Background
Phase III randomized Intergroup study (INT 0099 / SWOG S8892). 193 registered; 147 eligible for primary analysis. Advanced (stage III–IV) nasopharyngeal carcinoma (NPC), all histologies, US SWOG/RTOG/ECOG sites. RT 70 Gy in both arms.
Interventions and follow up
Arm A (RT alone): Conventional RT 70 Gy alone
Arm B (CRT + adjuvant): Concurrent cisplatin 100 mg/m² q3wk × 3 with RT 70 Gy, then adjuvant cisplatin 80 mg/m² day 1 + 5-FU 1000 mg/m² days 1–4 q4wk × 3
Primary endpoint: Progression-free survival and overall survival
mFollow up: NR (3-year data reported)
Arm B (CRT + adjuvant): Concurrent cisplatin 100 mg/m² q3wk × 3 with RT 70 Gy, then adjuvant cisplatin 80 mg/m² day 1 + 5-FU 1000 mg/m² days 1–4 q4wk × 3
Primary endpoint: Progression-free survival and overall survival
mFollow up: NR (3-year data reported)
Results
3-yr PFS: 69% (CRT) vs 24% (RT); P<.001
3-yr OS (eligible): 78% vs 47%; P=.005
3-yr OS (all randomized): 76% vs 46%; P<.001
Contralateral neck failure: Significantly reduced with CRT
3-yr OS (eligible): 78% vs 47%; P=.005
3-yr OS (all randomized): 76% vs 46%; P<.001
Contralateral neck failure: Significantly reduced with CRT
Adverse events
Grade ≥3 toxicity: Significantly higher with CRT
More frequent with CRT: neutropenia, mucositis, nausea/vomiting, hematologic toxicity
Adjuvant completion: 61% of eligible received all 3 cycles
Treatment-related death: 2 patients (CRT)
More frequent with CRT: neutropenia, mucositis, nausea/vomiting, hematologic toxicity
Adjuvant completion: 61% of eligible received all 3 cycles
Treatment-related death: 2 patients (CRT)
Conclusions
Concurrent cisplatin chemoradiotherapy plus adjuvant cisplatin/5-FU significantly improved PFS and OS vs RT alone for advanced NPC, establishing concurrent chemoradiotherapy as the standard of care and transforming NPC management globally.
Key Limitations
Predominantly non-endemic/keratinizing US population (limits generalizability to endemic EBV-related NPC); high attrition during adjuvant phase (61% completion); 2D RT era; cannot isolate concurrent vs adjuvant chemotherapy contribution.
Clinical Context
Practice-defining landmark establishing concurrent cisplatin chemoradiotherapy for locoregionally advanced NPC; foundation for subsequent endemic-population confirmatory trials and induction/adjuvant refinements.