Phase I trial of tipifarnib (R115777) concurrent with radiotherapy in patients with glioblastoma multiforme.
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.
Moyal
Elizabeth Cohen-Jonathan
EC
Department of Radiation Oncology, Institut Claudius Regaud, Toulouse, France. moyal.elizabeth@claudiusregaud.fr
Laprie
Anne
A
Delannes
Martine
M
Poublanc
Muriel
M
Catalaa
Isabelle
I
Dalenc
Florence
F
Berchery
Delphine
D
Sabatier
Jean
J
Bousquet
Philippe
P
De Porre
Peter
P
Alaux
Béatrice
B
Toulas
Christine
C
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
D000970:Antineoplastic Agents; D015363:Quinolones; C402769:tipifarnib