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Journal of Neuro-Oncology

, Volume 71, Issue 1, pp 61–65 | Cite as

Temozolomide (TMZ) combined with cisplatin (CDDP) in patients with brain metastases from solid tumors: a Hellenic Cooperative Oncology Group (HeCOG) Phase II study

  • Christos ChristodoulouEmail author
  • Dimitrios Bafaloukos
  • Helen Linardou
  • Gerassimos Aravantinos
  • Aristotelis Bamias
  • Maria Carina
  • George Klouvas
  • Dimosthenis Skarlos
Clinical Study

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.

Keywords

brain metastases breast cancer cisplatin lung cancer temozolomide 

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References

  1. Johnson JD, Young B: Demographics of brain metastasis. Neurosurg Clin N Am 337–344, 1997 Google Scholar
  2. Ellis, R, Gregor, A 1998The treatment of brain metastases from lung cancerLung Cancer208184Google Scholar
  3. Kelly, K, Bunn, PAJ 1998Is it time to reevaluate our approach to the treatment of brain metastases in patients with non-small cell lung cancerLung Cancer208591Google Scholar
  4. Wronski, M, Arbit, E, McCormick, B 1997Surgical treatment of 70 patients with brain metastases from breast carcinomaCancer8017461754CrossRefPubMedGoogle Scholar
  5. Lentzch, S, Reichardt, P, Weber, F, Budach, V, Dorken, B 1999Brain metastases in breast cancer prognostic factors and managementEur J Cancer35580585Google Scholar
  6. Balch, CM, Milton, GW 1985Diagnosis of metastatic melanoma at distant sitesBalch, CMMilton, GW eds. Cutaneous MelanomaLippincott JBPhiladelphia, PA221Google Scholar
  7. Nussbaum, ES, Djalilian, HR, Cho, KH, Hall, WA 1996Brain metastases. Histology, multiplicity, surgery, and survival.Cancer7817811788Google Scholar
  8. Sundstrom, JT, Minn, H, Lertola, KK, Nordman, E 1998Prognosis of patients treated for intracranial metastases with whole-brain irradiationAnn Med30296299Google Scholar
  9. Stewart, DJ, Leavens, M, Maor, M, Feun, L, Luna, M, Bonura, J, Caprioli, R, Loo, TL, Benjamin, RS 1982Human central nervous system distribution of cis-diamminedichloroplatinum and use as a radiosensitizer in malignant brain tumorsCancer Res4224742479Google Scholar
  10. Raymond, E, Izbicka, E, Soda, H, Gerson, SL, Dugan, M, Von Hoff, DD 1997Activity of temozolomide against human tumor colony-forming unitsClin Cancer Res317691774Google Scholar
  11. Stupp, R, Ostermann, S, Leyvraz, S 2001Cerebrospinal fluid levels of temozolomide as a surrogate marker for brain penetration.Proc Am Soc Clin Oncol2059aGoogle Scholar
  12. Baker, SD, Wirth, M, Statkevich, P, Reidenberg, P, Alton, K, Sartorius, SE, Dugan, M, Culter, D, Batra, V, Grochow, LB, Donehower, RC, Rowinsky, EK 1999Absorption, metabolism, and excretion of 14C-temozolomide following oral administration to patients with advanced cancerClin Cancer Res5309317Google Scholar
  13. Yung, WK, Prados, MD, Yaya-Tur, R, Rosenfeld, SS, Brada, M, Friedman, HS, Albright, R, Olson, J, Chang, SM, O’Neil, AM, Friedman, AH, Bruyer, J, Levin, VA 1999Multicenter phase II trial of temozolomide in patients with anaplastic astrocytoma or anaplastic oligoastrocytoma at first relapseTemodal Brain Tumor Group. J Clin Oncol1727622771Google Scholar
  14. Middleton, MR, Grob, JJ, Aaronson, N, Fierlbeck, G, Zilgen, W, Seiter, S, Gore, M, Aamdal, S, Cebon, J, Coates, A, Dreno, B, Henz, M, Schadendorf, D, Kapp, A, Weiss, J, Fraass, U, Statkevich, P, Muller, M, Thatcher, N 2000Randomized phase III study of temozolomide versus dacarbazine in the treatment of patients with advanced metastatic malignant melanomaJ Clin Oncol18158166PubMedGoogle Scholar
