Angeregt durch einen Fall in meinem Bekanntenkreis (der Betroffene erhält dieses Medikament über einen Katheder direkt ins Zentrum seines GBM-Rezidivs) suchte ich nach Informationen über Taxol, einem Chemotherapeutikum, das bei anaplatischen Astrozytomen und rezidivierenden Glioblastomen eingesetzt wird. (Suche bei "medline": taxol AND recurrent AND glioblastoma). Ich fand einige englische Publikationen.
Quelle: J Neurooncol 2000 Mar;47(1):59-63
Titel: Phase II study of combination taxol and estramustine phosphate in the treatment of recurrent glioblastoma multiforme.
Autoren: Rosenthal MA, Gruber ML, Glass J, Nirenberg A, Finlay J, Hochster H, Muggia FM.
Department of Clinical Haematology and Medical Ontcology, Royal Melbourne Hospital, Victoria, Australia. mark.rosenthal@ludwig.edu.au
Zitat: Taxol has activity in the treatment of high grade gliomas but estramustine phosphate (EMP) has not been used in this setting. In vitro data demonstrates that EMP is cytotoxic to glioma cell lines and estramustine binding proteins are expressed by glioma cells. The combination of Taxol and EMP is reported to be active in the treatment of hormone-refractory prostate cancer and in taxane-resistant breast and ovarian cancer. We therefore performed a phase II study to assess the activity and toxicity of this combination in high grade gliomas. Taxol was given at a dose of 225 mg/m2 intravenously over three hours on day 1 and EMP was given at a dose of 900 mg/m2 orally on days 1 through 3. Cycles were repeated every three weeks. Twenty patients with recurrent glioblastoma multiforme (GBM) were enrolled: 11 male, median age 45 years. All patients received anti-epileptic medications and 17 (80%) had received prior chemotherapy. Of 18 evaluable patients, two had partial responses (11) and six had stable disease (33%) for a minimum of eight weeks. Treatment was well tolerated with grade 3 neutropenia occurring in only three patients. There were no other grade 3 or 4 toxicities. The median time to progression for the cohort was only six weeks (range 3-60+ weeks). The median overall survival was 12 weeks (range 3-60+ weeks). In conclusion, the combination of Taxol and EMP is well tolerated and has modest activity in the treatment of recurrent GBM.
Quelle: Ann Oncol 2000 Apr;11(4):409-13
Titel: A phase II study of paclitaxel in chemonaive patients with recurrent high-grade glioma.
Autoren: Postma TJ, Heimans JJ, Luykx SA, van Groeningen CJ, Beenen LF, Hoekstra OS, Taphoorn MJ, Zonnenberg BA, Klein M, Vermorken JB.
Department of Neurology, University Hospital Vrije Universiteit Amsterdam, The Netherlands. TJ.Postma@azvu.nl
Zitat: BACKGROUND: The prognosis of malignant gliomas remains poor. In recurrent disease, chemotherapy can be considered.
PATIENTS AND METHODS: In this phase II study we determined the anti-tumour efficacy of paclitaxel 200 mg/m2 in a three-hour intravenous infusion every three weeks in chemonaive patients with recurrent high-grade glioma in terms of response, survival, and quality of life.
RESULTS: In 17 patients (14 glioblastoma multiforme, 3 anaplastic astrocytoma) 69 paclitaxel cycles were administered. Partial or complete responses were not observed. Stable disease for four to six months was observed in five patients (29%). Median time to progression and median survival were two and 10 months, respectively. Toxicity due to paclitaxel was as to be expected and minor in most cases. Quality of life and mood estimates appeared rather stable over time.
CONCLUSIONS: We conclude that three-weekly 200 mg/m2 paclitaxel chemotherapy for patients with recurrent high-grade gliomas did not lead to major complications or adverse effects on quality of life and mood. However, this therapy is of only very limited value in terms of response and survival in such patients.
Quelle: Am J Clin Oncol 2000 Apr;23(2):155-9
Titel: Treatment of recurrent glioblastoma multiforme using fractionated stereotactic radiosurgery and concurrent paclitaxel.
Autoren: Lederman G, Wronski M, Arbit E, Odaimi M, Wertheim S, Lombardi E, Wrzolek M.
Department of Radiation Oncology, Staten Island University Hospital, New York 10305, USA.
Zitat: Despite the progress in neurosurgery and radiotherapy, almost all patients treated with malignant gliomas develop recurrent tumors and die of their disease. Eighty-eight patients (median age 56 years) with recurrent glioblastoma (median tumor volume 32.7 cm3) were treated with noninvasive fractionated stereotactic radiosurgery and concurrent paclitaxel used as a sensitizer. The median interval between diagnosis of primary glioblastoma and salvage radiosurgery was 7.8 months. Four weekly treatments (median dose: 6.0 Gy) were delivered after the 3-hour paclitaxel infusion (median dose: 120 mg/m2). Survival was calculated by the Kaplan-Meier method from radiosurgery treatment. Overall median survival was 7.0 months, and the 1-year and 2-year actuarial survival rates were 17% and 3.4%, respectively. When grouped by performance status, there was no difference in survival between the patients with low and high Karnofsky score. Patients with tumor volume less than 30 cm3 survived significantly longer than those with tumor greater than 30 cm3 (9.4 vs. 5.7 months, p = 0.0001). Their 1-year survival rate was 40% and 8%, respectively. Eleven patients (11%) had reoperation because of expanding mass. Stable disease was seen in 40% of patients (n = 34), and increase in radiographically detected mass was observed in 41 patients (48.8%). Although the treatment of recurrent GBM is mostly palliative, the fractionated radiosurgery offers a chance for prolonged survival, especially in patients with a smaller tumor volume.
Quelle: Semin Radiat Oncol 1999 Apr;9(2 Suppl 1):27-33
Titel: The role of paclitaxel in the treatment of primary and metastatic brain tumors.
Autoren: Glantz MJ, Chamberlain MC, Chang SM, Prados MD, Cole BF.
Department of Medicine, University of Massachusetts School of Public Health, Amherst, MA 01003-0430, USA.
Zitat: The rationale for the use of paclitaxel to treat brain tumors includes impressive activity in a wide array of chemotherapy-resistant solid tumors, in vitro and in vivo evidence of cytotoxicity against primary brain tumors, and a paucity of effective alternative agents. A review of published studies evaluating paclitaxel alone or in combination with other chemotherapeutic agents suggests that paclitaxel alone is not highly active against newly diagnosed or recurrent glioblastoma multiforme. However, additional prospective trials are warranted to evaluate the efficacy of paclitaxel plus conventional cranial irradiation or stereotactic radiosurgery. Single-agent paclitaxel appears to be active against gliomas with an oligodendroglial component and may prove useful both as a component of initial therapy and for recurrent disease. Activity against anaplastic gliomas and brain metastases also should be explored. With radiation, a weekly paclitaxel administration schedule is particularly appealing from pharmacologic, safety, and dose-intensity perspectives. In addition, the dose of paclitaxel must be increased in patients who are concurrently receiving medications that induce the P-450 drug metabolizing system. Primary and metastatic brain tumors constitute a very difficult problem in oncology. Future investigations should be directed at evaluating paclitaxel-based chemotherapy regimens in selected brain tumor types, combining paclitaxel with stereotactic radiosurgery, and determining the importance of other proposed mechanisms of action of paclitaxel (eg, inhibition of angiogenesis and tumor invasion).
