Table 2:
Selected phase III randomised trials of cisplatin-based induction chemotherapy in locally advanced SCCHN
| Number of patients |
Treatment schedule | Control arm | Primary endpoint |
Treatment outcome | |
|---|---|---|---|---|---|
| Induction chemotherapy followed by locoregional treatment vs locoregional treatment alone | |||||
| Larynx124 | 332 (resectable) | C (100 mg/m2, d 1)+F (1000 mg/m2 ci, d 1–5) every 3 weeks for 3 cycles followed by radiotherapy in responders | Surgery (followed by radiotherapy) | Survival or laryngeal preservation | 64% of survivors achieved laryngeal preservation. No difference in overall survival |
| Hypopharynx125 | 194 (resectable) | C (100 mg/m2, d 1)+F (1000 mg/m2 ci, d 1–5) every 3 weeks for 3 cycles followed by radiotherapy in responders | Surgery (followed by radiotherapy) | Efficacy equivalence | 35% laryngeal preservation at 5 years. Overall survival 57% vs 43% at 3 years (favouring induction) |
| Oropharynx133 | 318 | C (100 mg/m2, d 1)+F (1000 mg/m2 ci, d 1–5) every 3 weeks for 3 cycles followed by surgery or radiotherapy, or both | Surgery or radiotherapy, or both | Overall survival | Median survival, 5·1 years vs 3·3 years, p=0·03 |
| Oral cavity, oropharynx, hypopharynx, paranasal sinus131,132 | 237 (171 unresectable) | C (100 mg/m2, d 1)+F (1000 mg/m2 ci, d 1–5) every 3 weeks followed by surgery or radiotherapy, or both | Surgery or radiotherapy, or both | Overall survival | In unresectable, at 5 years, 21% vs 8%; 16% vs 6%, at 10 years, p=0·04 No statistically significant differences in resectable |
| Taxane plus cisplatin or fluorouracil vs cisplatin or fluorouracil alone | |||||
| Oral cavity, oropharynx, hypopharynx, larynx135 | 382 (248 unresectable) | P (175 mg/m2 d 1)+C (100 mg/m2, d 2)+F (500 mg/m2 ci, d 2–6) every 3 weeks for 3 cycles | P (100 mg/m2 d 1)+F (1000 mg/m2 ci, d 1–5) every 3 weeks for 3 cycles | Complete response rate | 33% vs 14%, p<0·001 Overall survival 66·5% vs 53·6% at 2 years, p=0·06 |
| Oral cavity, oropharynx, hypopharynx, larynx137 | 358 (unresectable) | D (75 mg/m2 d 1)+C (75 mg/m2, d 1)+F (750 mg/m2 ci, d 1–5) every 3 weeks for 4 cycles followed by radiotherapy | C (100 mg/m2 d 1)+F (1000 mg/m2, ci, d 1–5) every 3 weeks for 4 cycles followed by radiotherapy | Progression-free survival | Median progression-free survival, 11 months vs 8·2 months, p=0·007 Overall survival 37% vs 26% at 3 years, p=0·02 |
| Oral cavity, oropharynx, hypopharynx, larynx136 | 501 (176 unresectable) | D (75 mg/m2, d 1)+C (100 mg/m2, d 1)+F (1000 mg/m2 ci, d 1–4) every 3 weeks for 3 cycles followed by radiotherapy+Cb (AUC=1·5) every week | C (100 mg/m2, d 1)+F (1000 mg/m2, ci, d 1–5) every 3 weeks for 3 cyles followed by radiotherapy+Cb (AUC=1·5) every week | Overall survival | Median overall survival, 71 months vs 30 months, p=0·006,62% vs 48% at 3 years |
| Hypopharynx, larynx134 | 220 (resectable) | D (75 mg/m2 d 1)+C (75 mg/m2 d 1)+F (750 mg/m2 ci, d 1–5) every 3 weeks for 3 cycles followed by radiotherapy for responders | C (100 mg/m2 d 1)+F (1000 mg/m2 ci, d 1–5) every 3 weeks for 3 cycles followed by radiotherapy for responders | Laryngeal preservation rate | 73% vs 63% at 3 years, p=0·036 |
C=cisplatin. Cb=carboplatin. ci=continuous infusion. d=day of treatment cycle. D=docetaxel. F=fluorouracil. P=paclitaxel. HR=hazard ratio. SCCHN=squamous cell carcinoma of the head and neck. Unresectable (inoperable) SCCHN is not defined uniformly; it is associated with worse outcomes versus resectable (operable) SCCHN.