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© 2002 American Society for Clinical Oncology
Treatment of Newly Diagnosed Glioblastoma MultiformeTechnical University Munich, Munich, Germany To the Editor:Treatment of glioblastoma multiforme (GBM) has been among the most challenging fields in oncology for more than 20 years. Despite considerable effort and notable advances in the surgical, radiotherapeutic, and chemotherapeutic fields, the trend toward continuous improvement in outcome that could be observed for many other neoplasms seemed to be almost completely absent. Patients’ prognoses are mainly determined by several tumor- and patient-related factors, whereas changes in treatment protocols so far have contributed little to avoid death from uncontrolled local disease.1 Since the 1970s, many cytotoxic drugs, most often nitrosoureas, have been added to surgery and radiotherapy for newly diagnosed high-grade glioma. However, none has unequivocally prolonged tumor control or patient survival. A meta-analysis of 16 randomized clinical trials from a 17-year period suggested a moderate increase of survival of 8.6% at 2 years by adding chemotherapy.2 Median survival increased from 9.4 to 12 months. The Medical Research Council recently published the results of a randomized study in which 674 patients were treated with surgery plus radiotherapy or additional procarbazine, lomustine, and vincristine.3 There was no statistically significant difference in median survival (9.5 v 10 months). Further statistical interpretation excluded a survival benefit of more than 7% to 8% at 2 years. Such results were not convincing enough to make chemotherapy a generally accepted part of standard first-line treatment on both sides of the Atlantic Ocean, especially for GBM and/or unselected groups of patients with high-grade glioma. In the light of these data, two phase II studies published in the March 1, 2002, issue of the Journal of Clinical Oncology merit further comment. Their most important features are summarized in Table 1. The study by Reardon et al4 included 33 patients with newly diagnosed glioma treated with surgical resection plus antitenascin monoclonal antibodies. One month later, radiotherapy was given (6 weeks, dose not specified, 88% of all patients). Afterward, 91% of the patients received 1 year of systemic alkylator-based chemotherapy. The study by Stupp et al5 included 64 patients with newly diagnosed GBM treated with radiotherapy (60 Gy) plus concomitant temozolomide (75 mg/m2/d x 7 d/wk) for 6 to 7 weeks after resection or biopsy. Afterward, temozolomide was continued for six cycles of 200 mg/m2/d for 5 days every 28 days. Neither of the articles describes further treatment in case of tumor progression.
In direct comparison, both strategies seem to improve median survival to a comparable extent, considering the fact that prognostic factors were more favorable in the study by Reardon et al.4 Acute toxicity and side effects were acceptable. Detailed data on quality of life and long-term toxicity are not available yet. The ultimate impact on survival will be determined in phase III studies. Phase III data will soon become available for the temozolomide strategy. An interesting point that needs to be emphasized is that comparable results were obtained with different treatment strategies, ie, addition of systemic treatment to surgery plus radiation versus further intensification of local treatment by monoclonal antibodies delivering an average cumulative radiation dose (external beam plus labeled antibodies) to the 2-cm-thick interface resection cavity/brain of 102 Gy. From these results, it might be interesting to repeat the antibody study with addition of temozolomide instead of conventional alkylator-based chemotherapy. The study by Stupp et al5 unfortunately confirmed the unfavorable prognosis of patients with unresectable tumors. Their median survival was only 5 months and therefore not appreciably longer than after radiotherapy alone. Obviously, systemic treatment still does not provide the answer for this group of patients, while the outlook might improve for those with residual small tumor masses after resection. REFERENCES 1. Andratschke N, Grosu AL, Molls M, et al: Perspectives in the treatment of malignant gliomas in adults. Anticancer Res 21: 3541-3550, 2001[Medline] 2. Fine HA, Dear KB, Loeffler JS, et al: Meta-analysis of radiation therapy with and without adjuvant chemotherapy for malignant gliomas in adults. Cancer 71: 2585-2597, 1993[CrossRef][Medline]
3. Medical Research Council Brain Tumor Working Party: Randomized trial of procarbazine, lomustine, and vincristine in the adjuvant treatment of high-grade astrocytoma: A Medical Research Council trial. J Clin Oncol 19: 509-518, 2001
4. Reardon DA, Akabani G, Coleman RG, et al: Phase II trial of murine 131I-labeled antitenascin monoclonal antibody 81C6 administered into surgically created resection cavities of patients with newly diagnosed malignant gliomas. J Clin Oncol 20: 1389-1397, 2002
5. Stupp R, Dietrich PY, Ostermann Kraljevic S, et al: Promising survival for patients with newly diagnosed glioblastoma multiforme treated with concomitant radiation plus temozolomide followed by adjuvant temozolomide. J Clin Oncol 20: 1375-1382, 2002
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Copyright © 2002 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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