Abstract
Purpose: 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.
Patients and methods: Patients (n=32) with brain metastases were treated with TMZ 150 mg/m2/day (chemotherapy-pretreated) or 200 mg/m2/day (chemotherapy-naïve) for 5 days, combined with CDDP 75 mg/m2on 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.
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References
Johnson JD, Young B: Demographics of brain metastasis. Neurosurg Clin N Am 337–344, 1997
R Ellis A Gregor (1998) ArticleTitleThe treatment of brain metastases from lung cancer Lung Cancer 20 81–84
K Kelly PAJ Bunn (1998) ArticleTitleIs it time to reevaluate our approach to the treatment of brain metastases in patients with non-small cell lung cancer Lung Cancer 20 85–91
M Wronski E Arbit B McCormick (1997) ArticleTitleSurgical treatment of 70 patients with brain metastases from breast carcinoma Cancer 80 1746–1754 Occurrence Handle10.1002/(SICI)1097-0142(19971101)80:9<1746::AID-CNCR8>3.0.CO;2-C Occurrence Handle1:STN:280:DyaK1c%2FhtF2jug%3D%3D Occurrence Handle9351543
S Lentzch P Reichardt F Weber V Budach B Dorken (1999) ArticleTitleBrain metastases in breast cancer prognostic factors and management Eur J Cancer 35 580–585
CM Balch GW Milton (1985) Diagnosis of metastatic melanoma at distant sites CM Balch GW Milton (Eds) Cutaneous Melanoma Lippincott JB Philadelphia, PA 221
ES Nussbaum HR Djalilian KH Cho WA Hall (1996) ArticleTitleBrain metastases. Histology, multiplicity, surgery, and survival. Cancer 78 1781–1788
JT Sundstrom H Minn KK Lertola E Nordman (1998) ArticleTitlePrognosis of patients treated for intracranial metastases with whole-brain irradiation Ann Med 30 296–299
DJ Stewart M Leavens M Maor L Feun M Luna J Bonura R Caprioli TL Loo RS Benjamin (1982) ArticleTitleHuman central nervous system distribution of cis-diamminedichloroplatinum and use as a radiosensitizer in malignant brain tumors Cancer Res 42 2474–2479
E Raymond E Izbicka H Soda SL Gerson M Dugan DD Von Hoff (1997) ArticleTitleActivity of temozolomide against human tumor colony-forming units Clin Cancer Res 3 1769–1774
R Stupp S Ostermann S Leyvraz (2001) ArticleTitleCerebrospinal fluid levels of temozolomide as a surrogate marker for brain penetration. Proc Am Soc Clin Oncol 20 59a
SD Baker M Wirth P Statkevich P Reidenberg K Alton SE Sartorius M Dugan D Culter V Batra LB Grochow RC Donehower EK Rowinsky (1999) ArticleTitleAbsorption, metabolism, and excretion of 14C-temozolomide following oral administration to patients with advanced cancer Clin Cancer Res 5 309–317
WK Yung MD Prados R Yaya-Tur SS Rosenfeld M Brada HS Friedman R Albright J Olson SM Chang AM O’Neil AH Friedman J Bruyer VA Levin (1999) ArticleTitleMulticenter phase II trial of temozolomide in patients with anaplastic astrocytoma or anaplastic oligoastrocytoma at first relapse Temodal Brain Tumor Group. J Clin Oncol 17 2762–2771
MR Middleton JJ Grob N Aaronson G Fierlbeck W Zilgen S Seiter M Gore S Aamdal J Cebon A Coates B Dreno M Henz D Schadendorf A Kapp J Weiss U Fraass P Statkevich M Muller N Thatcher (2000) ArticleTitleRandomized phase III study of temozolomide versus dacarbazine in the treatment of patients with advanced metastatic malignant melanoma J Clin Oncol 18 158–166 Occurrence Handle1:CAS:528:DC%2BD3cXmtFSqsQ%3D%3D Occurrence Handle10623706
C Christodoulou D Bafaloukos P Kosmidis E Samantas A Bamias P Papakostas A Karabelis C Bacoyiannis DV Skarlos (2001) ArticleTitlePhase II study of temozolomide in heavily pretreated cancer patients with brain metastases Ann Oncol 12 249–254
LE Abrey JD Olson JJ Raiser M Mack A Rodavitch DY Boutros MG Malkin (2001) ArticleTitleA phase II trial of temozolomide for patients with recurrent or progressive brain metastases J. Neuro-Oncol. 53 259–265
LG Wang RB Setlow (1989) ArticleTitleInactivation of O6-alkylguanine-DNA alkytransferase in HeLa cells by cisplatin Carcinogenesis 10 1681–1684
S D’Atri G Graziani PM Lacal V Nistico S Gilberti I Faraoni AJ Watson E Bonmasaar GP Margison (2000) ArticleTitleAttenuation of O (6)-methylguanine-DNA methyltransferase activity and mRNA levels by cisplatin and temozolomide in jurkat cells J Pharmacol Exp Ther 294 664–671
D Piccioni S D’Atri G Papa T Caravita A Franchi E Bonmassar G Graziani (1995) ArticleTitleCisplatin increases sensitivity of human leukemic blasts to triazine compounds J Chemother 7 224–229
CD Britten EK Rowinsky SD Baker SS Agarwalla JR Eckardt R Barrington SG Diab LA Hammond T Johnson M Villanova-Calero U Fraass P Statkevich DD Von Hoff SG Eckhardt (1999) ArticleTitleA phase I and pharmacokinetic study of temozolomide and cisplatin in patients with advanced solid malignancies Clin Cancer Res 5 1629–1637
World Health Organization: WHO Handbook for Reporting Results of Cancer Treatment. WHO Offset Publication No. 48. WHO, Geneva, 1979.
R Simon (1989) ArticleTitleOptimal two-stage designs for phase II clinical trials Controlled Clin Trials 10 1–10
E Kaplan P Meier (1958) ArticleTitleNonparametric estimation from incomplete observations J Am Stat Assoc 53 45–481
JS Lee WK Murphy BS Glisson HM Dhingra PY Holoye WK Hong (1989) ArticleTitlePrimary chemotherapy of brain metastasis in small-cell lung cancer J Clin Oncol 7 916–922
W Boogerd O Dalesio EM Bais JJ Sande Particlevan der (1992) ArticleTitleResponse of brain metastases from breast cancer to systemic chemotherapy Cancer 69 972–980
P Malacarne A Santini A Maestri (1996) ArticleTitleResponse of brain metastases from lung cancer to systemic chemotherapy with carboplatin and etoposide Oncology 53 210–213
V Franciosi G Cocconi M Michiara F Di Costanzo V Fosser M Zonato P Carlini C Boni S Di Sarra (1999) ArticleTitleFront-line chemotherapy with cisplatin and etoposide for patients with brain metastases from breast carcinoma, non-small-cell lung carcinoma, or malignant melanoma: A prospective study Cancer 85 1599–1605
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This work has been presented in part at the 27th Congress of European Society for Medical Oncology, Nice, October 2002.
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Christodoulou, C., Bafaloukos, D., Linardou, H. et al. Temozolomide (TMZ) combined with cisplatin (CDDP) in patients with brain metastases from solid tumors: a Hellenic Cooperative Oncology Group (HeCOG) Phase II study. J Neurooncol 71, 61–65 (2005). https://doi.org/10.1007/s11060-004-9176-0
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DOI: https://doi.org/10.1007/s11060-004-9176-0