Background
Phase III, open-label, randomized (Singapore SQNP01). N=221, AJCC/UICC stage III–IV endemic NPC (predominantly WHO type II/III non-keratinizing/undifferentiated). Enrolled Singapore 1997–2003. Designed to confirm INT 0099 in an endemic population.
Interventions and follow up
Arm A (RT alone): RT 70 Gy alone
Arm B (CRT + adjuvant): concurrent cisplatin 25 mg/m²/day × 4 days q3wk × 3 with RT 70 Gy, then adjuvant cisplatin 20 mg/m²/day + 5-FU 1000 mg/m²/day × 4 days q4wk × 3
Primary endpoint: distant metastasis-free survival; OS
mFollow up: 3.2 yr
Arm B (CRT + adjuvant): concurrent cisplatin 25 mg/m²/day × 4 days q3wk × 3 with RT 70 Gy, then adjuvant cisplatin 20 mg/m²/day + 5-FU 1000 mg/m²/day × 4 days q4wk × 3
Primary endpoint: distant metastasis-free survival; OS
mFollow up: 3.2 yr
Results
2-yr cumulative distant metastasis difference: 17% (38 vs 18 events), P=.0029
DFS HR: 0.57 (95% CI 0.38–0.87), P=.0093
3-yr OS: 80% (CRT) vs 65% (RT), HR 0.51 (95% CI 0.31–0.81), P=.0061
DFS HR: 0.57 (95% CI 0.38–0.87), P=.0093
3-yr OS: 80% (CRT) vs 65% (RT), HR 0.51 (95% CI 0.31–0.81), P=.0061
Adverse events
Grade ≥3 (CRT arm): mucositis 19%, neutropenia 14%, nausea/vomiting 10%
Treatment delays/dose mods (CRT): 20%
Grade ≥3 late toxicity: comparable between arms (~15%)
Note: cisplatin dose lower than INT 0099 (25 mg/m²/d × 4 vs 100 mg/m² bolus) for endemic tolerability
Treatment delays/dose mods (CRT): 20%
Grade ≥3 late toxicity: comparable between arms (~15%)
Note: cisplatin dose lower than INT 0099 (25 mg/m²/d × 4 vs 100 mg/m² bolus) for endemic tolerability
Conclusions
Concurrent + adjuvant chemoradiation improved DFS and OS vs RT alone in endemic (WHO II/III) NPC, confirming INT 0099 in a Southeast Asian population; distant metastasis control improved by 17% absolute.
Key Limitations
Open-label; modified cisplatin dosing limits direct comparison to INT 0099; short median follow-up (3.2 yr); endemic histology limits generalizability to keratinizing/Western NPC; 2D/3D-conformal RT era (pre-IMRT).
Clinical Context
Established concurrent chemoradiation ± adjuvant chemo as standard for locoregionally advanced endemic NPC; reinforced INT 0099 outside Western cohorts. Subsequently refined by induction-chemo era trials.