A Phase 1/2 Study of Carbon Ion Radiotherapy with Concurrent Chemotherapy for Locally Advanced Uterine Cervical Squamous Cell Carcinoma (Protocol 1302)
Mené sur 22 patientes atteintes d'un carcinome épidermoïde du col utérin de stade localement avancé (durée médiane de suivi : 32 mois), cet essai de phase I/II évalue l'efficacité, du point de vue du contrôle local de la maladie et de la survie globale à 2 ans, et la toxicité d'une radiothérapie par ions carbone en combinaison avec une chimiothérapie concomitante, en fonction de la taille de la tumeur (taille inférieure ou égale à 7,1 cm ; taille supérieure à 7,1 cm)
Background : This study evaluated the safety and efficacy of carbon-ion radiotherapy (C-ion RT) with concurrent chemotherapy (chemo-C-ion RT) for locally advanced uterine cervical squamous cell carcinoma in a phase 1/2 clinical trial. Methods : Twenty-two patients were treated with C-ion RT with concurrent weekly cisplatin at a dose of 40 mg/m2. The phase 1 component evaluated the safety of 72.0 Gy [relative biological effectiveness (RBE)] of C-ion RT with concurrent chemotherapy. In the phase 2 component, the safety and efficacy of chemo-C-ion RT were assessed using the dose determined in phase 1. Results : The median follow-up period and tumor size were 32 months and 71 mm (range; 51-150 mm), respectively. No patient had dose-limiting toxicities in the phase 1 component; the recommended dose (RD) was determined to be 72.0 Gy (RBE) with 40 mg/m2 of cisplatin. In the phase 2 component, 2 patients developed grade 3 gastrointestinal tract toxicities. In patients treated with RD, the 2-year LC, LC including salvage therapy, and overall survival rates (OS) were 67%, 81%, and 82%, respectively. The 2-year LC and OS rates for patients with tumor sizes ≤7.1 cm were 92% and 100%, and for those with sizes >7.1 cm were 33% and 60%, respectively. Conclusions : C-ion RT with concurrent weekly cisplatin was tolerated by patients with locally advanced uterine cervical squamous cell carcinoma. There were good outcomes in patients with tumor sizes ≤7.1 cm but not in those with larger tumors. The results of the present study should be validated with larger multi-institutional prospective studies. Further study is needed and that perhaps incorporating carbon ion external beam radiation with brachytherapy will further reduce the risk of central recurrence.