Safety of First-line Chemotherapy with Metronomic Single-agent Oral Vinorelbine in Elderly Patients with NSCLC

Filiberti, Rosa Angela; Taveggia, Paola; Corso, Lisette Del; Conte, Alessandro Del; Covesnon, Maria Grazia; Puccetti, C.; Donati, Sara; Auriati, Laura; Amoroso, Domenico; Camerini, Andrea

doi:10.21873/anticanres.11679

Cited by 11 publications

(14 citation statements)

References 26 publications

(43 reference statements)

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“…Vinorelbine is as an oral formulation and that is convenient to be taken. Previous studies have shown that metronomic oral vinorelbine alone can be safely used in elderly patients with advanced NSCLC [ 4 , 5 ]. But in the present study, we investigated the impact of MET NVB and/or Endostar on the frequency of CEPs, expression of CD31, VEGF, and HIF-1α in tumor-bearing mice.…”

Section: Discussionmentioning

confidence: 99%

“…Tumor growth and metastasis by antagonizing angiogenesis are also inhibited [ 3 ]. Previous studies have shown that metronomic oral Vinorelbine can be safely used in elderly patients with advanced NSCLC, allowing for long-term disease stabilization combined with optimal patient compliance [ 4 , 5 ]. Together, these studies, including numerous preclinical and clinical trials, provide accumulative evidence that MET maintains the therapeutic response, minimizes relapse after conventional chemotherapy, and overcomes resistance [ 1 – 3 ].…”

Section: Introductionmentioning

confidence: 99%

“…Vinorelbine binds to tubulin, thereby preventing formation of the mitotic spindle, which leads to cell death [ 8 ]. Vinorelbine is a semisynthetic vinca alkaloid and, as an oral formulation, is favored in the chronic administration protocol of MET [ 4 , 5 , 9 ]. Given this major advantage and necessity when using oral chemotherapy drugs in the clinic or in preclinical MET treatment approaches [ 4 , 5 ], Vinorelbine was chosen as the prime candidate in this study.…”

Section: Introductionmentioning

confidence: 99%

“…Vinorelbine is a semisynthetic vinca alkaloid and, as an oral formulation, is favored in the chronic administration protocol of MET [ 4 , 5 , 9 ]. Given this major advantage and necessity when using oral chemotherapy drugs in the clinic or in preclinical MET treatment approaches [ 4 , 5 ], Vinorelbine was chosen as the prime candidate in this study. Several studies have reported that anti-angiogenic drugs combined with metronomic chemotherapy is used in for the treatment of advanced NSCLC and being investigated in various types of cancer, including cancer of the prostate and breast [ 10 – 12 ].…”

Section: Introductionmentioning

confidence: 99%

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Enhanced antitumor and anti-angiogenic effects of metronomic Vinorelbine combined with Endostar on Lewis lung carcinoma

Qin¹,

Zhang

Zhu

et al. 2018

BMC Cancer

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BackgroundConventional chemotherapy is commonly used to treat non-small cell lung cancer (NSCLC) however it increases therapeutic resistance. In contrast, metronomic chemotherapy (MET) is based on frequent drug administration at lower doses, resulting in inhibition of neovascularization and induction of tumor dormancy. This study aims to evaluate the inhibitory effects, adverse events, and potential mechanisms of MET Vinorelbine (NVB) combined with an angiogenesis inhibitor (Endostar).MethodsCirculating endothelial progenitor cells (CEPs), apoptosis rate, expression of CD31, vascular endothelial growth factor (VEGF), hypoxia inducible factor-1 (HIF-1α) were determined using flow cytometry, western blot analysis, immunofluorescence staining and Enzyme-linked immunosorbent assay (ELISA) analysis. And some animals were also observed using micro fluorine-18-deoxyglucose PET/computed tomography (18F-FDG PET/CT) to identify changes by comparing SUVmax values. In addition, white blood cell (WBC) counts and H&E-stained sections of liver, lungs, kidney, and heart were performed in order to monitor toxicity assessments.ResultsWe found that treatment with MET NVB + Endo was most effective in inhibiting tumor growth, decreasing expression of CD31, VEGF, HIF-1α, and CEPs, and reducing side effects, inducing apoptosis, such as expression of Bcl-2, Bax and caspase-3. Administration with a maximum tolerated dose of NVB combined with Endostar (MTD NVB + Endo) demonstrated similar anti-tumor effects, including changes in glucose metabolism with micro fluorine-18-deoxyglucose PET/computed tomography (18F-FDG PET/CT) imaging, however angiogenesis was not inhibited. Compared with either agent alone, the combination of drugs resulted in better anti-tumor effects.ConclusionThese results indicated that MET NVB combined with Endo significantly enhanced anti-tumor and anti-angiogenic responses without overt toxicity in a xenograft model of human lung cancer.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Enhanced antitumor and anti-angiogenic effects of metronomic Vinorelbine combined with Endostar on Lewis lung carcinoma