  15. Christodoulou, C, Bafaloukos, D, Kosmidis, P, Samantas, E, Bamias, A, Papakostas, P, Karabelis, A, Bacoyiannis, C, Skarlos, DV 2001Phase II study of temozolomide in heavily pretreated cancer patients with brain metastasesAnn Oncol12249254Google Scholar
  16. Abrey, LE, Olson, JD, Raiser, JJ, Mack, M, Rodavitch, A, Boutros, DY, Malkin, MG 2001A phase II trial of temozolomide for patients with recurrent or progressive brain metastasesJ. Neuro-Oncol.53259265Google Scholar
  17. Wang, LG, Setlow, RB 1989Inactivation of O6-alkylguanine-DNA alkytransferase in HeLa cells by cisplatinCarcinogenesis1016811684Google Scholar
  18. D’Atri, S, Graziani, G, Lacal, PM, Nistico, V, Gilberti, S, Faraoni, I, Watson, AJ, Bonmasaar, E, Margison, GP 2000Attenuation of O (6)-methylguanine-DNA methyltransferase activity and mRNA levels by cisplatin and temozolomide in jurkat cellsJ Pharmacol Exp Ther294664671Google Scholar
  19. Piccioni, D, D’Atri, S, Papa, G, Caravita, T, Franchi, A, Bonmassar, E, Graziani, G 1995Cisplatin increases sensitivity of human leukemic blasts to triazine compoundsJ Chemother7224229Google Scholar
  20. Britten, CD, Rowinsky, EK, Baker, SD, Agarwalla, SS, Eckardt, JR, Barrington, R, Diab, SG, Hammond, LA, Johnson, T, Villanova-Calero, M, Fraass, U, Statkevich, P, Von Hoff, DD, Eckhardt, SG 1999A phase I and pharmacokinetic study of temozolomide and cisplatin in patients with advanced solid malignanciesClin Cancer Res516291637Google Scholar
  21. World Health Organization: WHO Handbook for Reporting Results of Cancer Treatment. WHO Offset Publication No. 48. WHO, Geneva, 1979.Google Scholar
  22. Simon, R 1989Optimal two-stage designs for phase II clinical trialsControlled Clin Trials10110Google Scholar
  23. Kaplan, E, Meier, P 1958Nonparametric estimation from incomplete observationsJ Am Stat Assoc5345481Google Scholar
  24. Lee, JS, Murphy, WK, Glisson, BS, Dhingra, HM, Holoye, PY, Hong, WK 1989Primary chemotherapy of brain metastasis in small-cell lung cancerJ Clin Oncol7916922Google Scholar
  25. Boogerd, W, Dalesio, O, Bais, EM, Sande, JJ 1992Response of brain metastases from breast cancer to systemic chemotherapyCancer69972980Google Scholar
  26. Malacarne, P, Santini, A, Maestri, A 1996Response of brain metastases from lung cancer to systemic chemotherapy with carboplatin and etoposideOncology53210213Google Scholar
  27. Franciosi, V, Cocconi, G, Michiara, M, Di Costanzo, F, Fosser, V, Zonato, M, Carlini, P, Boni, C, Di Sarra, S 1999Front-line chemotherapy with cisplatin and etoposide for patients with brain metastases from breast carcinoma, non-small-cell lung carcinoma, or malignant melanoma: A prospective studyCancer8515991605Google Scholar

Copyright information

© Springer 2005

Authors and Affiliations

  • Christos Christodoulou
    • 1
    Email author
  • Dimitrios Bafaloukos
    • 2
  • Helen Linardou
    • 2
  • Gerassimos Aravantinos
    • 3
  • Aristotelis Bamias
    • 4
  • Maria Carina
    • 5
  • George Klouvas
    • 1
  • Dimosthenis Skarlos
    • 1
  1. 1.‘Henry Dunant’ HospitalAthensGreece
  2. 2.Metropolitan HospitalGreece
  3. 3.‘Agioi Anargiroi’ Cancer HospitalAthens
  4. 4.University of Ioannina Medical SchoolIoannina
  5. 5.Aristotle University of Thessaloniki Medical SchoolThessalonikiGreece

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