Background
Phase 2 single-arm trial (CALGB 39808). 72 patients with limited-stage SCLC (disease confined to one hemithorax, ipsilateral hilar/mediastinal nodes, contralateral mediastinal/supraclavicular nodes). Enrolled at CALGB institutions. Investigated an accelerated hyperfractionated RT regimen delivering higher total dose than INT-0096.
Interventions and follow up
Arm A: Cisplatin 60 mg/m² day 1 + etoposide 120 mg/m² days 1–3 × 4 cycles + accelerated hyperfractionated RT 70 Gy in 7 weeks (1.8 Gy/fraction QD weeks 1–2, then 1.5 Gy BID weeks 3–7)
Primary endpoint: 2-year OS and feasibility
mFollow up: Median 28 month
Primary endpoint: 2-year OS and feasibility
mFollow up: Median 28 month
Results
2-yr OS: 48%
Median OS: 22.4 months
2-yr PFS: 29%
Grade ≥3 esophagitis: 26%
Median OS: 22.4 months
2-yr PFS: 29%
Grade ≥3 esophagitis: 26%
Adverse events
Main adverse events: Grade ≥3 esophagitis 26%, comparable to INT-0096 BID arm. Grade ≥3 neutropenia was the most common hematologic toxicity. Feasibility demonstrated: 88% completed planned RT. No unexpected fatal toxicities directly attributable to the RT regimen.
Conclusions
Accelerated hyperfractionated RT delivering 70 Gy over 7 weeks was feasible in limited SCLC with 2-year OS of 48%, comparable to or slightly better than INT-0096 results, suggesting dose escalation beyond 45 Gy may be feasible without prohibitive toxicity.
Key Limitations
Key Limitations: Single-arm phase 2 with no randomized comparator — direct comparison to INT-0096 is historical and confounded by patient selection and supportive care evolution. Complex fractionation schedule (QD weeks 1–2, then BID weeks 3–7) is logistically demanding. Small N=72. The apparent outcome improvement vs INT-0096 may reflect selection bias rather than true benefit from higher dose. No OS benefit has been confirmed in a phase 3 trial comparing 70 Gy to 45 Gy BID.
Clinical Context
CALGB 39808 provided early evidence that dose escalation beyond 45 Gy was feasible in limited SCLC. However, subsequent CONVERT (Faivre-Finn 2017) showed that 66 Gy QD had comparable OS to 45 Gy BID, suggesting 66 Gy QD may represent a practical alternative for modern practice. The optimal RT dose for limited SCLC — 45 Gy BID vs 66 Gy QD vs higher doses — remains an active investigation. The current North American standard remains 45 Gy BID starting with cycle 1 based on INT-0096 data.
References