Qin¹,

Zhang

Zhu

et al. 2018

BMC Cancer

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“…Platinum-based chemotherapy is most commonly used in patients with advanced or recurrent NSCLC and ED-SCLC (Extensive Disease Small Cell Lung Cancer) 3 , 6 , 7 . However, the long-term benefit of first-line chemotherapy is limited, and some studies showed that median overall survival was only 8 months in patients with advanced NSCLC patients, and only 9 months in the patients with ED-SCLC 8 , 9 . In recent years, biological agents, such as bevacizumab and cetuximab, among others, have been added to chemotherapy regimens.…”

Section: Introductionmentioning

confidence: 99%

Efficacy and Safety of Ipilimumab plus Chemotherapy for Advanced Lung Cancer: A Systematic Review and Meta-Analysis

Zhang

Shen

et al. 2018

J. Cancer

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Lung cancer is the leading cause of cancer-related deaths worldwide, with poor prognosis in advanced lung cancer patients. Platinum-based chemotherapy has always been a first-line treatment for the majority of advanced lung cancer patients, but its long-term survival benefit is limited. Ipilimumab is an immune drug that targets the CTLA-4 protein in T cells. Therefore, we evaluated the efficacy and safety of adding ipilimumab to simple chemotherapy for patients with advanced lung cancer. We searched literatures in PubMed, Web of Science, EMBASE, the Cochrane Library and cliniclatrials.gov. The primary end points of this assessment were overall survival (OS), progression-free survival (PFS) and immune-related PFS(irPFS) of lung cancer patients. Other end points were objective response rate (ORR), disease control rate (DCR) and safety. The results of this study will be presented by the risk ratio (RR) of the endpoints and the 95% confidence interval (CI) of the various effect sizes. And when the p value is less than 0.05, we think there is a statistical difference. Finally, 6 RCTs and 2,037 patients including 953 with advanced or recurrent non-small cell lung cancer (NSCLC) and 1084 with extensive-disease small-cell lung cancer (ED-SCLC) were identified. Among them, 1089 received immunochemotherapy, and 948 patients received chemotherapy alone. Immunochemotherapy can't improve OS (6months: risk ratio (RR)=0.97 P=0.11; 1year: RR=1.05 P=0.36), ORR (RR=1.00 P=0.95) and DCR (RR=0.92, 95%CI 0.85-1.00, P=0.04) of patients with lung cancer compared to pure chemotherapy, but it can improve the PFS (6months: RR=1.16 P=0.02; 1year: RR=1.39 P=0.02) and 6months-irPFS(RR=1.60 P=0.004). However, due to the addition of ipilimumab, the immune-related toxicities are more apparent in immunochemotherapy group.

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Vinorelbine in bladder-preserving multimodality treatment for muscle-invasive bladder cancer—a valid option for cisplatin-unfit patients?

et al. 2021

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Purpose Treatment of muscle-invasive bladder cancer (MIBC) remains challenging, especially for elderly and/or comorbid patients. Patients who are unfit for or refuse surgery should receive bladder-preserving multimodality treatment (BPMT), consisting of transurethral resection of the bladder tumor (TURB) followed by combined chemoradiotherapy (CRT). We aimed to investigate the effectiveness of vinorelbine, a chemotherapeutic agent not routinely used for MIBC, in patients referred to CRT who are unfit for standard chemotherapy and would thus rely solely on radiotherapy (RT). Methods We retrospectively analyzed 52 consecutive patients with MIBC who received standard CRT with cisplatin (n = 14), CRT with vinorelbine (n = 26), or RT alone (n = 12). Primary endpoints were median overall survival (OS) and median cancer-specific survival (CSS). Secondary endpoints were median local control (LC), median distant control (DC), and OS, CSS, LC, and DC after 1, 2, and 3 years, respectively. Results Median OS and CSS were significantly higher for patients who received vinorelbine as compared to RT alone (OS 8 vs. 22 months, p = 0.003; CSS 11 months vs. not reached, p = 0.001). Median LC and DC did not differ significantly between groups. Vinorelbine was well tolerated with no reported side effects >grade II. Conclusion Our results suggest that CRT with vinorelbine is well tolerated and superior to RT alone in terms of OS and CSS. Therefore, this treatment regime might constitute a new treatment option for patients with MIBC who are unfit for or refuse surgery or standard chemotherapy. This study encourages a randomized controlled trial to compare this new regime to current standard therapies.

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Safety of First-line Chemotherapy with Metronomic Single-agent Oral Vinorelbine in Elderly Patients with NSCLC

Abstract: Metronomic oral vinorelbine is safe in elderly patients, allowing for long-term disease stabilization with optimal patient compliance.

Cited by 11 publications

References 26 publications

Enhanced antitumor and anti-angiogenic effects of metronomic Vinorelbine combined with Endostar on Lewis lung carcinoma

Enhanced antitumor and anti-angiogenic effects of metronomic Vinorelbine combined with Endostar on Lewis lung carcinoma

Efficacy and Safety of Ipilimumab plus Chemotherapy for Advanced Lung Cancer: A Systematic Review and Meta-Analysis

Vinorelbine in bladder-preserving multimodality treatment for muscle-invasive bladder cancer—a valid option for cisplatin-unfit patients?

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