Efficacy and Safety of Nab-Paclitaxel as Second-line Chemotherapy for Locally Advanced and Metastatic Non-small Cell Lung Cancer

Gong, Wenjing; Sun, Ping; Mu, Zhengbin; Liu, Jiannan; Yu, Caiyan; Liu, Aina

doi:10.21873/anticanres.11873

Cited by 9 publications

(8 citation statements)

References 9 publications

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“…Lung cancer is the highest mortality of all types of cancer worldwide, causing 27% of cancer deaths [ 1 ]. Taxane-based chemotherapies are used to treat approximately 70% of lung cancer patients [ 2 , 3 ]. Unfortunately, 40% of these patients recur or relapse after initial treatment as a result of acquired resistance [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

The Novel Triazolonaphthalimide Derivative LSS-11 Synergizes the Anti-Proliferative Effect of Paclitaxel via STAT3-Dependent MDR1 and MRP1 Downregulation in Chemoresistant Lung Cancer Cells

Liu

Zhang

et al. 2017

Molecules

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Multidrug resistance (MDR) is a major cause of the inefficacy and poor response to paclitaxel-based chemotherapy. The combination of conventional cytotoxic drugs has been a plausible strategy for overcoming paclitaxel resistance. Herein, we investigated the cytotoxic effects and underlying mechanism of LSS-11, a novel naphthalimide derivative-based topoisomerase inhibitor, in paclitaxel-resistant A549 (A549/T) lung cancer cells. LSS-11 enhanced cell death in A549/T cells by inducing apoptosis through increasing the DR5 protein level and PARP1 cleavage. Importantly, LSS-11 dose-dependently reduced STAT3 phosphorylation and downregulated its target genes MDR1 and MRP1, without affecting P-gp transport function. Chromatin coimmunoprecipitation (ChIP) assay further revealed that LSS-11 hindered the binding of STAT3 to the MDR1 and MRP1 promoters. Additionally, pharmacological inhibition of p-STAT3 by sulforaphane downregulated MDR1 and MRP1, resulting in A549/T cell death by triggering apoptosis. Collectively, our data show that LSS-11 is a potent naphthalimide-based chemosensitizer that could enhance cell death in paclitaxel-resistant lung cancer cells through the DR5/PARP1 pathway and STAT3/MDR1/MRP1 STAT3 inhibition.

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Section: Introductionmentioning

confidence: 99%

The Novel Triazolonaphthalimide Derivative LSS-11 Synergizes the Anti-Proliferative Effect of Paclitaxel via STAT3-Dependent MDR1 and MRP1 Downregulation in Chemoresistant Lung Cancer Cells

Liu

Zhang

et al. 2017

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“…The results showed that the ORR and DCR were 26.5% and 82.4%, respectively; the median PFS and OS were 6.0 and 11.0 months, respectively. Previous studies of nab-PTX alone in second or further line treatment of NSCLC reported a PFS of 3.5-6.6 months and an OS of 6.8-15.7 months, with ORRs ranging from 16.1%-35.5% 27 , 28 , 37 - 40 . A study of nab-PTX combined with carboplatin reported a PFS of 4.0 months and an OS of 14.0 months 41 .…”

Section: Discussionmentioning

confidence: 97%

“…This is also consistent with the known safety profiles of nab-PTX and bevacizumab 21 - 23 , 30 . Using nab-PTX alone, the rates of grade 3-4 leukopenia, neutropenia, and anemia have been reported to be 5%-49%, 2%-69%, and 0%-32% 24 , 27 , 28 , 37 - 40 . In a study of nab-PTX combined with carboplatin, neutropenia, thrombocytopenia, and anemia were observed in 28.0%, 12.0%, and 8.0% of the patients, respectively 41 .…”

Section: Discussionmentioning

confidence: 99%

“…In China, nab-PTX is mostly used as the second or further line treatment option because of limitations in indications, medical insurance, and costs, among others. A few studies reported that nab-PTX as a second or further line chemotherapy regimen was effective in advanced NSCLC in Western and East Asian populations 27 - 29 . Nevertheless, there is no consensus or standardized protocol for the second or further line use of nab-PTX in patients with advanced NSCLC, and the exact effectiveness and safety data of nab-PTX in unknown.…”

Section: Introductionmentioning

confidence: 99%

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Nab-paclitaxel in combination with Bevacizumab in patients with non-squamous non-small cell lung cancer after failure of at least one prior systemic regimen

