Vinorelbine

BackgroundCisplatin-based chemoradiotherapy is the standard treatment for unresectable, locally advanced non-small-cell lung cancer (NSCLC). This trial evaluated two experimental regimens that combine chemotherapy with concurrent radiotherapy.MethodsEligible patients with unresectable stage III NSCLC were randomised to either the SP arm (S-1 and cisplatin) or VP arm (vinorelbine and cisplatin), with early concurrent thoracic radiotherapy of 60 Gy, comprising 2 Gy per daily fraction. The primary endpoint was the overall survival rate at 2 years (2-year overall survival (OS)) (Study ID: UMIN000002420).ResultsFrom September 2009 to September 2012, 112 patients were enroled. Of the 108 eligible patients, the 2-year OS was 75.6% (80% confidence interval (CI), 67-82%) in the SP arm and 68.5% (80% CI: 60-76%) in the VP arm. The hazard ratio (HR) for death between the two arms was 0.85 (0.48-1.49). The median progression-free survival was 14.8 months for the SP arm and 12.3 months for the VP arm with an HR of 0.92 (0.58-1.44). There were four treatment-related deaths in the SP arm and five in the VP arm.ConclusionsThe null hypotheses for 2-year OS were rejected in both arms. The West Japan Oncology Group will employ the SP arm as the investigational arm in a future phase III study.

BackgroundThe biological effect of oral metronomic vinorelbine (mVNB) alone or in combination with endocrine therapy in patients with hormone receptor-positive (HR+)/HER2-negative breast cancer has been scarcely addressed.MethodsPostmenopausal women with untreated stage I-III HR+/HER2-negative breast cancer were randomized (1:1:1) to receive 3 weeks of letrozole (LTZ) 2.5 mg/day, oral mVNB 50 mg 3 days/week, or the combination. The primary objective was to evaluate, within PAM50 Luminal A/B disease, if the anti-proliferative effect of LTZ+mVNB was superior to monotherapy. An anti-proliferative effect was defined as the mean relative decrease of the PAM50 11-gene proliferation score in combination arm vs. both monotherapy arms. Secondary objectives included the evaluation of a comprehensive panel of breast cancer-related genes and safety. An unplanned analysis of stromal tumor-infiltrating lymphocytes (sTILs) was also performed. PAM50 analyses were performed using the nCounter®-based Breast Cancer 360™ gene panel, which includes 752 genes and 32 signatures.ResultsSixty-one patients were randomized, and 54 paired samples (89%) were analyzed. The main patient characteristics were mean age of 67, mean tumor size of 1.7 cm, mean Ki67 of 14.3%, stage I (55.7%), and grades 1-2 (90%). Most baseline samples were PAM50 Luminal A (74.1%) or B (22.2%). The anti-proliferative effect of 3 weeks of LTZ+mVNB (- 73.2%) was superior to both monotherapy arms combined (- 49.9%; p = 0.001) and mVNB (- 19.1%; p ConclusionsShort-term mVNB is well-tolerated and presents anti-proliferative activity alone and in combination with LTZ. The high expression of immune-related biological processes and sTILs observed with the combination opens the possibility of studying this combination with immunotherapy. Further investigation comparing these biological results with other metronomic schedules or drug combinations is warranted.Trial registrationNCT02802748 , registered 16 June 2016.

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.

Lung cancer remains one of the most frequently diagnosed malignancies and the leading cause of cancer-related mortality globally. Metronomic chemotherapy (MC) enables prolonged low-dose treatment administration with lower toxicity while maintaining therapeutic efficacy. Our goal was to assess the efficacy and safety of oral vinorelbine (OV) administered in a metronomic schedule in elderly patients with locally advanced or metastatic non-small cell lung cancer (NSCLC). Patients & methods This single-center study was conducted at the Clinical Oncology Department of Suez Canal University Hospital. The study included elderly patients (aged ≥ 60 years) with locally advanced or metastatic NSCLC (TNM stage IIIB/IV) who had previously received first-line platinum-based chemotherapy with or without concomitant chemoradiotherapy. All patients were confirmed to lack sensitizing EGFR mutations as well as ALK and ROS1 rearrangements, irrespective of PD-L1 expression status and were treated between January 2020 and October 2024. The study population consisted of histopathologically-proven patients who fulfilled the inclusion and exclusion criteria. Patients received metronomic OV at fixed doses (30, 40, or 50 mg three times weekly) until disease progression or development of unacceptable toxicity. Results From January 2020 to October 2024, 50 patients were included: 39 men (78%) and 11 women (11%). The median age was 67 years. The predominant histological subtype was squamous cell carcinoma (44%). The duration of OV therapy ranged from 6 to 18 months, with a mean of 9.16 ± 3.6 months. Patients received 8 to 24 cycles, with a mean of 11.74 ± 4.44. According to RECIST criteria, the disease control rate was 78% after 6 months, while the overall response rate was 64%. No grade 4 or 5 adverse events were observed. The mean progression-free survival (PFS) was 13.74 months (95% CI: 12.11 to 15.36), whereas the mean overall survival (OS) was 19.67 months (95% CI: 17.85 to 21.49). Comparison of EORTC QLQ-C30 quality-of-life (QoL) scores before treatment and after 6 months of OV therapy demonstrated improvement in patients' functioning and QoL. Conclusion Metronomic OV demonstrated clinical efficacy in elderly patients with advanced wild-type NSCLC. It was associated with a significant reduction in toxicity and may represent a valuable therapeutic option for this age group, with excellent treatment compliance.