Neues zur Chemotherapie von Gliomen

Zusammenfassung

In der Chemotherapie maligner Gliome wurden neue Standards gesetzt. Eine begleitende und adjuvante Chemotherapie mit Temozolomid zusätzlich zur Bestrahlung nach Operation eines Glioblastoms verlängerte Gesamt- und progressionsfreie Überlebenszeit in einer großen prospektiven, randomisierten Phase-III-Studie. Ob eine alleinige Chemotherapie mit Temozolomid oder mit Procarbazin, CCNU und Vincristin (PCV) einer Strahlentherapie bei Erstdiagnose eines malignen oligodendroglialen Tumors vorzuziehen ist, bleibt offen. Die diesbezüglichen Ergebnisse der großen NOA-04-Studie werden erst in einigen Jahren vorliegen. Zwei große prospektive randomisierte Phase-III-Studien zeigten keine statistisch signifikante Verlängerung der Gesamtüberlebenszeit durch eine zusätzliche PCV-Chemotherapie nach Operation und Strahlentherapie eines malignen oligodendroglialen Tumors. Im Gegensatz zu niedriggradigen astrozytären Tumoren bewirkt eine Chemotherapie mit Temozolomid oder mit PCV bei einem Teil der niedriggradigen oligodendroglialen Tumoren ein Ansprechen. Klinische Studien mit so genannten small molecules werden derzeit durchgeführt. Substanzen, welche die intrazelluläre Signalkaskade von Gliomzellen, die Neoangiogenese und andere Proliferations- und invasionsassoziierte Prozesse beeinflussen, sind derzeit in der klinischen Erprobung. Ob diese Behandlungsansätze das Therapiearsenal wesentlich erweitern werden, ist zum jetzigen Zeitpunkt offen.

Abstract

Novel standards have been established regarding the chemotherapy of gliomas. Concomitant and adjuvant chemotherapy with temozolomide in addition to postoperative radiotherapy has been proven to prolong overall- and progression-free survival of glioblastoma patients in a large randomised multicenter prospective phase III-trial in comparison with postoperative radiotherapy alone. If chemotherapy alone either with procarbacine, lomustine and vincristine (PCV) or with temozolomide is equally effective or superior to radiotherapy in the initial postoperative management of malignant oligodendroglial tumors is unclear. The German NOA-04 study addressing this question is closed, however, results will not be available in the near future. Two large randomised prospective multicenter phase III trials evaluating the efficacy of an additional PCV chemotherapy after postoperative radiotherapy of malignant oligodendroglial tumours failed to show a statistically significant improvement in overall survival. In contrast to low grade astrocytic tumours, a significant proportion of low grade oligodendroglial tumours responds to chemotherapy either with temozolomide or with PCV. Clinical trials with so called small molecules are underway. Among others, substances interfering with signal transduction, with mechanisms of tumour neo-angiogenesis or with other proliferation and invasion associated mechanisms are currently evaluated in clinical trials. If these new approaches will improve therapeutic efficacy in the future, remains to be seen.

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