Abstract
Treosulfan is a bifunctional alkylating prodrug with activity against various solid tumors. To improve the outcome for patients with recurrent malignant glioma, we assessed the efficacy of intravenous treosulfan (6–10 g/m2 4-weekly) as salvage therapy for patients with recurrent or progressive glioblastoma (GB, n = 14) or anaplastic astrocytoma (AA, n = 2). All patients had prior involved-field radiotherapy and adjuvant nitrosourea-based chemotherapy. A total of 56 cycles were administered. Tumor responses were assessed radiologically and clinically prior to each cycle. All patients were assessable for toxicity, response and survival. There were no complete or partial responses (CR, PR). Two patients progressed after the first cycle, 14 patients had initially stable disease (SD). Median progression-free survival was 3.25 months for the GB patients. Five patients were progression-free at 6 months (30%), including the 2 AA patients. The 2 AA patients are stable at 22 months. Myelosuppression was the dose-limiting toxicity in this cohort of nitrosourea-pretreated patients. Treosulfan has modest activity in patients with recurrent malignant glioma. Further evaluation of treosulfan in chemonaive malignant glioma patients is warranted.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Wong ET, Hess KR, Gleason MJ, Jaeckle KA, Kyritsis AP, Prados MD, Levin VA, Yung WK: Outcomes and prognostic factors in recurrent glioma patients enrolled onto phase II clinical trials. J Clin Oncol 17: 2572, 1999
Yung WK, Prados MD, Yaya-Tur R, Rosenfeld SS, Brada M, Friedman HS, Albright R, Olson J, Chang SM, O'Neill AM, Friedman AH, Bruner J, Yue N, Dugan M, Zaknoen S, Levin VA: Multicenter phase II trial of temozolomide in patients with anaplastic astrocytoma or anaplastic oligoastrocytoma at first relapse. J Clin Oncol 17: 2762, 1999
Prados MD: Phase II and III trials with temozolomide, including clinical trials in patients with brain tumors. Proc Am Assoc Cancer Res (AACR) 40: 754, 1999
Feit PW, Rastrup-Andersen N, Matagne R: Studies on epoxide formation from (2S,3S)-threitol-1,4-bismethanesulfonate. The preparation and biological activity of (2S,3S)-1,2-epoxy-3,4-butanediol 4-methanesulfonate. J Med Chem 13: 1173, 1970
Gropp M, Meier W, Hepp H: Treosulfan as an effective second-line therapy in ovarian cancer. Gynecol Oncol 71: 94, 1998
Masding J, Sarkar TK, White WF, Barley VL, Chawla SL, Boesen E, Rostom AY, Menday AP: Intravenous treosulfan versus intravenous treosulfan plus cisplatinum in advanced ovarian carcinoma. Br J Obstet Gynaecol 97: 342, 1990
Reber U, Wüllner U, Trepel M, Baumgart J, Seyfried J, Klockgether T, Dichgans J, Weller M: Potentiation of treosulfan toxicity by the glutathione-depleting agent buthionine sulfoximine in human malignant glioma cells: the role of bcl-2. Biochem Pharmacol 55: 349, 1998
Wick W, Seyfried J, Stock J, Grimmel C, Baumgart J, Weller M: Glutathione depletion in malignant glioma cells: sensitization to treosulfan action in vitro and in vivo. Neuro-Oncology 2(Suppl.1): S4, 2000
Macdonald DR, Cascino TL, Schold SC, Cairncross JG: Response criteria for phase II studies of supratentorial malignant glioma. J Clin Oncol 8: 1277, 1990
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Schmidt, F., Wick, W., Herrlinger, U. et al. Treosulfan Chemotherapy for Recurrent Malignant Glioma. J Neurooncol 49, 231–234 (2000). https://doi.org/10.1023/A:1006496831144
Issue Date:
DOI: https://doi.org/10.1023/A:1006496831144