An Overview of Fotemustine in High-Grade Gliomas: From Single Agent to Association with Bevacizumab

Table 2

The most important studies on fotemustine treatment during temozolomide era.

Authors	PTS	Median; age	Median KPS	Types of gliomas	Prior treatment	FTM schedule	Line of FTM treatment	DCR	PFS	OS	Grades 3-4 toxicity
Scoccianti et al., 2008 [17]	27	56	80 (70–100)	GBM	Surgery^§(93%),; RT + TMZ (100%)	Standard*	2nd	48% (PR 30%, SD 18%)	5.7 ms	9.1 ms	Thrombocytopenia 11%; leukopenia 4%
Brandes et al., 2009 [18]	43	51 (34–68)	90 (70–100)	GBM	Surgery^§ (93%), RT + TMZ (100%)	Standard*	2nd	42% (PR 7%, SD 35%)	1.7 ms	6 ms	Thrombocytopenia 15%; leukopenia 7%; nausea 5%; lymphopenia 10%; hypertransaminasemia 9%
Fabrini et al., 2009 [19]	50	56 (30–76)	90 (70–100)	GBM	Surgery^§ (94%), RT + TMZ (100%)	Standard*	2nd	62% (CR 2%, PR 16%, SD 44%)	6.1 ms	8.1 ms	Thrombocytopenia 8%; leukopenia 10%; nausea 2%; hypertransaminasemia 2%
Addeo et al., 2011 [20]	40	53 (30–75)	90 (70–100)	GBM	Surgery^§ (82%), RT + TMZ (100%)	FTM 80 mg/m^2 every 2 wks for 5 cycles followed, after a 5-week rest period, by FTM 80 mg/m^2 every 4 wks	2nd	65% (CR 2%, PR 23%, SD 40%)	6.7 ms	11 ms	Thrombocytopenia 7%; leukopenia 3%; Nausea 12%; hypertransaminasemia 10%
Fabi et al., 2010 [21]	40	57 (26–80)	80 (60–100)	GBM (75%), AA (15%), AOD (10%)	Surgery^§ (95%), RT (92%). TMZ (100%)	FTM 60 mg/m^2 weekly for 3 cycles followed, after a 5-wk rest period, by FTM 75 mg/m^2 every 3 wks	2nd and 3rd	52% (PR 20%, SD 32%)	3 ms	6 ms	Thrombocytopenia 7%; leukopenia 10%; nausea 2%; hypertransaminasemia 2%
Santoni et al., 2013 [22]	65	70 (≥65)	>70	GBM	Surgery^§ (82%), RT + TMZ (100%)	Standard*	2nd	43% (CR 1%, PR 18%, SD 28%)	4.2 ms	7.1 ms	Thrombocytopenia 15%; leukopenia 9%; hypertransaminasemia 5%; anemia 3%
Silvani et al., 2008 [23]	54	53 (26–68)	80 (60–100)	GBM	Surgery^§ (100%), RT (100%), TMZ (100%)	PCZ 450 mg days 1-2, 300 mg day 3; FTM 110 mg/m^2 day 3 every 5 weeks	2nd and 3rd	65% (PR 11%, SD 54%)	19.3 wks	28.7 wks	Thrombocytopenia 1%; leukopenia 3%; hypertransaminasemia 1%
Soffietti et al., 2012 [29]	32	46	NA	Grade III glioma	Surgery^§ (100%), RT + TMZ (100%)	FTM 75 mg/m^2 days 1, 8, BV 10 mg/Kg days 1, 15 followed, after a 3 wk rest period, by FTM 75 mg/m^2 + BV 10 mg/Kg day 1 every 3 wks	2nd	94% (CR 12%, PR 38%, SD 44%)	5 ms	8.6 ms	16% myelotoxicity
Soffietti et al., 2014 [28]	54	57	80 (60–100)	GBM	Surgery^§ (92%), RT (100%), TMZ (100%)	FTM 75 mg/m^2 days 1, 8, BV 10 mg/Kg days 1, 15 followed, after a 3 wk rest period, by FTM 75 mg/m^2 + BV 10 mg/Kg day 1 every 3 wks	2nd	89% (CR 4%, PR 48%, SD 37%)	5.2 ms	9.1 ms	Thrombocytopenia 9%; leukopenia 13%; hypertension 2%; PE and DVT 4%

FTM: fotemustine; KPS: Karnofsky performance status; RT: radiation therapy; CT: chemotherapy; PTS: patients; PFS: progression-free survival; OS: overall survival; DCR: disease control rate; GBM: glioblastoma; AA: anaplastic astrocytoma; AOA: anaplastic oligoastrocytoma; PCZ: procarbazine; CDDP: cisplatin; VP16: etoposide; BV: bevacizumab; PE: pulmonary embolism; DVT: deep venous thrombosis; wk: week; ms: months; CR: complete response; SD: stable disease; PR: partial response; NA: not available.
∗Standard: FTM 100 mg/m² every week for 3 consecutive weeks followed by a 5-week rest period, subsequently, an infusion every 3 weeks; §Surgery: complete or partial resection.