Fraction dose escalation of split-course concurrent chemoradiotherapy following induction chemo-immunotherapy in unresectable locally advanced oesophageal squamous carcinoma in China (GASTO-10102): a single-centre phase 1 study
Mené sur 18 patients atteints d'un carcinome épidermoïde de l'oesophage de stade localement avancé (durée médiane de suivi : 20,5 mois), cet essai de phase I évalue la faisabilité et la sécurité d'une radiochimiothérapie à doses croissantes de rayonnements après une chimio-immunothérapie d’induction
Background: The optimal fractionation patterns and safety of hypofractionated radiotherapy remain poorly defined in locally advanced oesophageal squamous cell carcinoma (LA-ESCC). We aimed to determine the maximum tolerated fraction dose (MTFD) of split-course concurrent chemoradiotherapy (CCRT) following induction chemo-immunotherapy in patients with LA-ESCC.
Methods: In this phase 1 study, patients (aged 18–80 years) with unresectable, histologically confirmed LA-ESCC (stage T1-4, N0-3, M0-1 disease; ECOG 0–1) were enrolled from one site in China (Sun yat-sen University Cancer Center, Guangzhou, Guangdong). Eligible participants had no prior treatment with chemotherapy, radiotherapy, surgery, or immunotherapy for ESCC and no evidence of deep ulceration on baseline esophagoscopy. Enrolled participants received two cycles of induction albumin-bound paclitaxel (260 mg/m2, d1), cisplatin (60 mg/m2, d1), and toripalimab (240 mg, d1) every three weeks, followed by definitive split-course radiotherapy with oral capecitabine (1000 mg/m2, twice daily on days 1–14 of each radiotherapy course). Radiotherapy was delivered in two courses separated by a 4-week break using volumetric modulated arc therapy. Three dose levels were evaluated sequentially in cohorts of six patients: level 1 (30 Gy in 10 fractions + 20 Gy in 10 fractions), level 2 (28 Gy in 7 fractions + 22 Gy in 10 fractions), and level 3 (25 Gy in 5 fractions + 25 Gy in 10 fractions). The primary endpoint was MTFD within 12 months after completion of CCRT. The primary endpoint and safety analysis were assessed in all patients who received any study treatment. The trial is registered with ClinicalTrials.gov, NCT06020885.
Findings: Between Aug 31, 2023, and July 23, 2024, 18 patients were enrolled (n = 6 per dose), and all completed split-course CCRT per protocol. The MTFD was not reached, and dose level 3 was tolerable. The most common grade 3 toxicity was lymphopenia (72.2%), followed by esophagitis (11.1%). No grade 4 or 5 toxicities occurred. The objective response rate after induction therapy was 100%. After CCRT, the clinical complete response rate was 83.3%. With a median follow-up of 20.5 months, median progression-free and overall survival were not reached; 1-year rates were 88.9% and 94.4%, respectively.
Interpretation: Fraction dose-escalated split-course CCRT following induction chemo-immunotherapy was feasible, well tolerated, and showed encouraging preliminary efficacy. Larger prospective studies are warranted.
eClinicalMedicine , article en libre accès, 2026