Combined radiochemotherapy with paclitaxel in the treatment of malignant glioma.
BACKGROUND
Paclitaxel is a radiosensitizing agent that shows a synergistic effect with radiation in malignant glioma cells. A phase I/II trial was performed in order to evaluate both feasibility and outcome of combined radiochemotherapy in malignant glioma.


METHODS
56 patients were included in the trial. Paclitaxel was administered on days 1-4, 15-18 and 29-32 18 to 24 hours prior to irradiation. Radiotherapy with 60 Gy in conventional fractionation was initiated on day 2.31 patients were included in a dose-escalation trial starting with 20 mg/m2/d and increasing up to 60 mg/m2/d in 10-mg steps. Additional 25 patients were treated with 50 mg/m2/d.


RESULTS
The regimen was very well tolerated with minimal subjective impairment such as sickness or weakness. Maximal tolerable dose was 50 mg/m2/d, with neutropenia being the dose-limiting toxicity. There were four allergic reactions and five thromboembolisms; furthermore, one patient with a normal blood count died due to pneumonia. The median survival was 12 months, and significantly favorable factors were a young age, a lower tumor grade (grade 3) and a complete resection. Varying the paclitaxel dose had no influence on outcome.


CONCLUSIONS
Combined radiochemotherapy with paclitaxel in the treatment of malignant glioma was well tolerated. Maximal tolerable dose was 50 mg/m2/d. There was no increase in survival compared with results reported in the literature.
Schuck
Andreas
A
Department of Radiotherapy, University Hospital of Münster, Germany. schuck@uni-muenster.de
Müller
Stefan B
SB
Köhler
Andreas
A
Könemann
Stefan
S
Wienstroer
Marlies
M
Mosler
Christina
C
Rübe
Claudia E
CE
Wassmann
Hansdetlef
H
Willich
Normann
N
Rübe
Christian
C
D000328:Adult; D000368:Aged; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000532:radiotherapy* / Q000601:surgery; D003131:Combined Modality Therapy; D005260:Female; D005910:Glioma / Q000188:drug therapy* / Q000401:mortality / Q000532:radiotherapy* / Q000601:surgery; D006801:Humans; D008297:Male; D008875:Middle Aged; D017239:Paclitaxel / Q000627:therapeutic use*; D011446:Prospective Studies; D011829:Radiation Dosage; D011838:Radiation-Sensitizing Agents / Q000627:therapeutic use*; D016019:Survival Analysis; D013997:Time Factors
D000972:Antineoplastic Agents, Phytogenic; D011838:Radiation-Sensitizing Agents; D017239:Paclitaxel