Phase I Study of Accelerated Hypofractionated Radiotherapy with Concurrent Chemotherapy for Stage III Non-Small-Cell Lung Cancer: CALGB 31102 (Alliance)
Mené sur 22 patients atteints d'un cancer du poumon non à petites cellules de stade III et inopérable, cet essai de phase I évalue la toxicité d'une radiothérapie hypofractionnée accélérée en combinaison avec une chimiothérapie concomitante
Purpose : Investigate the safety of accelerated hypofractionated radiotherapy (AHRT) with concurrent chemotherapy (CT) for inoperable stage III non–small-cell lung cancer (NSCLC). Patients and Methods : The primary objectives were to define the maximally tolerable course of accelerated radiotherapy and describe toxicities of therapy. Total radiotherapy remained at 60 Gy. The number of once daily fractions in each successive cohort was reduced. Cohort 1: 60 Gy 27 fx, Cohort 2: 60 Gy 24 fx, Cohort 3: 60 Gy 22 fx, and Cohort 4 was 60 Gy 20 fx. Concurrent: weekly carboplatin AUC 2, paclitaxel 45 mg /m2. Consolidation: carboplatin AUC 6, paclitaxel 200 mg/m2 q3 weeks x 2 cycles. MTD: Of 6 pts/cohort, ≤ 2 pts develop ≥ grade 3 toxicity and ≤1 pt develops ≥ grade 4 toxicity. Results : 22 patients were accrued, of which 21 patients were evaluable between July 2012 and May 2014. Grade 5 toxicity occurred in 3 patients (1 pt cohort 2 (hemoptysis), 2 pts cohort 3 (hemoptysis, pneumonitis)). The MTD was defined by Cohort 2 (60Gy in 2.5 Gy/fx). Time to grade 5 toxicity: 9 months, 6 months, and 9 months after starting treatment. Median follow-up was 23.0 (7.6-30.6) months (living patients), median overall survival 19.3 (95% CI: 9.3-34.0) months, median PFS 12.2 months (95% CI 6.1-22.5m). Conclusion : Only modest hypofractionation was achievable due to long-term toxicities. Nevertheless, the MTD of 60 Gy given at 2.5 Gy/fx allows completion of RT in 20% fewer treatments than conventional therapy. Further investigation of AHRT may help to better define the therapeutic index.
http://www.redjournal.org/article/S0360-3016(18)30109-3/fulltext 2018