Table 1:
Selected randomised phase III studies with concurrent chemoradiotherapy in locally advanced SCCHN
| Number of patients |
Treatment schedule | Control arm | Primary endpoint |
Treatment outcome | |
|---|---|---|---|---|---|
| Chemoradiotherapy vs conventional radiotherapy alone as postoperative treatment | |||||
| Oral cavity, oropharynx, hypopharynx, larynx100 | 334 | Radiotherapy+C (100 mg/m2) d 1,22,43 | Radiotherapy | Progression-free survival | 47% vs 36% at 5 years, p=0·04 Overall survival 53% vs 40% at 5 years, p=0·04 |
| Oral cavity, oropharynx, hypopharynx, larynx101,102 |
416 | Radiotherapy+C (100 mg/m2) d 1,22,43 | Radiotherapy | Locoregional control | HR 0·61, 95% CI 0·41–0·91; p=0·01 Updated HR 0·72, 95% CI 0·48–1·06; p=0·08 |
| Oral cavity, oropharynx, hypopharynx, larynx103 | 444 | Radiotherapy+C (20 mg/m2 ci)+F (600 mg/m2 ci) d 1–5, 29–33 | Radiotherapy | Locoregional control | 88·3% vs 61·9% at 5 years, p=0·0006 Overall survival 58·1% vs 48·6%, p=0·11 |
| Chemoradiotherapy vs conventional radiotherapy alone as primary treatment | |||||
| Oropharynx104,105 | 222 (unresectable) | Radiotherapy+Cb (70 mg/m2, d 1–4)+F (600 mg/m2 ci, d 1–4) for 3 cycles | Radiotherapy | Overall survival | 51% vs 31% at 3 years, p=0·02 22·4% vs 15·8% at 5 years, p=0·05 |
| Oral cavity, oropharynx, hypopharynx, larynx106 | 295 (unresectable) | Radiotherapy+C (100 mg/m2) d 1,22,43 (A) or Radiotherapy split course+C (75 mg/m2 d 1)+F (1000 mg/m2 ci, d 1–4) for 3 cycles (B) | Radiotherapy (C) | Overall survival | (A) 23% vs (C) 37% (p=0·014) vs (B) 27% (p=NS) at 3 years |
| Larynx107,108 | 510 (resectable) | Radiotherapy+C (100 mg/m2) d 1,22,43 (A) or radiotherapy alone (B) | C (100 mg/m2 d 1)+F (1000 mg/m2/d ci d 1–5) for 3 cycles followed by radiotherapy alone in responders (C) | Laryngeal preservation | (A) 84% vs (B) 66% (p=0·00017) vs (C) 70% (p=0·0029), at 5 years |
| Chemoradiotherapy vs altered fractionation radiotherapy alone as primary treatment | |||||
| Oral cavity, oropharynx, hypopharynx, larynx109 | 270 (unresectable) | Hfx radiotherapy+C (60 mg/m2, d 1)+F (350 mg/m2 bolus, d 2)+Fo (50 mg/m2 bolus, d 2) or F (350 mg/m2 ci, d 2–5)+Fo (100 mg/m2 ci, d 2–5) for 3 cycles | Hfx radiotherapy | Locoregional control | 35% vs 17% at 3 years, p<0·004 Overall survival 49% vs 24%, p<0·0003 |
| Oral cavity, oropharynx, hypopharynx, larynx110 | 116 (62 unresectable) | Hfx radiotherapy (70 Gy)+C (12 mg/m2, d 1–5)+F (600 mg/m2 ci, d 1–5) weeks 1,6 | Hfx radiotherapy (75 Gy) | Locoregional control | 70% vs 44% at 3 years, p<0·01 Overall survival 55% vs 34%, p=0·07 |
| Oral cavity, oropharynx, hypopharynx, larynx111 | 130 | Hfx radiotherapy+C (6 mg/m2) per day | Hfx radiotherapy | Overall survival | 46% vs 25% at 5 years, p=0·0075 |
| Oropharynx112 | 192 (unresectable) | Radiotherapy (66–70 Gy)+Cb (75 mg/m2, d 1–4)+F (1000 mg/m2 ci, d 1–4) for 3 cycles | Conventional radiotherapy or Hfx Acc radiotherapy (64–67·2 Gy) | Overall survival | 51% vs 40% vs 37% at 2 years, p=0·129 |
| Oral cavity, oropharynx, hypopharynx, larynx113 | 224 (78 unresectable) | Hfx radiotherapy+C (20 mg/m2, d 1–5) for 2 cycles | Hfx radiotherapy | Time to treatment failure | 27% vs 24% at 5 years, p>0·05 Overall survival 46% vs 32% at 5 years, p=0·15 |
| Oral cavity, oropharynx, hypopharynx114 | 384 (unresectable) | Hfx Acc radiotherapy (70·6 Gy)+F (600 mg/m2 ci, d 1–5)+M (10 mg/m2 bolus) d 1,36 | Hfx Acc radiotherapy (77·6 Gy) | Locoregional control | 49·9% vs 37·4% at 5 years, p=0·001 Overall survival 28·6% vs 23·7% at 5 years, p=0·023 |
| Oropharynx, hypopharynx115,116 | 240 (unresectable) | Hfx Acc radiotherapy+Cb (70 mg/m2 d 1–4)+F (600 mg/m2 ci, d 1–4) for 2 cycles | Hfx Acc radiotherapy | Locoregional control | 22·7% vs 12·6% at 5 years, p=0·01 Overall survival 26·1% vs 13% at 5 years, p=0·008 |
Acc=accelerated. C=cisplatin. Cb=carboplatin. ci=continuous infusion. d=day of treatment cycle. F=fluorouracil. Fo=folinate. Hfx=hyperfractionated. HR=hazard ratio. M=mitomycin. NS=not significant. SCCHN=squamous cell carcinoma of the head and neck. Unresectable (inoperable) SCCHN is not defined uniformly; it is associated with worse outcomes vs resectable (operable) SCCHN.