Phase I Dose Escalation Study of Accelerated Radiation Therapy with Concurrent Chemotherapy for Locally-Advanced Lung Cancer
Mené sur 24 patients atteints d'un cancer du poumon de stade localement avancé, cet essai de phase I évalue la dose maximale tolérée de rayonnements ionisants dans le cadre d'un traitement combinant de manière concomitante une chimiothérapie par cisplatine-étoposide et une radiothérapie avec modulation d'intensité délivrée selon un schéma accéléré
Purpose : To determine the maximum tolerated dose of radiation therapy (RT) given in an accelerated fashion with concurrent chemotherapy using intensity modulated RT (IMRT). Materials/Methods : Patients with locally-advanced lung cancer (non-small cell and small cell) with good performance status and minimal weight loss received concurrent cisplatin and etoposide with RT. IMRT with daily image guidance was utilized to facilitate esophageal avoidance and delivered using 6 fractions/week (bid on Fridays with 6 hour interval). The dose was escalated from 58 to a planned maximum dose of 74 Gy in 4 Gy increments in a standard 3+3 trial design. Dose-limiting toxicity (DLT) was defined as acute grade 3-5 non-hematologic toxicity attributed to radiation therapy. Results : 24 patients were enrolled, filling all dose cohorts, all completing RT and chemotherapy as prescribed. DLT occurred in 1 patient at 58 Gy (grade 3 esophagitis) and 1 patient at 70 Gy (grade 3 esophageal fistula). Both patients with DLTs had large tumors (12 cm and 10 cm, respectively) adjacent to the esophagus. Three additional patients were enrolled at both dose cohorts without further DLT. In the final 74 Gy cohort, no DLTs were observed (0/6). Conclusions : Dose escalation and acceleration to 74 Gy with IMRT and concurrent chemotherapy was tolerable with a low rate of of grade ≥ 3 acute esophageal reactions.