Continuous administration of daily low-dose temozolomide in pretreated patients with advanced non-small cell lung cancer: a phase II study.
OBJECTIVE
Temozolomide, a novel triazene derivative, has shown activity in vitro against lung cancer as well as against brain metastases from a variety of solid tumors including non-small cell lung cancer (NSCLC). The aim of the study was to evaluate the efficacy and safety of temozolomide in pretreated patients with NSCLC.


METHODS
Thirty-one pretreated patients (median age 60 years) with histologically confirmed NSCLC were enrolled. Sixteen (52%) patients had a performance status (ECOG) of 0-1, 12 (39%) had pretreated brain metastases and 28 (90.3%) had received >2 lines of treatment. Temozolomide was administered at a dose of 75 mg/m(2) daily for 21 days every 28 days. A total of 73 chemotherapy cycles were administered.


RESULTS
In an intention-to-treat analysis, 2 patients (6.5%; 95% CI: -2.2 to 15.1%) achieved a partial response and 3 (10%) stable disease. The median time to progression was 2.4 months, the median survival time 3.3 months and the 1-year survival rate 22.5%. There was a toxic death due to grade 4 neutropenia. Grade 3 and 4 lymphopenia occurred in 4 (13%) and 2 (6%) patients, respectively. Nonhematological toxicity was mild, consisting of grade 2-3 asthenia (n = 14 patients) and grade 3 diarrhea (n = 1 patient).


CONCLUSIONS
Prolonged low daily doses of temozolomide demonstrate minimal activity as salvage therapy in patients with advanced NSCLC. The combination of low daily doses of temozolomide with other anticancer drugs probably merits further evaluation.
Kouroussis
Charalambos
C
Department of Medical Oncology, University General Hospital of Heraklion, Heraklion, Greece.
Vamvakas
Lambros
L
Vardakis
Nikolaos
N
Kotsakis
Athanasios
A
Kalykaki
Antonia
A
Kalbakis
Kostas
K
Saridaki
Zacharenia
Z
Kentepozidis
Nikolaos
N
Giassas
Stelios
S
Georgoulias
Vassilis
V
D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D003606:Dacarbazine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D016879:Salvage Therapy; D000077204:Temozolomide; D013997:Time Factors; D016896:Treatment Outcome; D014227:Triazines / Q000737:chemistry
D000970:Antineoplastic Agents; D014227:Triazines; D003606:Dacarbazine; D000077204:Temozolomide