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Pediatric Blood & Cancer Sep 2019Metronomic chemotherapy transitioned from the bench to bedside in the early 2000s and since then has carved a niche for itself in pediatric oncology. It has been used... (Review)
Review
Metronomic chemotherapy transitioned from the bench to bedside in the early 2000s and since then has carved a niche for itself in pediatric oncology. It has been used solely or in combination with other modalities such as radiotherapy, maximum tolerated dose chemotherapy, and targeted agents in adjuvant, palliative, as well as maintenance settings. No wonder, the resulting medical literature is extremely heterogeneous. In this review, the authors review and synthesize the published literature in pediatric metronomics giving a glimpse of its history, varied applications, and evolution of this genre of chemotherapy in pediatric cancers. Limitations, future prospects, and grey areas are also highlighted.
Topics: Administration, Metronomic; Child; Humans; Neoplasms
PubMed: 31207063
DOI: 10.1002/pbc.27811 -
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 -
Journal of Clinical Medicine May 2022Metastatic castration-resistant prostate cancer (mCRPC) is the ultimately lethal form of prostate cancer. Docetaxel chemotherapy was the first life-prolonging treatment... (Review)
Review
Metastatic castration-resistant prostate cancer (mCRPC) is the ultimately lethal form of prostate cancer. Docetaxel chemotherapy was the first life-prolonging treatment for mCRPC; however, the standard maximally tolerated dose (MTD) docetaxel regimen is often not considered for patients with mCRPC who are older and/or frail due to its toxicity. Low-dose metronomic chemotherapy (LDMC) is the frequent administration of typically oral and off-patent chemotherapeutics at low doses, which is associated with a superior safety profile and higher tolerability than MTD chemotherapy. We conducted a systematic literature review using the PUBMED, EMBASE, and MEDLINE electronic databases to identify clinical studies that examined the impact of LDMC on patients with advanced prostate cancer. The search identified 30 reports that retrospectively or prospectively investigated LDMC, 29 of which focused on mCRPC. Cyclophosphamide was the most commonly used agent integrated into 27/30 (90%) of LDMC regimens. LDMC resulted in a clinical benefit rate of 56.8 ± 24.5% across all studies. Overall, there were only a few non-hematological grade 3 or 4 adverse events reported. As such, LDMC is a well-tolerated treatment option for patients with mCRPC, including those who are older and frail. Furthermore, LDMC is considered more affordable than conventional mCRPC therapies. However, prospective phase III trials are needed to further characterize the efficacy and safety of LDMC in mCRPC before its use in practice.
PubMed: 35628909
DOI: 10.3390/jcm11102783 -
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 -
Cancer Letters Oct 2023Low-dose metronomic (LDM) chemotherapy, the frequent and continuous use of low doses of conventional chemotherapeutics, is emerging as a promising form of chemotherapy...
Low-dose metronomic (LDM) chemotherapy, the frequent and continuous use of low doses of conventional chemotherapeutics, is emerging as a promising form of chemotherapy utilization. LDM chemotherapy exerts immunomodulatory effects. However, the underlying mechanism is not fully understood. Here we found that suppressing tumor growth by LDM chemotherapy was dependent on the activation of CD8T cells. LDM chemotherapy potentiated the cytotoxic function of CD8T cells by stimulating cancer-cell autonomous type I interferon (IFN) induction. Mechanistically, LDM chemotherapy evoked mitochondrial dysfunction and increased reactive oxygen species (ROS) production. ROS triggered the oxidation of cytosolic mtDNA, which was sensed by cGAS-STING, consequently inducing type I IFN production in the cancer cells. Moreover, the cGAS-STING-IFN axis increased PD-L1 expression and predicted favorable clinical responses to chemoimmunotherapy. Antioxidant N-acetylcysteine inhibited oxidized mtDNA-induced type I IFN production and attenuated the efficacy of combination therapy with LDM chemotherapy and PD-L1 blockade. This study elucidates the critical role of intratumoral oxidized mtDNA sensing in LDM chemotherapy-mediated activation of CD8T cell immune response. These findings may provide new insights for designing combinatorial immunotherapy for cancer patients.
