A first feasibility study of temozolomide for Japanese patients with recurrent anaplastic astrocytoma and glioblastoma multiforme.
BACKGROUND
The efficacy of temozolomide has been evaluated in phase I and phase II trials in patients with recurrent malignant gliomas in the United States and the European Union. We report a feasibility study of the palliative efficacy of temozolomide for patients with recurrent anaplastic astrocytoma (AA) and glioblastoma multiforme (GBM).


METHODS
Sixteen patients with at least two prior chemotherapy regimens were enrolled in the study. Nine patients were confirmed to have GBM and 7 patients were confirmed to have AA at the latest pathology review, and all had a Karnofsky performance status (KPS) of over 50%. The median age was 57 years (range, 31-65 years).


RESULTS
No cumulative toxicity was observed at any dose level when temozolomide was administered on a once-daily, 5-day schedule. Myelosuppression occurred, with the nadir being mid-late in the cycle (day 14 or 21). National Cancer Institute common toxicity criteria (NCI-CTC) grade 3 or 4 hematological toxicity did not occur. In the 9 GBM patients, the overall response rate (complete response + partial response [CR + PR]) was 0%. The median time to progression (TTP) was 3.5 months, and the rates of progression-free survival (PFS) at 6 and 12 months were 40% and 0%. In the 7 AA patients, the overall response rate (CR + PR) was 29% and median TTP was 9 months, while PFS rates at 6 and 12 months were 80% and 30%.


CONCLUSIONS
The favorable safety profile and the efficacy of temozolomide in Japanese patients are not incompatible with the results seen with patients in the United States and the European Union.
Aoki
Tomokazu
T
Department of Neurosurgery, Kitano Hospital, 2-4-20 Ohgimachi, Kita-ku, 530-8480, Osaka, Japan. tomokazu@kitano-hp.or.jp
Mizutani
Tomohiko
T
Ishikawa
Masatsune
M
Sugiyama
Kazuhiko
K
Hashimoto
Nobuo
N
D000328:Adult; D018906:Antineoplastic Agents, Alkylating / Q000009:adverse effects / Q000627:therapeutic use*; D001254:Astrocytoma / Q000188:drug therapy* / Q000401:mortality; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000401:mortality; D003606:Dacarbazine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D005240:Feasibility Studies; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy* / Q000401:mortality; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D010166:Palliative Care; D015996:Survival Rate; D000077204:Temozolomide
D018906:Antineoplastic Agents, Alkylating; D003606:Dacarbazine; D000077204:Temozolomide