Accelerated intensity-modulated radiotherapy plus temozolomide in patients with glioblastoma: a phase I dose-escalation study (ISIDE-BT-1)

作者：Massaccesi Mariangela; Ferro Marica; Cilla Savino; Balducci Mario; Deodato Francesco; Macchia Gabriella^*; Valentini Vincenzo; Morganti Alessio G

来源：International Journal of Clinical Oncology, 2013, 18(5): 784-791.

DOI：10.1007/s10147-012-0462-0

• Glioblastoma
• Radiotherapy
• IMRT
• Phase I
• Temozolomide

We performed a dose-escalation trial to determine the maximum tolerated dose (MTD) of intensity-modulated radiotherapy (IMRT) with standard concurrent and sequential-dose temozolomide (TMZ) in patients with glioblastoma multiforme. %26lt;br%26gt;Histologically proven glioblastoma patients underwent IMRT dose escalation. IMRT was delivered over 5 weeks with the simultaneous integrated boost (SIB) technique to the two planning target volumes (PTVs) defined by adding 5-mm margin to the respective clinical target volumes (CTVs). CTV1 was the tumor bed plus the enhancing lesion with 10-mm margin; CTV2 was the area of perifocal edema with 20-mm margin. Only the PTV1 dose was escalated (planned dose escalation: 60, 62.5, 65, 67.5, 70 Gy) while the PTV2 dose remained the same (45 Gy). %26lt;br%26gt;Forty consecutive glioblastoma patients were treated. While no dose-limiting toxicity (DLT) was recorded during the dose escalation up to 67.5/2.7 Gy, two out of the first six consecutively enrolled patients on the highest dose level (70/2.8 Gy) experienced a DLT, and therefore a cohort expansion was required. 3/14 patients experienced a DLT on the highest planned dose level, and therefore the MTD was not exceeded. After a median follow-up time of 25 months no grade %26gt; 2 late neurological toxicity was recorded. %26lt;br%26gt;By using a SIB IMRT technique, a radiation dose of 70 Gy in 25 fractions (biological effective dose-BED-of 92.8 Gy) can be delivered with concurrent and sequential standard dose TMZ, without unacceptable acute toxicity in patients with glioblastoma.

• 出版日期2013-10