Treatment of the Elderly When Cure is the Goal: The Influence of Age on Treatment Selection and Efficacy for Stage III Non-small Cell Lung Cancer

Coate, Linda; Massey, Christine; Hope, Andrew; Sacher, Adrian G.; Barrett, Katherine; Pierre, Andrew; Leighl, Natasha B.; Brade, Anthony; Perrot, Marc de; Waddell, Tom; Liu, Geoffrey; Feld, Ronald; Burkes, Ronald L.; Cho, Byoung Chul; Darling, Gail; Sun, Alexander; Keshavjee, Shaf; Bezjak, Andrea; Shepherd, Frances A.

doi:10.1097/jto.0b013e31820b8b9b

Cited by 52 publications

(31 citation statements)

References 34 publications

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“…In our study, patients with a high BMI and aged < 54.5 experienced longer PFS, which indicates that advanced age might be a negative predictive factor of chemotherapy. A previous study reported that patients aged > 65 years were more likely to have poor performance status, multiple comorbidities, and survival rates became poorer with increasing age . The shorter PFS of older patients in our study might also be a result of poor performance status and a higher rate of comorbidities, although previous research has shown that age does not worsen efficacy or tolerance to NSCLC .…”

Section: Discussioncontrasting

confidence: 55%

“…A previous study reported that patients aged > 65 years were more likely to have poor performance status, multiple comorbidities, and survival rates became poorer with increasing age. 27 The shorter PFS of older patients in our study might also be a result of poor performance status and a higher rate of comorbidities, although previous research has shown that age does not worsen efficacy or tolerance to NSCLC. 28 A larger cohort and multivariate analysis of the relationship between age and treatment efficacy are required.…”

Section: Discussionmentioning

confidence: 56%

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Influence of body mass index on the therapeutic efficacy of gemcitabine plus cisplatin and overall survival in lung squamous cell carcinoma

et al. 2018

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BackgroundGemcitabine plus cisplatin (GP) is commonly used to treat lung squamous cell carcinoma (SCC); however, it is not clear which subgroup of lung SCC patients could benefit most from GP treatment. We explored the predictive factors in lung SCC patient cohorts.MethodsSeventy‐eight lung SCC patients treated with a first‐line GP regimen were enrolled in this retrospective cohort study. Progression‐free survival (PFS) and overall survival (OS) were estimated using the Kaplan–Meier method. Classification tree models were used to explore the risk factors for PFS and OS in these patients.ResultsThe median PFS and OS in SCC patients treated with a GP regimen were 6.0 and 13.6 months, respectively. Three terminal subgroups were formed for both PFS and OS. The subgroup with a body mass index (BMI) > 23.94 kg/m2 and aged ≤ 54.5 had the longest PFS (9.0 months); the subgroup with a BMI < 23.94 kg/m2 and aged ≤ 54.5 had the shortest PFS (4.05 months). Patients with an objective response (partial or complete response) to treatment had the longest OS (20.0 months), while patients with a BMI ≤ 26.92 kg/m2 and stable or progressive disease as the best response had the shortest OS (11.2 months).ConclusionsBMI and age may be predictors of PFS in lung SCC patients who receive GP treatment. BMI and best response to GP treatment predicts OS in such patients. Patients’ clinical pathological characteristics may be used to predict the therapeutic efficacy of chemotherapy and survival.

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Section: Discussioncontrasting

confidence: 55%

Section: Discussionmentioning

confidence: 56%

Influence of body mass index on the therapeutic efficacy of gemcitabine plus cisplatin and overall survival in lung squamous cell carcinoma

et al. 2018

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“…Radiotherapy is a major therapeutic intervention for patients with lung cancer and is administered to up to 75% of lung cancer patients during the course of their disease (33). Prognosis for lung cancer patients remains poor, in part due to resistance to radiation or chemotherapy.…”

