Temozolomide (TMZ) combined with cisplatin (CDDP) in patients with brain metastases from solid tumors: a Hellenic Cooperative Oncology Group (HeCOG) Phase II study.
OBJECTIVE
To evaluate the efficacy of temozolomide (TMZ) combined with cisplatin (CDDP) in terms of response rate, time to progression (TTP) and overall survival (OS), as well as the tolerability of the regimen in patients with brain metastases from solid tumors.


METHODS
Patients (n=32) with brain metastases were treated with TMZ 150 mg/m2/day (chemotherapy-pretreated) or 200 mg/m2/day (chemotherapy-naive) for 5 days, combined with CDDP 75 mg/m2 on day 1, every 28 days. Primary tumor sites included breast cancer (n=15), lung cancer (n=12) and other (n=5). Twenty-seven patients had received prior chemotherapy for extracranial disease and 17 had prior radiotherapy to the brain.


RESULTS
One patient (3.1%) with non-small cell lung cancer (NSCLC) achieved complete response. Nine patients (28.1%; six with breast cancer, two with melanoma and one with NSCLC) achieved a partial response and five patients (16%) had stable disease. Median OS was 5.5 months and median TTP 2.9 months. One patient died from septicemia/neutropenic fever. Grade III-IV toxicities included anemia (9%), leukopenia (6%), thrombocytopenia (3%), renal toxicity (3%), headache (3%), fatigue (3%), nausea (3%), vomiting (3%), and alopecia (6%).


CONCLUSIONS
TMZ combined with CDDP is an active and well-tolerated combination in patients with brain metastases from solid tumors.
Christodoulou
Christos
C
Henry Dunant Hospital, Athens, Greece. hecogiat@otenet.gr
Bafaloukos
Dimitrios
D
Linardou
Helen
H
Aravantinos
Gerassimos
G
Bamias
Aristotelis
A
Carina
Maria
M
Klouvas
George
G
Skarlos
Dimosthenis
D
D000328:Adult; D000368:Aged; D000505:Alopecia / Q000139:chemically induced; D000740:Anemia / Q000139:chemically induced; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000556:secondary*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D002945:Cisplatin / Q000008:administration & dosage; D003606:Dacarbazine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D005260:Female; D006801:Humans; D007970:Leukopenia / Q000139:chemically induced; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008545:Melanoma / Q000188:drug therapy / Q000556:secondary; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000473:pathology; D000077204:Temozolomide; D016896:Treatment Outcome
D003606:Dacarbazine; D002945:Cisplatin; D000077204:Temozolomide
Ann Oncol. 2001 Feb;12 (2):249-54
11300333
Carcinogenesis. 1989 Sep;10(9):1681-4
2766459
Neurosurg Clin N Am. 1996 Jul;7(3):337-44
8823767
Cancer. 1997 Nov 1;80(9):1746-54
9351543
J Chemother. 1995 Jun;7(3):224-9
7562019
Clin Cancer Res. 1999 Jul;5(7):1629-37
10430061
Control Clin Trials. 1989 Mar;10(1):1-10
2702835
J Clin Oncol. 1989 Jul;7(7):916-22
2544685
Cancer Res. 1982 Jun;42(6):2474-9
6280860
J Clin Oncol. 1999 Sep;17 (9):2762-71
10561351
Lung Cancer. 1998 May;20(2):85-91
9711526
Eur J Cancer. 1999 Apr;35(4):580-5
10492631
J Neurooncol. 2001 Jul;53(3):259-65
11718258
J Pharmacol Exp Ther. 2000 Aug;294(2):664-71
10900246
Clin Cancer Res. 1999 Feb;5(2):309-17
10037179
Cancer. 1999 Apr 1;85(7):1599-605
10193952
Cancer. 1996 Oct 15;78(8):1781-8
8859192
J Clin Oncol. 2000 Jan;18(1):158-66
10623706
Cancer. 1992 Feb 15;69(4):972-80
1735089
Oncology. 1996 May-Jun;53(3):210-3
8643223
Lung Cancer. 1998 May;20(2):81-4
9711525
Ann Med. 1998 Jun;30(3):296-9
9677016
Clin Cancer Res. 1997 Oct;3(10 ):1769-74
9815562