Chemotherapy in Adult High-Grade Glioma
Abstract & Commentary
Source: Stewart LA. Lancet. 2002;359:1011-1018.
The infiltrating nature of high-grade gliomas makes complete resection of these tumors virtually impossible. Therefore, standard treatment generally consists of cytoreductive surgery followed by radiation therapy. Nevertheless, prognosis is poor with a median survival time of 9 months and only 5-10% of patients surviving at 2 years (Bleehen NM, Stenning SP. Br J Cancer. 1991;64:769-774). Randomized trials on the effect of systemic chemotherapy on survival and recurrence in adults with high-grade glioma have had inconclusive results. Therefore, the GMT group did a systematic review and meta-analysis using data from all available randomized trials that compared radiotherapy alone with radiotherapy plus chemotherapy. The main results of this paper were based on information from 12 randomized controlled trials that included more than 3000 eligible patients or 81% of patients from all known eligible randomized trials.
Overall, the results showed a significant prolongation of survival associated with chemotherapy or a 15% relative decrease in the risk of death. This effect was equivalent to an absolute increase in 1-year survival of 6% and a 2-month increase in median survival time. There was no evidence that the effect of chemotherapy differed in any group of patients defined by age, sex, histology, performance status, or extent of resection.
Commentary
Prior to this meta-analysis, despite enrollment of more than 3500 patients in randomized trials, the question of whether chemotherapy was effective in the treatment of high-grade gliomas remained unclear. Because of this uncertainty, current treatment of gliomas varies intranationally and internationally. Stewart’s systematic review provides an up-to-date summary of the average effect of chemotherapy in adults with high-grade gliomas and provides guidance for clinical practice and further research. Stewart showed, in this comprehensive review, that high-grade gliomas can respond to chemotherapy. The question remains as to whether the benefits of chemotherapy they detected are clinically worthwhile. As they point out, benefit is likely to vary with the clinical situation and the individual patient and his family’s preferences. Tolerability of treatment and quality of life, including cognitive impairment, are major issues for patients who will survive for only a short time after their treatment has concluded. Stewart cannot answer this question because few of the trials they analyzed in their meta-analysis formally measured quality of life or undertook cognitive function tests. Nevertheless, this meta-analysis indicates that with respect to the nitrosoureas, chemotherapy is fairly well tolerated and easily administered and, therefore, is of practical use for treatment of individuals who wish to extend their likely survival time if only by a modest amount. Obviously the modest benefit of treatment and the remaining uncertainty about quality of life still allows clinicians to limit treatment to surgery and radiotherapy alone in patients whose quality of life is poor and in whom prolonging survival would be a burden both to them and to their families. Nevertheless, the small but definite improvement in survival from chemotherapy should encourage the use of available agents for the treatment of high-grade gliomas and encourage further studies of new chemotherapy agents. —John J. Caronna, Vice-Chairman, Department of Neurology, Cornell University Medical Center; Professor of Clinical Neurology, New York Hospital, Associate Editor, Neurology Alert.
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