Long-term outcomes of interventions for radiation-induced xerostomia: A review

Table 2 Amifostine: Xerostomia

Author	Type of study	n	Intervention	Xerostomia symptoms	Effect Size
Bardet et al[46], 2011	Phase III randomized trial	291	Amifostine IV vs SC	RTOG grading: G2+ xero significantly higher in SC at 1 yr, but not at 2-3 yr	37% IV vs 62% SC
Haddad et al[45], 2009	Phase II randomized trial	58	SC amifostine 500 mg daily (for median 28 doses) no amifostine	CTCAE: no significant difference in Gr2+ xero (minimum follow up 26 mo)	41% both arms
Law et al[44], 2007	Phase II prospective nonrandomized trial	20	SC 500 mg amifostine 30-60 min before RT	G2 xero 42% at 12 mo, 29% at 18 mo; no G3+ xero. G3+ mucositis in 30% of pts.
Anné et al[43], 2007	Phase II single arm multicenter trial	54	SC amifostine	RTOG scoring: G2+ xero = 56%; late G2+ in 45% ; G3+ acute 33%
Jellema et al[23], 2006	Phase II randomized trial	91	No amifostine vs 200 mg/m2 IV daily (3 wk) vs 5 wk	RTOG scoring: significant difference in late G2+ xero at 6 mo between arms; no difference in xero at 12 mo or 24 mo; no dif in acute xero	Late G2+ xero 74% vs 67% vs 52%
				EORTC QLQ-H and N35: significantly higher mean xerostomia score in no amifostine group
Buentzel et al[41], 2006	Phase III randomized placebo-controlled trial	132	IV amifostine 300 mg/m2 days 1-5 and 21-25, 200 mg/m2 on other days vs placebo	RTOG criteria: no significant difference in G2+ acute or late xero	39% amifostine vs 34% placebo (acute); 39% amifostine vs 24% placebo (late)
Wasserman et al[42], 2005	Phase III randomized trial	303	IV amifostine 200 mg/m2 15-30 prior to each RT fraction vs no amifostine	RTOG scoring: significantly lower G2+ xero in amifostine group on longitudinal analysis	20% vs 36% at 24 mo
Thorstad et al[47], 2004	Pilot clinical trial	27	Amifostine concurrent with RT (500 mg SC daily)	not reported	NA
Antonadou et al[40], 2002	Randomized controlled trial	50	Amifostine 300 mg/m2 15-30 min prior to RT (daily) vs no amifostine	RTOG/EORTC scoring: significantly lower xero in amifostine group at 18 mo (G1+)	30.4% vs 4.5%
Brizel et al[39], 2000	Phase III multiinstitutional randomized trial	303	Amifostine 200 mg/m2 15-30 min prior to each RT tx vs no amifostine	RTOG scoring: significantly higher G2+ xero (acute and late) in control vs amifostine; higher dose required to cause G2 xero in amifostine pts (60 Gy vs 42 Gy);	78% vs 51% (acute); 57% 43% (1 yr)
Büntzel et al[38], 1998	Phase II randomized trial	39	Amifostine IV 500mg prior to carboplatin (days 1-5 and 21-25) vs no amifostine	Acute G2 xero, G3 mucositis, and G3 thrombocytopenia all significantly decreased with amifostine; at 12 mo, trend toward xero improvement with amifostine	Xero: G2 100% vs 12% (acute); 55% vs 17% (late; P = 0.05)

SC: Subcutaneous; G: Grade; xero: Xerostomia; pts: Patients.