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Pegylated liposomal doxorubicin‐efficacy in patients with recurrent high‐grade glioma
Author(s) -
Hau Peter,
Fabel Klaus,
Baumgart Ulrike,
Rümmele Petra,
Grauer Oliver,
Bock Annekatrin,
Dietmaier Christopher,
Dietmaier Wolfgang,
Dietrich Jörg,
Dudel Christine,
Hübner Franz,
Jauch Tanya,
Drechsel Elisabeth,
Kleiter Ingo,
Wismeth Cäcile,
Zellner Anton,
Brawanski Alexander,
Steinbrecher Andreas,
Marienhagen Jörg,
Bogdahn Ulrich
Publication year - 2004
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.20073
Subject(s) - medicine , doxorubicin , glioma , oncology , clinical trial , clinical endpoint , chemotherapy , surgery , pharmacology , cancer research
BACKGROUND Doxorubicin exhibits high efficacy in malignant glioma cell cultures. Nonetheless, as a standard formulation, doxorubicin has not been used clinically, due to poor penetration of the blood‐brain barrier. Furthermore, doxorubicin is known to induce tumor resistance genes. To address both of these issues, the authors investigated the use of pegylated liposomal doxorubicin (Caelyx™; Essex Pharma, Munich, Germany) alone (Trial 1) and in combination with tamoxifen (Trial 2) in two sequentially performed nonrandomized prospective Phase II trials involving patients with recurrent high‐grade glioma. METHODS Twenty patients were included in each trial. Progression‐free survival at 6 months (PFS‐6) and toxicity were the primary endpoints. Expression of the tumor resistance proteins multidrug resistance protein 1 (MDR‐1) and multiple resistance protein (MRP) was evaluated by immunohistochemical methods and by sestamibi–single‐photon emission computed tomography (SPECT). RESULTS The overall response rate (including cases of disease stabilization) was 40% in both Trial 1 and Trial 2. PFS‐6 was 15%, and the median time to disease progression was 17 weeks. It is noteworthy that 40% of patients with Grade III tumors had long‐term responses, which lasted for up to 3 years. There was no significant difference between Trial 1 and Trial 2 in terms of efficacy. Both regimens were well tolerated, with the main side effect being palmoplantar erythrodysesthesia. The authors found no correlation between clinical response and expression of tumor resistance genes or between clinical response and SPECT data. CONCLUSIONS Pegylated liposomal doxorubicin administered alone or in combination with tamoxifen is safe and moderately effective in patients with recurrent high‐grade glioma. None of the putative predictors for response that were evaluated proved to be significant in this setting. Cancer 2004. © 2004 American Cancer Society.