scholarly journals Population pharmacokinetic modeling of PF-06439535 (a bevacizumab biosimilar) and reference bevacizumab (Avastin®) in patients with advanced non-squamous non-small cell lung cancer

2019 ◽  
Vol 85 (3) ◽  
pp. 487-499
Author(s):  
Cheryl S. W. Li ◽  
Kevin Sweeney ◽  
Carol Cronenberger
Keyword(s):  
Lung Cancer ◽  
Body Weight ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Drug Product ◽  
Compartment Model ◽  
Small Cell ◽  
Small Cell Lung ◽  
Covariate Analysis ◽  
Two Compartment Model

Abstract Purpose The objectives of this analysis were to characterize the population pharmacokinetics (PK) of PF-06439535 (a bevacizumab biosimilar) and reference bevacizumab (Avastin®) sourced from the European Union (bevacizumab-EU) in patients with advanced non-squamous non-small cell lung cancer (NSCLC), and to quantify the difference in PK parameters between the two drug products via covariate analysis. Methods Pooled PF-06439535 and bevacizumab-EU serum concentration data from a comparative clinical efficacy and safety study (NCT02364999) in patients with NSCLC (N = 719) were analyzed using a non-linear mixed-effects modeling approach. Patients received PF-06439535 plus chemotherapy or bevacizumab-EU plus chemotherapy every 21 days for 4–6 cycles, followed by monotherapy with PF-06439535 or bevacizumab-EU. PF-06439535 or bevacizumab-EU was administered intravenously at a dose of 15 mg/kg. Effects of patient and disease covariates, as well as the drug product (PF-06439535 versus bevacizumab-EU), on PK were investigated. Results Overall, 8632 serum bevacizumab concentrations from 351 patients in the PF-06439535 group and 354 patients in the bevacizumab-EU group were included in the analysis. A two-compartment model adequately described the combined data. Clearance (CL) and central volume of distribution (V1) estimates were 0.0113 L/h and 2.99 L for a typical 71-kg female patient with NSCLC administered bevacizumab-EU. CL and V1 increased with body weight and were higher in males than females even after accounting for differences in body weight. The 95% confidence intervals for the effect of drug product on CL and V1 encompassed unity. Conclusions The population PK of PF-06439535 and bevacizumab-EU were well characterized by a two-compartment model. Covariate analysis did not reveal any appreciable differences between PK parameters for PF-06439535 and bevacizumab-EU in patients with NSCLC. Clinical trial registration ClinicalTrials.gov, NCT02364999.

scholarly journals Early body weight loss during concurrent chemo-radiotherapy for non-small cell lung cancer

2014 ◽  
Vol 5 (2) ◽  
pp. 127-137 ◽  
Author(s):  
Céline M. H. Op den Kamp ◽  
Dirk K. M. De Ruysscher ◽  
Marieke van den Heuvel ◽  
Meike Elferink ◽  
Ruud M. A. Houben ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Weight Loss ◽  
Body Weight ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Body Weight Loss ◽  
Small Cell ◽  
Small Cell Lung

scholarly journals Aspirin potentiates celecoxib-induced growth inhibition and apoptosis in human non-small cell lung cancer by targeting GRP78 activity

2020 ◽  
Vol 12 ◽  
pp. 175883592094797
Author(s):  
Xiangyu Zhang ◽  
Jia Chen ◽  
Cheng Cheng ◽  
Ping Li ◽  
Fangfang Cai ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Cycle ◽  
Body Weight ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Mapk Signaling ◽  
Small Cell ◽  
Migration And Invasion ◽  
Small Cell Lung

