Medical Treatment of Glioblastoma

Study (reference)

Number of patients

Treatment arms

PFS (months)

OS (months)

Comments

EORTC/NCI [1]

573

RT/TMZ versus RT

6.9 versus 5.0

15 versus 12

RT/TMZ superior to RT alone

RTOG 0525 [5]

833

Standard dose TMZ (days 1–5 every 28 days) versus dose-dense TMZ (days 1–21 every 28 days)

5.5 versus 6.7

17 versus 15

No significant improvement in OS or PFS with dose-dense TMZ/RT

RTOG 0825 [19]

637

RT/TMZ/Bev versus RT/TMZ

11 versus 7.3

16 versus 16

PFS longer in Bev group; no significant difference in OS

AVAGLIO [20]

921

RT/TMZ/Bev versus RT/TMZ

11 versus 6.2

17 versus 17

PFS longer in Bev group; no significant difference in OS

GLARIUS [21]

170

RT/TMZ/Bev + Bev/Iri^a versus RT/TMZ

9.7 versus 6.0

17 versus 15

PFS-6 in Bev/Iri arm superior unmethylated MGMT GBM

CENTRIC [24]

545

RT/TMZ/CIL versus RT/TMZ

13 versus 11

26 versus 26

CIL did not prolong PFS or OS in methylated MGMT GBM

CORE [25]

265

RT/TMZ/CIL₂ versus RT/TMZ/CIL₅ versus RT/TMZ

5.6 versus 5.9 versus 4.1

16 versus 14 versus 13

Median OS increased with addition of CIL₂ but not with CIL₅ in unmethylated MGMT GBM

RT/TMZ-radiation with concurrent temozolomide followed by adjuvant temozolomide; PFS progression-free survival; PFS 6-progression-free survival at 6 months; OS overall survival; RT radiation therapy; TMZ temozolomide; Bev bevacizumab; Iri irinotecan; MGMT O⁶-methylguanine DNA methyltransferase; CIL cilengitide; CIL ₂ cilengitide 2 times/week (standard dose); CIL ₅ cilengitide 5 times/week (dose intense)

^aBev/Iri substituted for adjuvant temozolomide

Table 2

Randomized trials in recurrent glioblastoma with medical therapies (last decade)

Study (reference)	Number of patients	Treatment	PFS (months)	OS (months)	Comments
Bev versus Bev/Iri [35]	167	Bev versus Bev/Iri	46 % versus 50 %^a	9.2 versus 8.7	No advantage to addition of irinotecan
Enzastaurin versus Lomustine [27]	266	Enzastaurin versus lomustine	1.5 versus 1.6	6.6 versus 7.1	PFS, OS not superior
REGAL [46]	325	Cediranib versus lomustine versus cediranib/lomustine	92 versus 82 versus 125 days	8.0 versus 9.8 versus 9.4	Cediranib-containing arms not superior to lomustine
CABARET [28]	122	Bev/Carboplatin versus Bev	26 % versus 24 %^a	6.9 versus 6.4	Bev/Carboplatin not superior
BELOB [44]	140	Bev versus Lomustine versus Bev/Lomustine	3 versus 2 versus 4	38 % versus 43 % versus 59 %^b	Bev/lomustine met primary endpoint of OS at 9 months (55 %). Phase III bev/lomustine versus lomustine ongoing

PFS progression-free survival; OS overall survival; Bev bevacizumab

^aPFS₆ (PFS at 6 months)

References

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Hegi ME, Diserens AC, Gorlia T et al (2005) MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med 352:997–1003PubMedCrossRef

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Westphal M, Hilt DC, Bortey E et al (2003) A phase 3 trial of local chemotherapy with biodegradable carmustine (BCNU) wafers (Gliadel wafers) in patients with primary malignant glioma. Neuro-oncology 5:79–88PubMedCentralPubMed

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