Phase I Study of Accelerated Hypofractionated Proton Therapy and Chemotherapy for Locally Advanced Non-Small Cell Lung Cancer
Mené entre 2015 et 2016 sur 20 patients atteints d'un cancer du poumon non à petites cellules de stade II-III (âge médian : 66,5 ans ; 60 % d'hommes ; durée médiane de suivi : 20,3 mois), cet essai de phase I évalue la dose maximale tolérée d'une protonthérapie hypofractionnée administrée en combinaison avec une chimiothérapie à base de carboplatine et de paclitaxel
Purpose: To evaluate the maximum tolerated dose (MTD) of hypofractionated proton beam radiation therapy (PBT) with concurrent weekly carboplatin/paclitaxel in patients with stage II-III non-small cell lung cancer (NSCLC). Materials/Methods: A phase I trial was designed using the Time to Event–Continuous Reassessment Method (TITE-CRM). MTD was defined as the dose associated with a 20% probability of CTCAE protocol-specified serious adverse events (SAEs). Starting dose was 3.5 Gy/fx for 15 fractions with 2 potential escalation and de-escalation levels in 0.25 Gy/fx increments. Chemotherapy was weekly concurrent carboplatin/paclitaxel with 2 cycles of optional consolidation carboplatin/paclitaxel. Results: From 5/2015-9/2016, 23 patients enrolled at a single institution. Of 20 evaluable, median age was 66.5 years (range, 54-89) and 12 (60%) were male. Fourteen had squamous cell (70%), and 15 (75%) were stage IIIA. Nineteen (95%) completed all 3 cycles of concurrent chemotherapy, and 16 (80%) received at least one cycle of consolidation chemotherapy. Within the 6-month TITE-CRM assessment window, no SAEs were reported, and most patients were treated at the highest dose-level. Dose-level assignment was 52.5 Gy (n=2), 56.25 Gy (n=4), and 60 Gy (n=14). The posterior probability of dose limiting toxicity (DLT) for 60 Gy was 5.3% (95% CI, 1-18.1%). Acute, non-serious AEs included grade 2 esophagitis in 7 patients (35%) and grade 2 pneumonitis in 1 patient (5%). At a median follow-up of 20.3 months for all and 44.9 months for living patients, there were no grade 4 or 5 AEs, though there were three (21% at 24 months) SAEs outside of the dose-escalation window. The 2-year overall survival, local, regional, and distant control rates were 48%, 84%, 77%, and 79%, respectively. Conclusions: Hypofractionated PBT and chemotherapy up to 60 Gy in 15 fractions is acutely well tolerated, with high rates of locoregional control and overall survival, though late SAEs were noted.
International Journal of Radiation Oncology, Biology, Physics