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Cancers Oct 2022Medulloblastoma (MB) recurrence is usually incurable despite intensive therapy including high-dose chemotherapy. An evolving alternative approach to conventional...
Medulloblastoma (MB) recurrence is usually incurable despite intensive therapy including high-dose chemotherapy. An evolving alternative approach to conventional chemotherapy aims at interfering with tumor angiogenesis at different levels. We report on a novel combinatorial metronomic antiangiogenic approach. The study is a retrospective observational study of 29 consecutive patients with first or multiple recurrences prospectively treated according to the MEMMAT strategy ("MEMMAT-like") before the formal protocol (MEMMAT; ClinicalTrials.gov Identifier: NCT01356290) started. The study period was 11/2006 to 06/2016. Treatment consisted of daily oral thalidomide, fenofibrate, celecoxib, and alternating 21-day cycles of low-dose oral etoposide and cyclophosphamide supplemented by IV bevacizumab and intraventricular therapy consisting of alternating etoposide and liposomal cytarabine. Median overall survival (OS) after recurrence for the whole group was 29.5 months, OS was 48.3 ± 9.3% at three years and 34.5 ± 8.8% at five years, and progression-free survival was 42.0 ± 9.5% at three years and 29.4 ± 9% at five years. As of 07/2022, 9/29 patients are alive 86 to 164 months after the recurrence that prompted the "MEMMAT-like" therapy. Treatment was primarily out-patient and generally well-tolerated. Toxicities did occur but were manageable. In conclusion, antiangiogenic therapy according to the MEMMAT strategy increased median OS of patients with recurrent MB and may lead to long-term survival. Adherence to the protocol, including intraventricular therapy, appears important.
PubMed: 36291912
DOI: 10.3390/cancers14205128 -
Current Oncology Reports Apr 2024This review describes the most relevant studies found in the scientific literature regarding metronomic chemotherapy (MCT) in the geriatric oncology population to... (Review)
Review
PURPOSE OF REVIEW
This review describes the most relevant studies found in the scientific literature regarding metronomic chemotherapy (MCT) in the geriatric oncology population to support its use as a feasible treatment of care in the frail elderly patients.
RECENT FINDINGS
Recent years have seen a reevaluation of cancer chemotherapeutic drugs and MCT is an emerging schedule in phase II and III clinical trials. Ageing is one of the risk factors for the development of cancer, the incidence of whom increases dramatically in people who live longer. To date, standard oncological protocols involve chemotherapeutic drugs in short cycles of therapy at the maximum tolerated dose (MTD). Although these therapeutic regimens may be successful, they can cause important adverse drug reactions, especially in elderly or frail patients. MCT is a different modality of delivery of chemotherapeutic drugs (frequent low dose for prolonged time) and it looks at the overcoming of the limitations and disadvantages of MTD, in particular the toxicity aspect. We reviewed the experience of clinicians who have used MCT in clinical trials enrolling elderly patients with different cancer types.
Topics: Humans; Aged; Antineoplastic Agents; Neoplasms; Antineoplastic Combined Chemotherapy Protocols
PubMed: 38448722
DOI: 10.1007/s11912-024-01505-w -
Cureus Dec 2023Treatment of locally advanced oral cancer requires multidisciplinary care, including surgery, radiotherapy, and chemotherapy, which varies based on the stage of the... (Review)
Review
Treatment of locally advanced oral cancer requires multidisciplinary care, including surgery, radiotherapy, and chemotherapy, which varies based on the stage of the disease, site of involvement, and surgical access. Oral cancer usually presents with an increased recurrence rate and potential for distant metastatic spread. It confers a poor prognosis with a 50% mortality rate after five years. Oral metronomic chemotherapy aims to achieve higher patient compliance due to its ease of administration, lower dosage, and lesser side effects than conventional IV regimens of platinum-based drugs. In this review, we have summarized the relevant literature to benefit the readers regarding the potential application of metronomic therapy in the management of oral cancer.