Topics: Humans; DNA, Mitochondrial; B7-H1 Antigen; Reactive Oxygen Species; Mitochondria; CD8-Positive T-Lymphocytes
PubMed: 37660883
DOI: 10.1016/j.canlet.2023.216370 -
Cancer Treatment Reviews Sep 2020Metronomic chemotherapy (M-CT) is defined as dose dense administration of chemotherapy at lower doses than maximum tolerated dose but at shorter free intervals, to... (Review)
Review
Metronomic chemotherapy (M-CT) is defined as dose dense administration of chemotherapy at lower doses than maximum tolerated dose but at shorter free intervals, to obtain a near continuous exposure of cancer cells to those potentially effective drugs. M-CT is a useful strategy to obtain response, overcome resistance and reduce side effects, with low costs. This review will focus on the use of M-CT in advanced breast cancer (ABC). Cytostatic and cytotoxic effect on cancer cells, the anti-angiogenic and the immunomodulatory effects are its main mechanisms of actions. Many clinical trials proved the efficacy and tolerability of different monotherapies and combinations of chemotherapeutic agents administered in metronomic doses and frequencies in ABC. M-CT is a reasonable option for second and later lines of chemotherapy in metastatic breast cancer including those with prior anthracycline or taxane exposure, older patients and patients with comorbidities, and even as first-line in certain groups of patients. The acceptable efficacy and low toxicity of oral metronomic chemotherapy makes it a reasonable option during COVID-19 pandemic as well as in the post-COVID era which is projected to last for some time.
Topics: Administration, Metronomic; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; COVID-19; Clinical Trials, Phase II as Topic; Coronavirus Infections; Female; Humans; Neoplasm Metastasis; Pandemics; Pneumonia, Viral; Randomized Controlled Trials as Topic
PubMed: 32769038
DOI: 10.1016/j.ctrv.2020.102066 -
International Journal of Molecular... Oct 2019Low dose metronomic chemotherapy (MC) is becoming a mainstream treatment for cancer in veterinary medicine. Its mechanism of action is anti-angiogenesis by lowering... (Review)
Review
Low dose metronomic chemotherapy (MC) is becoming a mainstream treatment for cancer in veterinary medicine. Its mechanism of action is anti-angiogenesis by lowering vascular endothelial growth factor (VEGF) and increasing trombospondin-1 (TSP1). It has also been adopted as a compassionate treatment in very advanced human cancer. However, one of the main limitations of this therapy is its short-term effectiveness: 6 to 12 months, after which resistance develops. pH-centered cancer treatment (pHT) has been proposed as a complementary therapy in cancer, but it has not been adopted or tested as a mainstream protocol, in spite of existing evidence of its advantages and benefits. Many of the factors directly or indirectly involved in MC and anti-angiogenic treatment resistance are appropriately antagonized by pHT. This led to the testing of an association between these two treatments. Preliminary evidence indicates that the association of MC and pHT has the ability to reduce anti-angiogenic treatment limitations and develop synergistic anti-cancer effects. This review will describe each of these treatments and will analyze the fundamentals of their synergy.
Topics: Administration, Metronomic; Angiogenesis Inhibitors; Antineoplastic Combined Chemotherapy Protocols; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; Drug Synergism; Humans; Hydrogen-Ion Concentration; Neoplasms; Neovascularization, Pathologic; Vascular Endothelial Growth Factor A
PubMed: 31683667
DOI: 10.3390/ijms20215438 -
Cancer Letters Nov 2023This scientometric study aimed to provide a first comprehensive overview of the global research landscape of Metronomic Chemotherapy (MC) from 2000 to 2022 using a...
This scientometric study aimed to provide a first comprehensive overview of the global research landscape of Metronomic Chemotherapy (MC) from 2000 to 2022 using a data-driven approach to identify key trends, collaborations, and potential opportunities. This study highlights the increasing prevalence of MC, with annual outputs increasing substantially over the same timeframe. The United States contributed the most to MC research, followed by Italy and China, while there was a lack of collaborative research efforts between countries and organizations. Through keyword co-occurrence analysis, we identified emerging interdisciplinary research areas, such as "nanoparticles," "immunotherapy," and "antitumor immunity." Our citation analysis identified the most influential authors, institutions, and journals, providing a comprehensive overview of the structure of knowledge and dissemination of MC research. Although the number of publications has decreased since 2019, the analysis indicates that this field has received substantial scholarly attention. These discoveries are extremely important for researchers, funding organizations, and policymakers because they highlight the need for more collaboration, interdisciplinary approaches, and resource allocation in underrepresented fields. This study concludes with recommendations for guiding future research and collaboration, resulting in a larger impact and fostering substantial advancements in MC research.
PubMed: 37774827
DOI: 10.1016/j.canlet.2023.216401 -
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 -
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