TY - JOUR
T1 - Phase I trial of everolimus in combination with thoracic radiotherapy in non-small-cell lung cancer
AU - Deutsch, Eric
AU - Le Péchoux, C.
AU - Faivre, L.
AU - Rivera, S.
AU - Tao, Y.
AU - Pignon, J. P.
AU - Angokai, M.
AU - Bahleda, R.
AU - Deandreis, D.
AU - Angevin, E.
AU - Hennequin, C.
AU - Besse, B.
AU - Levy, A.
AU - Soria, J. C.
N1 - Publisher Copyright:
© 2014 The Author.
PY - 2015/6/1
Y1 - 2015/6/1
N2 - Background: This phase I study evaluated the safety and efficacy of the oral mTOR inhibitor everolimus in combination with thoracic radiotherapy followed by consolidation chemotherapy in locally advanced or oligometastatic untreated nonsmall- cell lung cancer (NSCLC). Patients and methods: Everolimus dose was escalated in incremental steps [sequential cohorts of three patients until the occurrence of dose-limiting toxicity (DLT)] and administered orally weekly (weekly group: dose of 10, 20 or 50 mg) or daily (daily group: 2.5, 5 or 10 mg), 1 week before, and during radiotherapy until 3.5 weeks after the end of radiotherapy. Two cycles of chemotherapy (cisplatin-navelbine) were administrated 4.5 weeks after the end of radiotherapy. Results: Twenty-six patients were included in two centers, 56% had adenocarcinoma and 84% had stage III disease. In the weekly group (12 assessable patients), everolimus could be administered safely up to the maximum planned weekly dose of 50 mg; however, one patient experienced a DLT of interstitial pneumonitis at the weekly dose level of 20 mg. In the daily group (9 assessable patients): one DLT of interstitial pneumonitis with a fatal outcome was observed at the daily dose level of 2.5 mg; two other DLTs (one grade 3 esophagitis and one bilateral interstitial pneumonitis) were found at the daily dose level of 5 mg. Overall there were five patients with G3-4 interstitial pneumonitis related to treatment. Among 22 assessable patients for response, there were 9 (41%) partial response and 7 (32%) stable disease. At a median follow-up of 29 months, the 2-year overall survival and progression-free survival actuarial rates were 31% and 12%, respectively. Conclusion: In previously untreated and unselected NSCLC patients, the recommended phase II dose of everolimus in combination with thoracic radiotherapy is 50 mg/week. Pulmonary toxicity is of concern and should be carefully monitored to establish the potential role of mTOR inhibitor with concomitant radiotherapy.
AB - Background: This phase I study evaluated the safety and efficacy of the oral mTOR inhibitor everolimus in combination with thoracic radiotherapy followed by consolidation chemotherapy in locally advanced or oligometastatic untreated nonsmall- cell lung cancer (NSCLC). Patients and methods: Everolimus dose was escalated in incremental steps [sequential cohorts of three patients until the occurrence of dose-limiting toxicity (DLT)] and administered orally weekly (weekly group: dose of 10, 20 or 50 mg) or daily (daily group: 2.5, 5 or 10 mg), 1 week before, and during radiotherapy until 3.5 weeks after the end of radiotherapy. Two cycles of chemotherapy (cisplatin-navelbine) were administrated 4.5 weeks after the end of radiotherapy. Results: Twenty-six patients were included in two centers, 56% had adenocarcinoma and 84% had stage III disease. In the weekly group (12 assessable patients), everolimus could be administered safely up to the maximum planned weekly dose of 50 mg; however, one patient experienced a DLT of interstitial pneumonitis at the weekly dose level of 20 mg. In the daily group (9 assessable patients): one DLT of interstitial pneumonitis with a fatal outcome was observed at the daily dose level of 2.5 mg; two other DLTs (one grade 3 esophagitis and one bilateral interstitial pneumonitis) were found at the daily dose level of 5 mg. Overall there were five patients with G3-4 interstitial pneumonitis related to treatment. Among 22 assessable patients for response, there were 9 (41%) partial response and 7 (32%) stable disease. At a median follow-up of 29 months, the 2-year overall survival and progression-free survival actuarial rates were 31% and 12%, respectively. Conclusion: In previously untreated and unselected NSCLC patients, the recommended phase II dose of everolimus in combination with thoracic radiotherapy is 50 mg/week. Pulmonary toxicity is of concern and should be carefully monitored to establish the potential role of mTOR inhibitor with concomitant radiotherapy.
KW - Concomitant combination
KW - Everolimus
KW - Non-small-cell lung cancer
KW - Phase I
KW - Thoracic radiotherapy
UR - http://www.scopus.com/inward/record.url?scp=84938079441&partnerID=8YFLogxK
U2 - 10.1093/annonc/mdv105
DO - 10.1093/annonc/mdv105
M3 - Article
C2 - 25701455
AN - SCOPUS:84938079441
SN - 0923-7534
VL - 26
SP - 1223
EP - 1229
JO - Annals of Oncology
JF - Annals of Oncology
IS - 6
ER -