Section: Discussionmentioning

confidence: 99%

Disruption of STAT3 by Niclosamide Reverses Radioresistance of Human Lung Cancer

You

Park

et al. 2014

Molecular Cancer Therapeutics

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A major challenge affecting the outcomes of patients with lung cancer is the development of acquired radioresistance. However, the mechanisms underlying the development of resistance to therapy are not fully understood. Here we discovered that ionizing radiation (IR) induces phosphorylation of JAK2 and STAT3 in association with increased levels of Bcl2/Bcl-XL in various human lung cancer cells. To uncover new mechanism(s) of radioresistance of lung cancer, we established lung cancer cell model systems with acquired radioresistance. As compared to radiosensitive parental lung cancer cells (i.e. A549, H358 and H157), the JAK2/STAT3/Bcl2/Bcl-XL survival pathway is significantly more activated in acquired radioresistant lung cancer cells (i.e. A549-IRR, H358-IRR and H157-IRR). Higher levels of STAT3 were found to be accumulated in the nucleus of radioresistant lung cancer cells. Niclosamide, a potent STAT3 inhibitor, can reduce STAT3 nuclear localization in radioresistant lung cancer cells. Intriguingly, either inhibition of STAT3 activity by niclosamide or depletion of STAT3 by RNA interference reverses radioresistance in vitro. Niclosamide alone or in combination with radiation overcame radioresistance in lung cancer xenografts. These findings uncover a novel mechanism of radioresistance and provide a more effective approach to overcome radioresistance by blocking the STAT3/Bcl2/Bcl-XL survival signaling pathway, which may potentially improve lung cancer outcome, especially for those patients who have resistance to radiotherapy.

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“…Radiotherapy is a major therapeutic intervention for patients with lung cancer and is administered to up to 75% of lung cancer patients during the course of their disease (50). A major challenge affecting outcomes of patients with lung cancer is the development of acquired radioresistance.…”

Section: Discussionmentioning

confidence: 99%

Novel Small-Molecule Inhibitors of Bcl-XL to Treat Lung Cancer

Park

Magis

et al. 2013

Cancer Research

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Bcl-XL is a major anti-apoptotic protein in the Bcl-2 family whose overexpression is more widely observed in human lung cancer cells than that of Bcl-2, suggesting that Bcl-XL is more biologically relevant and therefore a better therapeutic target for lung cancer. Here, we screened small molecules that selectively target the BH3 domain (aa 90–98) binding pocket of Bcl-XL using the UCSF DOCK 6.1 program suite and the NCI chemical library database. We identified two new Bcl-XL inhibitors (BXI-61 and BXI-72) that exhibit selective toxicity against lung cancer cells compared with normal human bronchial epithelial cells. Fluorescence polarization assay reveals that BXI-61 and BXI-72 preferentially bind to Bcl-XL protein but not Bcl2, Bcl-w, Bfl-1/A1 or Mcl-1 in vitro with high binding affinities. Treatment of cells with BXI-72 results in disruption of Bcl-XL/Bak or Bcl-XL/Bax interaction, oligomerization of Bak and cytochrome c release from mitochondria. Importantly, BXI-61 and BXI-72 exhibit more potent efficacy against human lung cancer than ABT-737 but less degree in platelet reduction in vivo. BXI-72 overcomes acquired radioresistance of lung cancer. Based on our findings, the development of BXI(s) as a new class of anticancer agents is warranted and represents a novel strategy for improving lung cancer outcome.

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Treatment of the Elderly When Cure is the Goal: The Influence of Age on Treatment Selection and Efficacy for Stage III Non-small Cell Lung Cancer

Abstract: : In select fit elderly patients, combined modality therapy is tolerable and is associated with survival similar to that of younger patients.

Cited by 52 publications

References 34 publications

Influence of body mass index on the therapeutic efficacy of gemcitabine plus cisplatin and overall survival in lung squamous cell carcinoma

Influence of body mass index on the therapeutic efficacy of gemcitabine plus cisplatin and overall survival in lung squamous cell carcinoma

Disruption of STAT3 by Niclosamide Reverses Radioresistance of Human Lung Cancer

Novel Small-Molecule Inhibitors of Bcl-XL to Treat Lung Cancer

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