Hao

Zhu

et al. 2020

J. Cancer

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Background: Most patients with non-small cell lung cancer (NSCLC) experience disease progression after first-line treatment. The efficacy and safety of the nab-paclitaxel (nab-PTX) and bevacizumab combination as the second or further line of treatment in patients with advanced NSCLC have not been reported yet. Objective: To evaluate the efficacy and safety of the nab-PTX and bevacizumab combination in patients with advanced non-squamous (NSQ) NSCLC after failure of at least one prior systemic regimen. Methods: Patients with advanced (stage IV) NSQ NSCLC who received the nab-PTX and bevacizumab combination as the second or further line treatment between February 2012 and December 2018 at the Cancer Hospital of the Chinese Academy of Medical Sciences (Beijing, China) were included in this retrospective study. The main outcomes included the objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and safety. Results: Thirty-four patients received 1-27 cycles (median, four cycles) of treatment; 67.6% (23/34) patients had undergone at least two lines of previous treatment. The ORR and disease control rates were 26.5% (9/34) and 82.4% (28/34), respectively. The median PFS and OS were 6.0 (95% CI=2.9-7.2) and 11.0 (95% CI=7.8-18.7) months, respectively. The multivariable analyses indicated that the combined use of other drugs and pleural metastasis were respectively associated with better PFS (hazard ratio=0.354, 95% CI=0.134-0.935, P=0.036) and OS (hazard ratio=0.540, 95% CI=0.118-0.980, P=0.046). The most frequent grade 3-4 adverse events (AEs) were neutropenia 20.6% (7/34), leukopenia 8.8% (3/34), and anemia 5.9% (2/34). No grade 5 AE occurred. Conclusion: Combined nab-PTX and bevacizumab might be an effective treatment regimen for patients with advanced NSQ NSCLC after failure of at least one prior systemic regimen, but studies have to validate those findings.

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“…That result was inspiring since the basic treatment options for SCC at the time were limited[9]. Several studies have also demonstrated the efficacy and tolerability of nab-PC as second-line or late-phase chemotherapy in advanced SCC[10-14]. For our patient, nab-PC plus cisplatin was first administered as the second-line therapy, due to the patient’s poor response to the DP therapy; it showed consid-erable efficacy and led to a total PFS of 23.9-mo, without obvious adverse effects.…”

Section: Discussionmentioning

confidence: 99%

Multiline treatment of advanced squamous cell carcinoma of the lung: A case report and review of the literature

Yang

Peng

Zhang

2019

WJCC

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BACKGROUND Squamous cell carcinoma (SCC) is one the most common subtypes of non-small cell lung cancer, yet the treatment options for it remain limited. Here, we report a case of advanced SCC and review the related literature focusing on the multiline therapy method. CASE SUMMARY We report the case of a 45-year-old man with advanced SCC who was deemed inoperable at the time of advanced SCC diagnosis. The patient had been referred to our hospital in April 2013 with complaints of a stuffy feeling in the chest, dyspnea, and pain in the right shoulder lasting for 1 mo. Physical examination found no obvious abnormalities, except for lower breath sound in the right lower lung. Laboratory data were within normal limits. Immunohistochemistry analysis of the tumor tissue showed CK5/6 (+), p63 (+), CD56 (+), and Ki-67 (+, approximately 30%), and genetic testing detected no EGFR mutation. He received a multiline treatment that included chemotherapy, radiotherapy, targeted therapy, and antiangiogenic therapy. After more than 5-year comprehensive treatment, the patient remains alive. CONCLUSION This typical case highlights the importance of appropriate multiline therapy for those patients with advanced SCC.

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Efficacy and Safety of Nab-Paclitaxel as Second-line Chemotherapy for Locally Advanced and Metastatic Non-small Cell Lung Cancer

Abstract: Nab-paclitaxel is an effective chemotherapy for locally advanced and metastatic NSCLC as treatment and has a superior application prospect for squamous NSCLC. Toxicity is generally mild and manageable.

Cited by 9 publications

References 9 publications

The Novel Triazolonaphthalimide Derivative LSS-11 Synergizes the Anti-Proliferative Effect of Paclitaxel via STAT3-Dependent MDR1 and MRP1 Downregulation in Chemoresistant Lung Cancer Cells

The Novel Triazolonaphthalimide Derivative LSS-11 Synergizes the Anti-Proliferative Effect of Paclitaxel via STAT3-Dependent MDR1 and MRP1 Downregulation in Chemoresistant Lung Cancer Cells

Nab-paclitaxel in combination with Bevacizumab in patients with non-squamous non-small cell lung cancer after failure of at least one prior systemic regimen

Multiline treatment of advanced squamous cell carcinoma of the lung: A case report and review of the literature

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