65 Gy). Five coplanar beams were used to cover at least 95% of the target volume with the 95% isodose line. Median follow-up time was 23 months (range, 8-40 months). No patient experienced DLT. Grade 1-2 treatment-related neurologic and skin toxicity were common (11 and 19 patients, respectively). No Grade >2 late neurologic toxicities were noted.
  
  
  CONCLUSIONS
  Accelerated IMRT to a dose of 65 Gy in 25 fractions is well tolerated with TMZ at a daily dose of 75 mg.
authors.affiliation: Department of Radiotherapy, John Paul II Center for High Technology Research and Education in Biomedical Sciences, Catholic University, Campobasso, Italy.
authors.forename: Alessio G
authors.initials: AG
authors.lastname: Morganti
authors.forename: Mario
authors.initials: M
authors.lastname: Balducci
authors.forename: Maurizio
authors.initials: M
authors.lastname: Salvati
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Esposito
authors.forename: Pantaleo
authors.initials: P
authors.lastname: Romanelli
authors.forename: Marica
authors.initials: M
authors.lastname: Ferro
authors.forename: Franco
authors.initials: F
authors.lastname: Calista
authors.forename: Cinzia
authors.initials: C
authors.lastname: Digesù
authors.forename: Gabriella
authors.initials: G
authors.lastname: Macchia
authors.forename: Massimo
authors.initials: M
authors.lastname: Ianiri
authors.forename: Francesco
authors.initials: F
authors.lastname: Deodato
authors.forename: Savino
authors.initials: S
authors.lastname: Cilla
authors.forename: Angelo
authors.initials: A
authors.lastname: Piermattei
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Valentini
authors.forename: Numa
authors.initials: N
authors.lastname: Cellini
authors.forename: Gian Paolo
authors.initials: GP
authors.lastname: Cantore
mesh_terms: D000328:Adult; D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage* / Q000009:adverse effects; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D003606:Dacarbazine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D019583:Dose Fractionation, Radiation; D004334:Drug Administration Schedule; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D011446:Prospective Studies; D050397:Radiotherapy, Intensity-Modulated / Q000379:methods*; D000077204:Temozolomide; D047368:Tumor Burden
chemical_list: D018906:Antineoplastic Agents, Alkylating; D003606:Dacarbazine; D000077204:Temozolomide