Metronomic therapy in advanced breast cancer and NSCLC: vinorelbine as a paradigm of recent progress

Abstract

Introduction: Metronomic chemotherapy (MCT) is based on frequent dosing of the drug.. This leads to pharmacologically active but low plasma concentrations that reduce toxicity. MCT seems to work primarily via indirect effects on tumor cells and their microenvironment, rather than direct antitumor effects. Oral vinorelbine is one of the most widely studied MCT approaches in both advanced breast cancer and non-small cell lung cancer. Expert opinion: MCT with vinorelbine has proven efficacy, tolerability and quality of life benefits both as monotherapy and in combination with other MCTs or targeted agents, in first-line therapy and in previously treated patients. Key populations are emerging who may be particularly well suited to metronomic vinorelbine, including those with indolent disease, older individuals, and those with multiple comorbidities and/or bone metastases. Ongoing trials should help to further delineate these target groups. Additional work is needed to better understand the optimal vinorelbine regimen, particularly when used in combination or in non-Caucasian patients. Markers are also required to help identify individuals who are most likely to respond. Nonetheless, the efficacy and tolerability of MCT, allied to improved patient convenience, reduced need for medical engagement and lower cost, make it an appealing option-particular in resource-constrained healthcare environments.

Naphthoquinone Derivatives from Angustimassarina populi CF-097565 Display Anti-Tumour Activity in 3D Cultures of Breast Cancer Cells

“…The use of NPs as anti-tumour agents against breast cancer is fully proven [ 9 , 10 , 11 ] and advanced drug discovery of new therapeutic agents in this field involves the use of well-established cell lines, cancer stem cells, spheroids or organoids that mimic the patient’s tumour. Ideally, HTS assays should be quick, simple, and easy to implement, and capable of yielding robust results, preferably at a low cost.…”

“…Indeed, during the last two decades, a handful of NPs, or NP-derivatives, have shown activity against breast cancer in vitro and in vivo [ 7 , 8 ]. As examples of the usefulness of NPs as anticancer drugs used in treatments for chemotherapy and targeted therapy against breast cancer we can find: vinorelbine (vinca alkaloid) [ 9 ], paclitaxel (taxane) [ 10 ] and/or doxorubicin (anthracyclin) [ 11 ]. Anyhow, more research is needed to bridge such encouraging pre-clinical data towards a better quality of life for the patients.…”

Phase II study of metronomic treatment with daily oral vinorelbine as first-line chemotherapy in patients with advanced/metastatic HR+/HER2− breast cancer resistant to endocrine therapy: VinoMetro—AGO-B-046

“…Taken together, there is evidence of increasing use of MCT, especially metronomic VRL, in MBC (Cazzaniga et al 2019b;Sanna et al 2020;Xu et al 2020). However, randomized trials and phase III studies are lacking and there is currently not enough evidence about which regimen and which administration should be preferred (Cardoso et al 2020;Cazzaniga et al 2019a).…”

Dose‐dependent bidirectional pharmacological effects of vinorelbine‐based metronomic combination chemotherapy on tumor growth and metastasis and mechanisms in melanoma mouse model

“…Generally, the low dose of a particular antineoplastic agent refers to a tenth to a third of MTD in MC [24]. In this study, the determination of metronomic high doses of CDDP or FU (about 1/3-1/2 MTD) in vivo was based on the MTD of CDDP or FU previously reported in preclinical studies, and the dose ratio of VNR combined CDDP or FU was determined by referring to the protocols in clinical trials [1,25,26].…”