Departments of Radiation Oncology; Department of Therapeutic Innovation and Molecular Oncology, INSERM U563, Toulouse, France.
PURPOSE: 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 AND MATERIALS: 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)\. CONCLUSION: Tipifarnib (200 mg/day) concurrent with standard radiotherapy is well tolerated in patients with glioblastoma\. Preliminary efficacy results are encouraging.
PMID: 17570606 [PubMed - as supplied by publisher]