Background: Aspirin has recently emerged as an anticancer drug, but its therapeutic effect on lung cancer has been rarely reported, and the mechanism of action is still unclear. Long-term use of celecoxib in large doses causes serious side effects, and it is necessary to explore better ways to achieve curative effects. In this study, we evaluated the synergistic anticancer effects of celecoxib and aspirin in non-small cell lung cancer (NSCLC) cells. Methods: In vitro, we evaluated the combined effects of celecoxib (40 μM) and aspirin (8 mM) on cell apoptosis, cell cycle distribution, cell proliferation, cell migration and signaling pathways. Furthermore, the effect of aspirin (100 mg/kg body weight) and celecoxib (50 mg/kg body weight) on the growth of xenograft tumors was explored in vivo. Results: Our data suggest that cancer sensitivity to combined therapy using low concentrations of celecoxib and aspirin was higher than that of celecoxib or aspirin alone. Further research showed that the anti-tumor effect of celecoxib combined with aspirin was mainly produced by activating caspase-9/caspase-3, arresting cell cycle and inhibiting the ERK-MAPK signaling pathway. In addition, celecoxib alone or in combination with aspirin inhibited the migration and invasion of NSCLC cells by inhibiting MMP-9 and MMP-2 activity levels. Moreover, we identified GRP78 as a target protein of aspirin in NSCLC cells. Aspirin induced an endoplasmic reticulum stress response by inhibiting GRP78 activity. Furthermore, combination therapy also exhibited a better inhibitory effect on tumor growth in vivo. Conclusions: Our study provides a rationale for further detailed preclinical and potential clinical studies of the combination of celecoxib and aspirin for NSCLC therapy.

Increased serum levels of ghrelin at diagnosis mediate body weight loss in non-small cell lung cancer (NSCLC) patients

Lung Cancer ◽  
2009 ◽  
Vol 66 (3) ◽  
pp. 393-398 ◽  
Author(s):  
Eleni M. Karapanagiotou ◽  
Aristidis Polyzos ◽  
Kalliopi D. Dilana ◽  
Ioannis Gratsias ◽  
Paraskevi Boura ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Weight Loss ◽  
Body Weight ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Body Weight Loss ◽  
Serum Levels ◽  
Small Cell ◽  
Small Cell Lung ◽  
Nsclc Patients

scholarly journals Acceptability, Compliance, and Safety of Non-small Cell Lung Cancer Cachectic Participants Continuing Compassionate Access in the ACCeRT Clinical Study

2021 ◽  
Author(s):  
Elaine S Rogers ◽  
Rita Sasidharan ◽  
Graeme M Sequeira ◽  
Matthew R Wood ◽  
Stephen P Bird ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Body Weight ◽  
Resistance Training ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Cancer Cachexia ◽  
Small Cell ◽  
Fat Free Mass ◽  
Compassionate Use ◽  
Small Cell Lung

Objective: Cancer cachexia is defined as: a ‘multifactorial syndrome’, and it has been suggested that a multitargeted approach is required in its management. High prevalence is seen within non-small cell lung cancer, and patients may continue to experience cachexia post end of anti-cancer treatment, and in the late/end stage.Material and Methods: Participants who had completed week 20/End of Trial visit in the main Auckland’s Cancer Cachexia evaluating Resistance Training (ACCeRT) study were invited to continue with treatment under compassionate use. Participants could continue with 2.09 g of eicosapentaenoic acid (EPA), 300 mg COX-2 inhibitor (celecoxib), once daily; plus two sessions per week of progressive resistance training (PRT), and 20 g oral essential amino acids (EAA); high in leucine, in a split dose over three days post each session. Data was collected on the acceptability, compliance and adherence to medication/PRT sessions. Secondary endpoints included: change in body weight and fat free mass, handgrip and leg strength, the Functional Assessment of Anorexia/Cachexia Therapy, Multidimensional Fatigue Symptom Inventory-Short Form, World Health Organization Quality of Life — BREF, Glasgow prognostic score, and pro-inflammatory cytokines.Results: All six participants, who completed the main ACCeRT study, opted to continue with compassionate use. Acceptability remained high, with overall compliance to last study/PRT visit of 81.0% for EPA, 98.8% for celecoxib, 78.9% for PRT and 77.2% for EAA. Participants continued to lose body weight and Fat-Free Mass, along with reduced albumin and increased C-Reactive protein levels. Mean time on compassionate study treatment was 78 days, and with a mean overall survival of 257 days (140 + 117).Conclusion: Non-small cell lung cancer (NSCLC) cachectic patients are willing to be enrolled onto a multi-targeted treatment regimen, and may benefit from cachexia symptom management even during their late/refractory stage.

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