Phase 2 trial of temozolomide using protracted low-dose and whole-brain radiotherapy for nonsmall cell lung cancer and breast cancer patients with brain metastases.
BACKGROUND
Temozolomide (TMZ), an oral methylating imidazotetrazinone, has antitumor activity against gliomas, malignant melanomas, and brain metastasis and is presently administered as a 5-day oral schedule every 4 weeks.


METHODS
A single-institution phase 2 clinical trial was conducted to determine the efficacy and the safety profile of a new regimen based on a dose-intensified, protracted course of TMZ after whole-brain radiotherapy (WBRT). Patients were eligible if they had at least 1 bidimensionally measurable brain metastasis from breast cancer and nonsmall cell lung cancer (NSCLC). Twenty-seven patients were treated with 30 grays (Gy) of WBRT with concomitant TMZ (75 mg/m(2)/day) for 10 days, and subsequent TMZ at a dose of 75 mg/m(2) per day for 21 days every 4 weeks, for up to 12 cycles.


RESULTS
Two complete responses (7.4%) and 11 partial responses (40.7%) were achieved. The schedule appeared to be well tolerated, with grade 3 toxicity (graded according to National Cancer Institute Common Toxicity Criteria) observed in only 2 patients. The overall median survival was 8.8 months and the median progression-free survival was 6 months.


CONCLUSIONS
The concomitant use of WBRT and protracted low-dose TMZ appears to be an active, well-tolerated regimen. The observed antitumor activity suggests the need for further investigation of this schedule in combination with other anticancer agents for the concomitant treatment of brain metastases and primary cancers.
Addeo
Raffaele
R
Oncology Unit, S. Giovanni di Dio Hospital, Naples, Italy. lelloaddeo@alice.it
De Rosa
Carmine
C
Faiola
Vincenzo
V
Leo
Luigi
L
Cennamo
Gregorio
G
Montella
Liliana
L
Guarrasi
Rosario
R
Vincenzi
Bruno
B
Caraglia
Michele
M
Del Prete
Salvatore
S
D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use*; D001853:Bone Marrow / Q000187:drug effects / Q000528:radiation effects; D001932:Brain Neoplasms / Q000188:drug therapy / Q000532:radiotherapy / Q000556:secondary / Q000628:therapy*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy / Q000628:therapy*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000532:radiotherapy / Q000556:secondary / Q000628:therapy*; D003131:Combined Modality Therapy; D016371:Cranial Irradiation; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy / Q000532:radiotherapy / Q000556:secondary / Q000628:therapy; D008175:Lung Neoplasms / Q000188:drug therapy / Q000532:radiotherapy / Q000556:secondary / Q000628:therapy; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012074:Remission Induction; D015996:Survival Rate; D000077204:Temozolomide
D018906:Antineoplastic Agents, Alkylating; D003606:Dacarbazine; D000077204:Temozolomide