Platinum-based

Trial Patients Primary treatment Adjuvant therapy Grade 3 and 4 toxic effects Increased local control rate Difference in overall survival in favor of chemoradiotherapy
EORTC^a 22931 (2004)^[13] 167 with high-risk features on pathology Surgery CRT (P); RT alone^c Acute: CRT 41%; RT 21% Chronic: difference NS Yes: CRT 82%; RT 69% (at 5 years) Yes: CRT 53%; RT 40% (at 5 years)
RTOG^a 9501 (2004)^[14] 459 with high-risk features on pathology Surgery CRT (P); RT alone^c Acute: CRT 77%; RT 34% Chronic: difference NS Yes: CRT 82%; RT 72% (at 2 years) No: CRT ~65.0%; RT ~57.5% (at 2 years – but significant difference in DFS)
Bachaud et al. (1996)^[17] 83 with high-risk features on pathology Surgery CRT (P); RT alone Acute: CRT 41%; RT 18% Chronic: difference NS Yes: CRT 77%; RT 59% (at 4 years) Yes: CRT 72%; RT 46% (at 2 years)
Intergroup 91-11 Larynx (2003)^[15] 510 with laryngeal cancer CRT (P); RT plus induction chemotherapy; RT alone NA Acute: CRT 77%; RT + I 51%; RT 47%^a Chronic: CRT 30%; RT + I 24%; RT 36% (difference NS) Yes: CRT 80%; RT + I 64%; RT 58% (at 2 years) No: CRT 76%; RT + I 74%; RT 75% (at 2 years) but increased larynx preservation (CRT 88%; RT + I 75%; RT 70%)
Al-Sarraf et al. (1998)^[25] 193 with NPC CRT (P) plus consolidation with PF; RT alone NA Acute: CRT 75.6%; RT 50% Chronic: not reported Yes: CRT 89.2%; RT 74.0% Yes: CRT 76%; RT 46% (3-year OS)
Adelstein et al. (2003)^[24] 295 with unresectable tumors RT alone; CRT (P); CRT (PF) split course^b NA Acute: RT 52%; CRT 85%^a; CRT^b 72% Chronic: not reported Not reported but raised CR rate after therapy: RT 27%; CRT 41%; CRT^b 37% Yes: RT 23%; CRT 37%^e; CRT^b 27% (3-year OS)
Jeremic et al. (2000)^[37] 130 with stage III or IV disease HFX (RT); HFX (CRT and daily P)^f NA Acute: difference NS^d Chronic: difference NS Yes: RT 27%; CRT 53% Yes: RT 25%; CRT 46% (5-year OS)

Trial	Patients	Primary treatment	Adjuvant therapy	Grade 3 and 4 toxic effects	Increased local control rate	Difference in overall survival in favor of chemoradiotherapy
EORTC^a 22931 (2004)^[13]	167 with high-risk features on pathology	Surgery	CRT (P); RT alone^c	Acute: CRT 41%; RT 21% Chronic: difference NS	Yes: CRT 82%; RT 69% (at 5 years)	Yes: CRT 53%; RT 40% (at 5 years)
RTOG^a 9501 (2004)^[14]	459 with high-risk features on pathology	Surgery	CRT (P); RT alone^c	Acute: CRT 77%; RT 34% Chronic: difference NS	Yes: CRT 82%; RT 72% (at 2 years)	No: CRT ~65.0%; RT ~57.5% (at 2 years – but significant difference in DFS)
Bachaud et al. (1996)^[17]	83 with high-risk features on pathology	Surgery	CRT (P); RT alone	Acute: CRT 41%; RT 18% Chronic: difference NS	Yes: CRT 77%; RT 59% (at 4 years)	Yes: CRT 72%; RT 46% (at 2 years)
Intergroup 91-11 Larynx (2003)^[15]	510 with laryngeal cancer	CRT (P); RT plus induction chemotherapy; RT alone	NA	Acute: CRT 77%; RT + I 51%; RT 47%^a Chronic: CRT 30%; RT + I 24%; RT 36% (difference NS)	Yes: CRT 80%; RT + I 64%; RT 58% (at 2 years)	No: CRT 76%; RT + I 74%; RT 75% (at 2 years) but increased larynx preservation (CRT 88%; RT + I 75%; RT 70%)
Al-Sarraf et al. (1998)^[25]	193 with NPC	CRT (P) plus consolidation with PF; RT alone	NA	Acute: CRT 75.6%; RT 50% Chronic: not reported	Yes: CRT 89.2%; RT 74.0%	Yes: CRT 76%; RT 46% (3-year OS)
Adelstein et al. (2003)^[24]	295 with unresectable tumors	RT alone; CRT (P); CRT (PF) split course^b	NA	Acute: RT 52%; CRT 85%^a; CRT^b 72% Chronic: not reported	Not reported but raised CR rate after therapy: RT 27%; CRT 41%; CRT^b 37%	Yes: RT 23%; CRT 37%^e; CRT^b 27% (3-year OS)
Jeremic et al. (2000)^[37]	130 with stage III or IV disease	HFX (RT); HFX (CRT and daily P)^f	NA	Acute: difference NS^d Chronic: difference NS	Yes: RT 27%; CRT 53%	Yes: RT 25%; CRT 46% (5-year OS)