Chemoradiation and adjuvant chemotherapy for glioblastoma: Why does so much therapy yield so little improvement in survival?

Abstract

Survival for patients with glioblastoma multiforme has changed little over the last 20 years despite advancements in surgical, radiotherapeutic, chemotherapeutic, and imaging technologies (7). To improve outcome, investigators have explored ways to either physically or biologically escalate the total dose of radiation. The report by Levin and co-workers (8) in this issue describes a well conceived approach to biologically enhance the effectiveness of ionizing radiation by shortening the overall treatment time from 6 to 4 weeks (2 Gy TID) and by administering a chemotherapeutic agent (carboplatin) in low dose as a sensitizer 1.75 h before each fraction of radiotherapy ( 8). This regimen was followed by up to 1 year of adjuvant procarbazine, lomustine (CCNU), and vincristine (PCV) for patients without evidence of progressive disease. This Phase II trial was designed to address many important aspects of the evolving principles of clinical radiotherapy, The duration of radiotherapy is increasingly being recognized as a critical parameter associated with success or failure of therapy ( 11) . Prolonged treatment times (or for rapidly dividing tumors-routine treatment schedules) allow for accelerated repopulation during the last few weeks of therapy. Reduction in overall treatment time combined with high total doses, may overcome the