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Cancer Communications (London, England) Oct 2022
Topics: Administration, Metronomic; Humans; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms; Xenograft Model Antitumor Assays
PubMed: 35924896
DOI: 10.1002/cac2.12347 -
Indian Journal of Cancer 2013Cytotoxic antiproliferative chemotherapeutic agents are the mainstay of treatment in cancers. Chemotherapy is usually administered every 2-3 weeks. Along with acute... (Review)
Review
Cytotoxic antiproliferative chemotherapeutic agents are the mainstay of treatment in cancers. Chemotherapy is usually administered every 2-3 weeks. Along with acute toxicity and long-term effects of cumulative doses, this strategy potentially allows regrowth of the tumor in the interval period and leads to the emergence of resistant populations of tumor cells. Moreover, even with intense chemotherapy, the outcome is stagnating for most of the tumors. There has been recent interest in the use of chemotherapy in fractionated doses which is far below the maximum tolerated dose. This is called metronomic scheduling of chemotherapy. Here, we review the biology and evidence for metronomic chemotherapy.
Topics: Administration, Metronomic; Angiogenesis Inhibitors; Antineoplastic Combined Chemotherapy Protocols; Humans; Neoplasms; Neovascularization, Pathologic
PubMed: 23979206
DOI: 10.4103/0019-509X.117027 -
Oncology 2016Locally advanced oral cavity cancers are treated with a multi-modality approach. Surgery is the most efficient local modality in comparison to chemoradiation in oral... (Review)
Review
Locally advanced oral cavity cancers are treated with a multi-modality approach. Surgery is the most efficient local modality in comparison to chemoradiation in oral cancers. Preoperative chemotherapy has failed its expectations to improve disease-free survival or overall survival in resectable oral cancers. Its use as an organ preservation tool is being studied. Induction chemotherapy followed by assessment for surgery is an appropriate option for borderline resectable or technically unresectable oral cancer. Metronomic chemotherapy is being studied as a bridge to surgery and as adjuvant chemotherapy in locally advanced oral cancers. The role of induction chemotherapy in unresectable oral cancers is unproven. Metronomic chemotherapy has shown improved progression-free survival and overall survival in oral cancers in comparison to intravenous cisplatin. A phase 3 study for confirmation of this finding has begun.
Topics: Administration, Metronomic; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Docetaxel; Fluorouracil; Humans; Induction Chemotherapy; Mouth Neoplasms; Neoadjuvant Therapy; Preoperative Care; Taxoids
PubMed: 27463093
DOI: 10.1159/000447579 -
Cancer Letters Aug 2017Therapeutic resistance is amongst the major determinants of cancer mortality. Contrary to initial expectations, antivascular therapies are equally prone to inherent or... (Review)
Review
Therapeutic resistance is amongst the major determinants of cancer mortality. Contrary to initial expectations, antivascular therapies are equally prone to inherent or acquired resistance as other cancer treatment modalities. However, studies into resistance to vascular endothelial growth factor pathway inhibitors revealed distinct mechanisms of resistance compared to conventional cytotoxic therapy. While some of these novel mechanisms of resistance also appear to be functional regarding metronomic chemotherapy, herein we summarize available evidence for mechanisms of resistance specifically described in the context of metronomic chemotherapy. Numerous preclinically identified molecular targets and pathways represent promising avenues to overcome resistance and enhance the benefits achieved with metronomic chemotherapy eventually. However, there are considerable challenges to clinically translate the preclinical findings.
Topics: Administration, Metronomic; Angiogenesis Inhibitors; Animals; Antineoplastic Combined Chemotherapy Protocols; Drug Resistance, Neoplasm; Endothelial Cells; Humans; Molecular Targeted Therapy; Neoplasms; Neoplastic Stem Cells; Neovascularization, Pathologic; Signal Transduction
PubMed: 28259819
DOI: 10.1016/j.canlet.2017.02.027 -
Oncology Letters Dec 2020Metronomic chemotherapy (MCT) is defined as the rhythmic chemotherapy of low-dose cytotoxic drugs with short or no drug-free breaks over prolonged periods. MCT affects... (Review)
Review
Metronomic chemotherapy (MCT) is defined as the rhythmic chemotherapy of low-dose cytotoxic drugs with short or no drug-free breaks over prolonged periods. MCT affects tumor cells and the tumor microenvironment. Particularly, the low-dose schedule impairs the repair process of endothelial cells, resulting in an anti-angiogenesis effect. By stimulating the immune system to eliminate tumor cells, MCT induces immunological activation. Furthermore, combined with targeted therapy, anti-angiogenic drugs enhance the efficacy of MCT. The present review is an overview of phase I, II and III clinical trials focusing on the efficacy, toxicity and mechanism of MCT in patients with non-small cell lung cancer (NSCLC). Furthermore, the prospects of MCT in NSCLC have been discussed. The present review indicated that MCT is an efficacious treatment for selected patients with NSCLC, with acceptable systemic side effects and economic viability for public health.
PubMed: 33093916
DOI: 10.3892/ol.2020.12170 -
Cancer Letters Apr 2018Conventional cytotoxic cancer chemotherapy is often immunosuppressive and associated with drug resistance and tumor regrowth after a short period of tumor shrinkage or... (Review)
Review
Conventional cytotoxic cancer chemotherapy is often immunosuppressive and associated with drug resistance and tumor regrowth after a short period of tumor shrinkage or growth stasis. However, certain cytotoxic cancer chemotherapeutic drugs, including doxorubicin, mitoxantrone, and cyclophosphamide, can kill tumor cells by an immunogenic cell death pathway, which activates robust innate and adaptive anti-tumor immune responses and has the potential to greatly increase the efficacy of chemotherapy. Here, we review studies on chemotherapeutic drug-induced immunogenic cell death, focusing on how the choice of a conventional cytotoxic agent and its dose and schedule impact anti-tumor immune responses. We propose a strategy for effective immunogenic chemotherapy that employs a modified metronomic schedule for drug delivery, which we term medium-dose intermittent chemotherapy (MEDIC). Striking responses have been seen in preclinical cancer models using MEDIC, where an immunogenic cancer chemotherapeutic agent is administered intermittently and at an intermediate dose, designed to impart strong and repeated cytotoxic damage to tumors, and on a schedule compatible with activation of a sustained anti-tumor immune response, thereby maximizing anti-cancer activity. We also discuss strategies for combination chemo-immunotherapy, and we outline approaches to identify new immunogenic chemotherapeutic agents for drug development.
Topics: Administration, Metronomic; Animals; Antineoplastic Agents; Cell Survival; Combined Modality Therapy; Dose-Response Relationship, Drug; Humans; Immunotherapy; Neoplasms; Xenograft Model Antitumor Assays
PubMed: 29414305
DOI: 10.1016/j.canlet.2018.01.050 -
Journal of Cancer Research and Clinical... Aug 2021Chemotherapy remains a widely used cancer treatment. Acquired drug resistance may greatly reduce the efficacy of treatment and means to overcome it are a topic of active...
Chemotherapy remains a widely used cancer treatment. Acquired drug resistance may greatly reduce the efficacy of treatment and means to overcome it are a topic of active discussion among researchers. One of the proposed solutions is to shift the therapeutic paradigm from complete eradication of cancer to maintenance, i.e., to treat it as a chronic disease. A concept of metronomic therapy (low chemotherapy doses applied continuously) emerged in early 2000s and was henceforth shown to offer a number of benefits, including targeting endothelial cells and reducing acquired drug resistance. Using mathematical modeling and optimal control techniques, we investigate the hypothesis that lower doses of chemotherapy are beneficial for patients. Our analysis of a mathematical model of tumor growth under angiogenic signaling proposed by Hahnfeldt et al. adapted to heterogeneous tumors treated by combined anti-angiogenic agent and chemotherapy offers insights into the effects of metronomic therapy. Firstly, assuming constant long-term drug delivery, the model suggests that the longest survival time is achieved for intermediate drug doses. Secondly, by formalizing the notion of the therapeutic target being maintenance rather than eradication, we show that in the short term, optimal chemotherapy scheduling consists mainly of a drug applied at a low dose. In conclusion, we suggest that metronomic therapy is an attractive alternative to maximum tolerated dose therapies to be investigated in experimental settings and clinical trials.
Topics: Angiogenesis Inhibitors; Antineoplastic Combined Chemotherapy Protocols; Calibration; Drug Administration Schedule; Drug Resistance, Neoplasm; Humans; Models, Theoretical; Neoplasms; Neovascularization, Pathologic; Survival Analysis; Time Factors
PubMed: 34050795
DOI: 10.1007/s00432-021-03657-9 -
Future Oncology (London, England) Jul 2022This is an open-label, single-center, multi-cohort phase Ib trial, which consists of three cohorts, including cohort 1 (HER2 negative gastric or gastric esophageal... (Review)
Review
This is an open-label, single-center, multi-cohort phase Ib trial, which consists of three cohorts, including cohort 1 (HER2 negative gastric or gastric esophageal junction adenocarcinoma), cohort 2 (esophageal squamous cell carcinoma and head and neck squamous cell carcinoma) and cohort 3 (hepato-biliary-pancreatic and non-stomach non-esophagi gastrointestinal carcinoma). All eligible patients will be treated by camrelizumab (200 mg, every 2 weeks) and capecitabine (500 mg, twice a day, ). The primary end point is the safety profiles of camrelizumab plus metronomic capecitabine according to CTCAE v5.0. The secondary end points are progression free survival, overall survival, objective response rate, disease control rate and duration of response. Planned enrollment is 20 subjects for each cohort. Total duration of this trial is expected to be 2 years.
Topics: Adenocarcinoma; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Capecitabine; Clinical Trials, Phase I as Topic; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Humans; Neoplasms; Stomach Neoplasms
PubMed: 35703115
DOI: 10.2217/fon-2021-1579 -
Heliyon Feb 2024Cancer represents a significant global health and economic burden due to its high mortality rates. While effective in some instances, traditional chemotherapy often... (Review)
Review
Cancer represents a significant global health and economic burden due to its high mortality rates. While effective in some instances, traditional chemotherapy often falls short of entirely eradicating various types of cancer. It can cause severe side effects due to harm to healthy cells. Two therapeutic approaches have risen to the forefront to address these limitations: metronomic chemotherapy (MCT) and drug repurposing. Metronomic chemotherapy is an innovative approach that breaks from traditional models. It involves the administration of chemotherapeutic regimens at lower doses, without long drug-free intervals that have previously been a hallmark of such treatments. This method offers a significant reduction in side effects and improved disease management. Simultaneously, drug repurposing has gained considerable attraction in cancer treatment. This approach involves utilizing existing drugs, initially developed for other therapeutic purposes, as potential cancer treatments. The application of known drugs in a new context accelerates the timeline from laboratory to patient due to pre-existing safety and dosage data. The intersection of these two strategies gives rise to a novel therapeutic approach named 'Metronomics.' This approach encapsulates the benefits of both MCT and drug repurposing, leading to reduced toxicity, potential for oral administration, improved patient quality of life, accelerated clinical implementation, and enhanced affordability. Numerous clinical studies have endorsed the efficacy of metronomic chemotherapy with tolerable side effects, underlining the potential of Metronomics in better cancer management, particularly in low- and middle-income countries. This review underscores the benefits and applications of metronomic chemotherapy and drug repurposing, specifically in the context of breast cancer, showcasing the promising results of pre-clinical and clinical studies. However, we acknowledge the necessity of additional clinical investigations to definitively establish the role of metronomic chemotherapy in conjunction with other treatments in comprehensive cancer management.
PubMed: 38314272
DOI: 10.1016/j.heliyon.2024.e24670 -
OncoTargets and Therapy 2019The prognosis for patients with locally advanced or metastatic breast cancer (mBC) remains poor, with a median survival of 2-4 years. About 10% of newly diagnosed breast...
The prognosis for patients with locally advanced or metastatic breast cancer (mBC) remains poor, with a median survival of 2-4 years. About 10% of newly diagnosed breast cancer patients present with metastatic disease, and 30%-50% of those diagnosed at earlier stages will subsequently progress to mBC. In terms of ongoing management for advanced/metastatic breast cancer after failure of hormonal therapy, there is a high medical need for new treatment options that prolong the interval to the start of intensive cytotoxic therapy, which is often associated with potentially serious side effects and reduced quality of life. Oral chemotherapeutic agents such as capecitabine and vinorelbine have demonstrated efficacy in patients with mBC, with prolonged disease control and good tolerability. Use of oral chemotherapy reduces the time and cost associated with treatment and is often more acceptable to patients than intravenous drug delivery. Metronomic administration of oral chemotherapy is therefore a promising treatment strategy for some patients with mBC and inhibits tumor progression via multiple mechanisms of action. Ongoing clinical trials are investigating metronomic chemotherapy regimens as a strategy to prolong disease control with favorable tolerability. This article provides an overview of metronomic chemotherapy treatment options in mBC, with perspectives on this therapy from a panel of experts.
PubMed: 31114242
DOI: 10.2147/OTT.S189163