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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 -
Cancer Letters Jul 2024Current methods of cancer therapy have demonstrated enormous potential in tumor inhibition. However, a high dosage regimen of chemotherapy results in various... (Review)
Review
Current methods of cancer therapy have demonstrated enormous potential in tumor inhibition. However, a high dosage regimen of chemotherapy results in various complications which affect the normal body cells. Tumor cells also develop resistance against the prescribed drugs in the whole treatment regimen increasing the risk of cancer relapse. Metronomic chemotherapy is a modern treatment method that involves administering drugs at low doses continuously, allowing the drug sufficient time to take its effect. This method ensures that the toxicity of the drugs is to a minimum in comparison to conventional chemotherapy. Nanoparticles have shown efficacy in delivering drugs to the tumor cells in various cancer therapies. Combining nanoparticles with metronomic chemotherapy can yield better treatment results. This combination stimulates the immune system, improving cancer cells recognition by immune cells. Evidence from clinical and pre-clinical trials supports the use of metronomic delivery for drug-loaded nanoparticles. This review focuses on the functionalization of nanoparticles for improved drug delivery and inhibition of tumor growth. It emphasizes the mechanisms of metronomic chemotherapy and its conjunction with nanotechnology. Additionally, it explores tumor progression and the current methods of chemotherapy. The challenges associated with nano-based metronomic chemotherapy are outlined, paving the way for prospects in this dynamic field.
Topics: Humans; Administration, Metronomic; Neoplasms; Nanoparticles; Antineoplastic Agents; Animals; Drug Delivery Systems; Drug Carriers
PubMed: 38801886
DOI: 10.1016/j.canlet.2024.216990 -
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