Efficacy and safety of carboplatin and pemetrexed followed by maintenance with pemetrexed for elderly patients with advanced non-squamous non-small cell lung cancer: A single-arm, open-label, multicenter, phase II study.

PURPOSE: Carboplatin plus pemetrexed followed by maintenance pemetrexed is expected to be well-tolerated by the elderly. This multicenter, prospective study examined the efficacy and tolerability of the regimen in elderly patients with previously untreated advanced non-squamous non-small cell lung cancer. METHODS: The primary endpoint was the 1-year survival rate, with secondary endpoints of response rate (RR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and adverse event rate. Efficacy was compared between patients with performance status (PS) 0 and 1. RESULTS: Forty-one patients were enrolled between March 2011 and April 2016. Median age was 76.0 years. The 1-year survival rate was 73% (95% confidence interval (CI), 56-84%). RR was 44%, DCR was 81%, median PFS was 7.2 months (95%CI, 3.98-9.20 months), and median OS was 17.4 months (95%CI, 13.60-22.83 months). Twenty-one patients (51%) transitioned to maintenance therapy. Toxicities of grade ≥ 3 during the induction phase included anemia (37%), thrombocytopenia (29%), neutropenia (22%), appetite loss (15%), nausea (10%), bacterial pneumonia (7%), febrile neutropenia (5%), and interstitial pneumonia (2%). Treatment was discontinued in two patients with interstitial pneumonia, but no deaths were encountered. During the maintenance phase, one patient needed dose reductions due to phlegmon. No significant difference in efficacy was seen between PS 0 and PS 1. CONCLUSION: Carboplatin and pemetrexed followed by maintenance pemetrexed for non-squamous non-small cell lung cancer in elderly patients appear effective and tolerable.

RanBPM, Muskelin, p48EMLP, p44CTLH, and the armadillo-repeat proteins ARMC8alpha and ARMC8beta are components of the CTLH complex.

Ran-binding protein in microtubule organising centre (RanBPM) was originally isolated as a protein that binds to the small GTPase Ran. Recently our group and other groups reported that RanBPM was associated with several proteins and composed a large protein complex. Here, we used tandem MS with an antibody against RanBPM to purify this complex from a soluble extract of HEK293 cells: we identified Muskelin, p48EMLP, p44CTLH, and the novel armadillo-repeat proteins ARMC8alpha and ARMC8beta as components. In RanBPM, Muskelin, p48EMLP, and p44CTLH we found LisH/CTLH motifs, which are present in proteins involved in microtubule dynamics, cell migration, nucleokinesis, and chromosome segregation. We renamed the 20S large protein complex the CTLH complex. The N-terminal 364 amino acids of ARMC8alpha and ARMC8beta were completely conserved, suggesting that these proteins are probably alternatively spliced products from the same gene. We confirmed the in vivo association of each component by co-immunoprecipitation assays with Cos-7 cells in which these components were exogenously overexpressed. A pull-down assay with bacterially-expressed Twa1 revealed binding of each in vitro-translated component to Twa1. Finally, we confirmed the cellular localization of these proteins. Taken together, our results reveal that RanBPM, ARMC8alpha, ARMC8beta, Muskelin, p48EMLP, and p44CTLH form complexes in cells.