Phase I trial of the MEK inhibitor selumetinib in combination with thoracic radiotherapy in non-small cell lung cancer.

ABSTRACT:

Background

The RAS/RAF/MEK/ERK signalling pathway has a pivotal role in cancer proliferation and modulating treatment response. Selumetinib inhibits MEK and enhances effects of radiotherapy in preclinical studies.

Patients and methods

Single-arm, single-centre, open-label phase I trial. Patients with stage III NSCLC unsuitable for concurrent chemo-radiotherapy, or stage IV with dominant thoracic symptoms, were recruited to a dose-finding stage (Fibonacci 3 + 3 design; maximum number = 18) then an expanded cohort (n = 15). Oral selumetinib was administered twice daily (starting dose 50 mg) commencing 7 days prior to thoracic radiotherapy, then with radiotherapy (6-6.5 weeks; 60-66 Gy/30-33 fractions). The primary objective was to determine the recommended phase II dose (RP2D)

SUBMITTER: Haslett K 

PROVIDER: S-EPMC7970011 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature