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Cancer Letters Apr 2024Metronomic chemotherapy refers to the consistent and regular administration of low-dose chemotherapeutic agents over an extended period, with minimal or no extended... (Review)
Review
Metronomic chemotherapy refers to the consistent and regular administration of low-dose chemotherapeutic agents over an extended period, with minimal or no extended drug-free intervals. The effectiveness of metronomic chemotherapy is derived from its capacity to impede tumor angiogenesis and foster antitumor immune responses, rather than merely interrupting tumor cell mitosis. Metronomic chemotherapy has been applied in the treatment of neuroblastoma for decades, including patients with newly diagnosed high-risk neuroblastoma and relapsed or refractory neuroblastoma. In the modern era of neuroblastoma treatment, metronomic chemotherapy remains a viable option for maintenance therapy in newly diagnosed neuroblastoma patients without access to autologous stem cell transplantation or immunotherapy, especially in resource-limited regions. For relapsed or refractory patients, metronomic chemotherapy is a suitable alternative for individuals intolerant to intensified treatments or receiving palliative care. Cyclophosphamide, etoposide, vinca alkaloids, and celecoxib constitute the primary components of current metronomic chemotherapy. Given the need for additional research to determine the optimal regimen, comprehensive studies must be conducted to explore and establish standardized metronomic chemotherapy protocols. Additionally, investigating potential biomarkers and clinical prognostic factors is imperative for future advancements in this field.
Topics: Humans; Hematopoietic Stem Cell Transplantation; Antineoplastic Combined Chemotherapy Protocols; Transplantation, Autologous; Neuroblastoma; Cyclophosphamide; Administration, Metronomic
PubMed: 38311055
DOI: 10.1016/j.canlet.2024.216617 -
Cancer Letters Nov 2014Chemotherapy is the mainstay of treatment in mid-advanced tumors. Considering their toxicity on hematopoietic cells, chemotherapeutics are often considered as... (Review)
Review
Chemotherapy is the mainstay of treatment in mid-advanced tumors. Considering their toxicity on hematopoietic cells, chemotherapeutics are often considered as immunosuppressive inducers. However, recently accumulating data indicate that some chemotherapeutic agents with specific administration schedules also display some positive immunological effect to contribute to tumor elimination. For instance, metronomic chemotherapy could promote tumor eradication not only by inhibiting tumor angiogenesis but also by selectively eliminating immunosuppressive cells and improving anti-tumor immune responses. In this review, we summarize what is currently known regarding metronomic chemotherapy-induced immunoregulation. Understanding of the molecular mechanisms of metronomic chemotherapy-induced immunoregulation may yield invaluable information for the optimal design of immunochemotherapies.
Topics: Administration, Metronomic; Animals; Antineoplastic Agents; Humans; Immunomodulation; Neoplasms
PubMed: 25168479
DOI: 10.1016/j.canlet.2014.08.028 -
Zhongguo Fei Ai Za Zhi = Chinese... Apr 2015Metronomic chemotherapy is an emerging strategy to fight cancer. Unlike traditional chemotherapy, metronomic chemotherapy is defined by the frequent, repetitive... (Review)
Review
Metronomic chemotherapy is an emerging strategy to fight cancer. Unlike traditional chemotherapy, metronomic chemotherapy is defined by the frequent, repetitive administration of chemotherapeutic drugs at relatively low doses, and without prolonged drug-free break. Initially thought to play a role inhibiting tumor angiogenesis by targeting activated endothelial cells in tumors, metronomic chemotherapy is a multi-targeted therapy,including activation of immunity, effect on tumour initiating cells, induction of tumor dormancy. It is from eradicateing tumor cells to improve effect, reduce the toxicity and improve quality of life for treatment of advanced non-small cell lung cancer (NSCLC). Metronomic chemotherapy which can avoid the toxicity of traditional chemotherapy and rebounding is explored in clinical studies of advanced NSCLC, as a promising treatment strategy.
Topics: Administration, Metronomic; Animals; Antineoplastic Agents; Carcinoma, Non-Small-Cell Lung; Humans; Lung Neoplasms
PubMed: 25936888
DOI: 10.3779/j.issn.1009-3419.2015.04.08 -
Cancer Letters Jun 2024Metronomic chemotherapy (mCHEMO), based on frequent, regular administration of low, but pharmacologically active drug doses, optimizes antitumor efficacy by targeting... (Review)
Review
Metronomic chemotherapy (mCHEMO), based on frequent, regular administration of low, but pharmacologically active drug doses, optimizes antitumor efficacy by targeting multiple targets and reducing toxicity of antineoplastic drugs. This minireview will summarize preclinical and clinical studies on cytotoxic drugs given at weekly, daily, or at continuous metronomic schedules alone or in combination with novel targeted agents for hematological malignancies, including lymphoma, multiple myeloma, and leukemia. Most of the preclinical in vitro and in vivo studies have reported a significant benefit of both mCHEMO monotherapy and combinatorial regimens compared with chemotherapy at the maximum tolerated dose. However, the combination of mCHEMO with targeted drugs is still little explored in the hematologic clinical setting. Data obtained from preclinical studies on low dose metronomic chemotherapy in hematological malignancies clearly suggested the possibility to clinically investigate more tolerable and effective strategies for the treatment of patients with advanced hematological malignancies, or at least for those frail and elderly patients, who are not eligible or resistant to standard treatments.
Topics: Humans; Administration, Metronomic; Hematologic Neoplasms; Antineoplastic Agents; Animals; Antineoplastic Combined Chemotherapy Protocols
PubMed: 38636896
DOI: 10.1016/j.canlet.2024.216900 -
Investigational New Drugs Jun 2017In recent years, many anticancer drugs have been tested at metronomic dosages for a variety of tumours. Mechanisms of action attributed to metronomic chemotherapy (MCT)... (Review)
Review
In recent years, many anticancer drugs have been tested at metronomic dosages for a variety of tumours. Mechanisms of action attributed to metronomic chemotherapy (MCT) include antiangiogenesis, immunomodulation, direct inhibition of tumour growth, effect on tumour initiating cells and the modulation of clonal evolution. An active clinical research, aimed at testing MCT in several cancers, has been conducted over the past 15 years. However, because the majority of available results come from earlier phase II studies, mainly performed in the area of breast cancer (BC), it is clear that there are areas still to be investigated. We considered current studies dealing with MCT according to the clinical setting of patients. Despite a certain degree of overlap, we were able to identify four main clinical indications for MCT: refractory disease and frailty of patients, advanced stage disease (requiring first and second-line therapy), early stage disease and maintenance therapy after induction chemotherapy. In addition, a section of this review has been addressed to the combination of MCT with immunotherapy following the growing interest in the reinstatement of immune-surveillance. Crucial questions, such as the definition of optimal schedules of continuously delivered, low-dose chemotherapy and the recognition and validation of predictive biomarkers, need to be further addressed. Moreover, comparisons with the best supportive care are especially lacking and thus urgently awaited to establish the key role of MCT in the care of pretreated and frail patients. Maintenance therapy promises to be one of the most worthwhile developments for MCT. Currently, several combination strategies with standard chemotherapy, target agents or immunotherapy are under investigation but further efforts are needed to fill the gaps of knowledge in this field.
Topics: Administration, Metronomic; Animals; Antineoplastic Agents; Frailty; Humans; Immunotherapy; Neoplasms
PubMed: 27909934
DOI: 10.1007/s10637-016-0408-x -
Archives of Pharmacal Research Jan 2019Drug resistance and toxic side effects are major therapeutic hurdles affecting cancer patients receiving conventional chemotherapy based on the maximum tolerated dose.... (Review)
Review
Drug resistance and toxic side effects are major therapeutic hurdles affecting cancer patients receiving conventional chemotherapy based on the maximum tolerated dose. Metronomic chemotherapy (MCT), a new therapeutic approach developed to avoid these problems generally, consists of the continuous administration of low-dose cytotoxic agents without extended intervals. This therapy targets the tumor microenvironment, rather than exerting a direct effect on tumor cells. As a result, the MCT regimen functionally impairs tumor endothelial cells and circulating endothelial progenitor cells, leading to tumor dormancy via anti-angiogenesis. Over the past 10 years, several studies have highlighted the impact of MCT on the tumor microenvironment and angiogenesis and demonstrated its potential as a switch from the pro-angiogenic to the anti-angiogenic state. However, the mechanisms of action are still obscure. Here, we systematically review the evidence regarding the anti-angiogenic potential of MCT as a crucial determinant of tumor dormancy and cancer treatment.
Topics: Administration, Metronomic; Animals; Antineoplastic Agents; Endothelial Cells; Humans; Neoplasms; Neoplastic Cells, Circulating; Tumor Microenvironment
PubMed: 30604201
DOI: 10.1007/s12272-018-01102-z -
Cancer Letters Aug 2017Patients with esophagogastric cancer have poor prognoses in spite of the best available therapies. Patients are debilitated and may not tolerate, or may progress, on... (Review)
Review
Patients with esophagogastric cancer have poor prognoses in spite of the best available therapies. Patients are debilitated and may not tolerate, or may progress, on standard cytotoxic chemotherapy regimens. Metronomic chemotherapy is an attractive treatment option due to its very low reported toxicity, modest efficacy, low cost and ease of administration. Capecitabine is the most common drug used in metronomic scheduling; other drugs include cyclophosphamide and paclitaxel. Dosing of capecitabine can range from 1000 mg orally daily for 4 weeks on and 1 week off to a continuous dosing schedule of 1500 mg orally daily. Reported toxicities, including neutropenia, mucositis and hand-foot syndrome, occur in <10% of patients. As there is a lack of well-conducted, randomized clinical trials evaluating the role of metronomic chemotherapy in esophagogastric cancer, it cannot be recommended as the standard of care; however, it can be considered to be a therapeutic option, especially in elderly patients with relapsed disease for whom other therapeutic options are limited.
Topics: Administration, Metronomic; Antineoplastic Agents; Capecitabine; Cyclophosphamide; Esophageal Neoplasms; Evidence-Based Medicine; Humans; Paclitaxel; Patient Selection; Stomach Neoplasms; Treatment Outcome
PubMed: 28109908
DOI: 10.1016/j.canlet.2017.01.017 -
Aging Apr 2016
Topics: Administration, Metronomic; Animals; Antineoplastic Agents; Female; Humans; Triple Negative Breast Neoplasms
PubMed: 27084985
DOI: 10.18632/aging.100947 -
Critical Reviews in Oncology/hematology Jan 2021COVID 19 pandemic represents an emergency for public health services and containment measures to reduce the risk of infection have been promptly activated worldwide. The... (Review)
Review
COVID 19 pandemic represents an emergency for public health services and containment measures to reduce the risk of infection have been promptly activated worldwide. The healthcare systems reorganization has had a major impact on the management of cancer patients who are considered at high risk of infection. Recommendations and guidelines on how to manage cancer patients during COVID 19 pandemic have been published. Oral administration of chemotherapy is recommended to limit the access of cancer patients to hospital facilities and in some cases to guarantee the continuum of care. Low-dose metronomic administration of chemotherapy with different drugs and schedules has emerged in the last years as a possible alternative to conventional chemotherapy, due to its promising tumor control rates and excellent safety profiles. Moreover, given that many metronomic schedules use the oral route administration, it could represent a therapeutic strategy to ensure continuum of cancer care during COVID 19 pandemic. In this review we have selected all the clinical studies that have used the metronomic strategy, especially with oral drugs, in order to identify the subgroups of cancer patients who can benefit most from a metronomic approach even during COVID 19 pandemic.
Topics: Administration, Metronomic; Antineoplastic Combined Chemotherapy Protocols; COVID-19; Humans; Neoplasms; Pandemics; SARS-CoV-2
PubMed: 33254036
DOI: 10.1016/j.critrevonc.2020.103148 -
Cancer Letters Aug 2017We present a rationale for further clinical development and assessment of metronomic chemotherapy on the basis of unexpected results obtained in translational mouse... (Review)
Review
We present a rationale for further clinical development and assessment of metronomic chemotherapy on the basis of unexpected results obtained in translational mouse models of cancer involving treatment of advanced metastatic disease. Historically, mouse cancer therapy models have been dominated by treating established primary tumors or early stage low volume microscopic disease. Treatment of primary tumors is also almost always the case when using genetically engineered mouse models (GEMMs) of cancer or patient-derived xenografts (PDXs). Studies using such models, and others including transplanted cell lines, often yield highly encouraging results which are seldom recapitulated in the clinic, especially when assessed in randomized phase III clinical trials. While there are likely many different reasons for this discrepancy, one is likely the failure to recapitulate treatment of advanced visceral metastatic disease in mice. With this gap in mind, we have developed a number of models of metastatic human tumor xenografts (and more recently, of mouse tumors in syngeneic immunocompetent mice). A pattern of response we have observed with various targeted agents, e.g. VEGF pathway targeting antiangiogenic drugs or trastuzumab, is effective when treating primary tumors in contrast to a complete or severely reduced lack of such efficacy when treating advanced metastatic disease. Interestingly, an exception to this pattern has been observed using various continuous low-dose metronomic chemotherapy regimens, where counterintuitively, superior responses are observed in the metastatic setting, as well as superiority or equivalence of metronomic chemotherapy over standard maximum tolerated dose (MTD) chemotherapy, with lesser toxicity. The basis for these encouraging results may be related to the multiple mechanisms responsible for the anti-tumor effects and longer duration of metronomic chemotherapy regimens made possible by lesser toxicity. These include antiangiogenesis, stimulation of the immune system, stromal cell targeting in tumors, and possibly direct tumor cell targeting, including targeting cancer stem cells (CSCs). In addition, metronomic chemotherapy regimens minimize or even eliminate the problem of chemotherapy-induced host responses that may actually secondarily promote tumor growth and malignancy after causing an initial and beneficial anti-tumor response. We suggest that future preclinical studies of metronomic chemotherapy should be concentrated in the following areas: i) further comparative assessment of anti-tumor efficacy in primary vs metastatic treatment settings; ii) rigorous comparative assessment of conventional MTD chemotherapy vs metronomic chemotherapy using the same agent; iii) assessment of potential predictive biomarkers for metronomic chemotherapy, and methods to determine optimal biologic dose and schedule; and iv) a further detailed assessment of the potential of different chemotherapy drugs administered using MTD or metronomic regimens on stimulating or suppressing components of the innate or adaptive immune systems.
Topics: Administration, Metronomic; Angiogenesis Inhibitors; Animals; Antineoplastic Combined Chemotherapy Protocols; Cell Line, Tumor; Humans; Mice; Neoplasm Metastasis; Neoplasms, Experimental; Neovascularization, Pathologic; Time Factors; Tumor Burden; Xenograft Model Antitumor Assays
PubMed: 28202353
DOI: 10.1016/j.canlet.2017.02.005