P17.14 * A PROPOSAL OF A MODIFIED STUPP'S SCHEDULE WITH PROLONGED ADJUVANT TEMOZOLOMIDE: EXPERIENCE OF A SINGLE INSTITUTION IN A SERIES OF 100 CONSECUTIVE GBM PATIENTS
Authors: M. Caroli, M. Minichiello, A. Di Cristofori, G. Lanfranchi, G. Bertani, G. Carrabba, P. Rampini
Journal: Neuro-Oncology (2014)

BACKGROUND: Glioblastoma (GBM) is a primary malignant brain tumor and its evolution is generally rapidly fatal. The current standard of care for this disease is surgical resection followed by concomitant radiationtherapy plus chemiotherapy as described by Stupp and Colleagues. In this study we described our experience in a series of 100 consecutive patients affected by GBM treated with modified Stupp regimen at “Fondazione IRCCS Ca' Granda Ospedale Policlinico Maggiore” in Milan, Italy. METHODS: One hundred patients with newly diagnosed, histologically confirmed GBM were submitted to concomitant chemo-radiation therapy. Subjects who were not able to complete the concomitant phase of chemo-radiation therapy were excluded from this study.The diagnosis was obtained after surgical resection or stereotactic biopsy and then all the patients were treated with radiationtherapy plus continuous daily temozolomide (TMZ) according to a modified Stupp's schedule. In the adjuvant phase we administered a modified schedule consisting of 150mg/mq of TMZ, from day 1 to 5 and 75 mg/mq of TMZ from day 6 to 10 for 12 cycles instead of the 6 standard cycles proposed by Stupp and Colleagues. At recurrence, various strategies were chosen according the patients clinical and radiological status. After the concomitant phase, patients underwent a regular follow-up with a clinical examination and a brain MRI with gadolinium every 3 months. MGMT status was assessed according the method described by Hegi et al. in 2005 and was retrospectively re-evaluated with PCR real time (Pyromark Q96ID System). RESULTS: One hundred patients affected by GBM were included (60 males; 40 females; median age 61). The median KPS at presentation was 70 (range= 40- 100) which remained stable after 6 months. Median Ki67 was 10%. In 63 patients MGMT was methylated (38 males; 25 females. Median TTP-1 was of 12 months) and in 32 patients were MGMT un-methylated (male 21; females11; median TTP-1 of 9 months); in 5 cases we have no data. Surgical resection was done in 92 patients whereas only in 8 cases weproceeded with stereotactic biopsy alone. Gross total resection (>95%) was achieved in 57 patients; while 35 patients receibed a sub-total resection (85-95%).Median Overall survival (OS) was 16 months and TTP-1 and time to tumor progression after recurrence (TTP-2) was 11 months in MGMT methylated patients and 4 months in MGMT un-methylated patients. At a median follow up of 12 months, 24 months and 36 months our OS was 81%, 33% and 20% respectively compared to the historical group described by Stupp in 2005 which were 61% at 12 months and 27.5% at 24 months and 16% at 36 months. Data about the comparison of MGMT status assessment will be discussed at the time of the meeting. CONCLUSION: According the data collected, our modified adjuvant schedule can be useful for increasing the therapeutic effect of TMZ and can contribute to prolong the TTP.