title: Phase I trial of tipifarnib (R115777) concurrent with radiotherapy in patients with glioblastoma multiforme.
abstract: OBJECTIVE
  To conduct a Phase I trial to determine the maximally tolerated dose (MTD) of tipifarnib in combination with conventional three-dimensional conformal radiotherapy (RT) for patients with glioblastoma multiforme.
  
  
  METHODS
  After resection or biopsy, tipifarnib was given 1 week before and then continuously during RT (60 Gy), followed by adjuvant administration until progression. The tipifarnib dose during RT was escalated in cohorts of 3 starting at 200 mg/day.
  
  
  RESULTS
  Thirteen patients were enrolled, and 12 were evaluable for MTD. Of these patients, 7 had undergone biopsy, 4 had partial resection, and 1 had gross total resection. No dose-limiting toxicity (DLT) was observed during the concomitant treatment at 200 mg. All 3 patients at 300 mg experienced DLT during the concomitant treatment: 1 with sudden death and 2 with acute pneumonitis. The MTD was reached at 300 mg. The adjuvant treatment was suppressed from the protocol after a case of pneumonitis during this treatment. Six additional patients were included at 200 mg/day of the new protocol, confirming the safety of this treatment. Of the 9 evaluable patients, 1 had partial response, 4 had stable disease, and 3 had rapid progression; the patient with gross total resection was relapse-free after 21 months. Median survival of the evaluable patients was 12 months (range, 5.2-21 months).
  
  
  CONCLUSIONS
  Tipifarnib (200 mg/day) concurrent with standard radiotherapy is well tolerated in patients with glioblastoma. Preliminary efficacy results are encouraging.
authors.affiliation: Department of Radiation Oncology, Institut Claudius Regaud, Toulouse, France. moyal.elizabeth@claudiusregaud.fr
authors.forename: Elizabeth Cohen-Jonathan
authors.initials: EC
authors.lastname: Moyal
authors.forename: Anne
authors.initials: A
authors.lastname: Laprie
authors.forename: Martine
authors.initials: M
authors.lastname: Delannes
authors.forename: Muriel
authors.initials: M
authors.lastname: Poublanc
authors.forename: Isabelle
authors.initials: I
authors.lastname: Catalaa
authors.forename: Florence
authors.initials: F
authors.lastname: Dalenc
authors.forename: Delphine
authors.initials: D
authors.lastname: Berchery
authors.forename: Jean
authors.initials: J
authors.lastname: Sabatier
authors.forename: Philippe
authors.initials: P
authors.lastname: Bousquet
authors.forename: Peter
authors.initials: P
authors.lastname: De Porre
authors.forename: Béatrice
authors.initials: B
authors.lastname: Alaux
authors.forename: Christine
authors.initials: C
authors.lastname: Toulas
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy* / Q000601:surgery; D003131:Combined Modality Therapy; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy* / Q000532:radiotherapy* / Q000601:surgery; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D015363:Quinolones / Q000009:adverse effects / Q000627:therapeutic use*; D017564:Radiation Pneumonitis / Q000209:etiology; D011879:Radiotherapy Dosage; D020266:Radiotherapy, Conformal / Q000009:adverse effects
chemical_list: D000970:Antineoplastic Agents; D015363:Quinolones; C402769:tipifarnib