PubMed: 38169679
DOI: 10.7759/cureus.49825 -
Cancers Apr 2023Increasing evidence pinpoints metronomic chemotherapy, a frequent and low dose drug administration with no prolonged drug-free intervals, as a potential tool to fight... (Review)
Review
Increasing evidence pinpoints metronomic chemotherapy, a frequent and low dose drug administration with no prolonged drug-free intervals, as a potential tool to fight certain types of cancers. The primary identified targets of metronomic chemotherapy were the tumor endothelial cells involved in angiogenesis. After this, metronomic chemotherapy has been shown to efficiently target the heterogeneous population of tumor cells and, more importantly, elicit the innate and adaptive immune system reverting the "cold" to "hot" tumor immunologic phenotype. Although metronomic chemotherapy is primarily used in the context of a palliative setting, with the development of new immunotherapeutic drugs, a synergistic therapeutic role of the combined metronomic chemotherapy and immune checkpoint inhibitors has emerged at both the preclinical and clinical levels. However, some aspects, such as the dose and the most effective scheduling, still remain unknown and need further investigation. Here, we summarize what is currently known of the underlying anti-tumor effects of the metronomic chemotherapy, the importance of the optimal therapeutic dose and time-exposure, and the potential therapeutic effect of the combined administration of metronomic chemotherapy with checkpoint inhibitors in preclinical and clinical settings.
PubMed: 37173937
DOI: 10.3390/cancers15092471 -
Journal of Clinical Medicine Jun 2021Metronomic therapy is characterized by drug administration in a low-dose, repeated, and regular manner without prolonged drug-free interval. The two main anticancer... (Review)
Review
Metronomic therapy is characterized by drug administration in a low-dose, repeated, and regular manner without prolonged drug-free interval. The two main anticancer mechanisms of metronomic therapy are antiangiogenesis and immunomodulation, which have been demonstrated in several delicate in vitro and in vivo experiments. In contrast to the traditional maximum tolerated dose (MTD) dosing of chemotherapy, metronomic therapy possesses comparative efficacy but greatlydecreases the incidence and severity of treatment side-effects. Clinical trials of metronomic anticancer treatment have revealed promising results in a variety cancer types and specific patient populations such as the elderly and pediatric malignancies. Oral cavity squamous cell carcinoma (OCSCC) is an important health issue in many areas around the world. Long-term survival is about 50% in locally advanced disease despite having high-intensity treatment combined surgery, radiotherapy, and chemotherapy. In this article, we review and summarize the essence of metronomic therapy and focus on its applications in OCSCC treatment.
PubMed: 34206730
DOI: 10.3390/jcm10132818 -
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 -
Frontiers in Oncology 2022The combinatory use of drugs for systemic cancer therapy commonly aims at the direct elimination of tumor cells through induction of apoptosis. An alternative approach... (Review)
Review
The combinatory use of drugs for systemic cancer therapy commonly aims at the direct elimination of tumor cells through induction of apoptosis. An alternative approach becomes the focus of attention if biological changes in tumor tissues following combinatory administration of regulatorily active drugs are considered as a therapeutic aim, e.g., differentiation, transdifferentiation induction, reconstitution of immunosurveillance, the use of alternative cell death mechanisms. Editing of the tumor tissue establishes new biological 'hallmarks' as a 'pressure point' to attenuate tumor growth. This may be achieved with repurposed, regulatorily active drug combinations, often simultaneously targeting different cell compartments of the tumor tissue. Moreover, tissue editing is paralleled by decisive functional changes in tumor tissues providing novel patterns of target sites for approved drugs. Thus, agents with poor activity in non-edited tissue may reveal new clinically meaningful outcomes. For tissue editing and targeting edited tissue novel requirements concerning drug selection and administration can be summarized according to available clinical and pre-clinical data. Monoactivity is no pre-requisite, but combinatory bio-regulatory activity. The regulatorily active dose may be far below the maximum tolerable dose, and besides inhibitory active drugs stimulatory drug activities may be integrated. Metronomic scheduling often seems to be of advantage. Novel preclinical approaches like functional assays testing drug combinations in tumor tissue are needed to select potential drugs for repurposing. The two-step drug repurposing procedure, namely establishing novel functional systems states in tumor tissues and consecutively providing novel target sites for approved drugs, facilitates the systematic identification of drug activities outside the scope of any original clinical drug approvals.
PubMed: 35814409
DOI: 10.3389/fonc.2022.900985 -
Pharmaceutics Apr 2023Cancer-related death is a significant health and economic burden worldwide, and some conventional chemotherapy is associated with limited effectiveness in completely... (Review)
Review
Cancer-related death is a significant health and economic burden worldwide, and some conventional chemotherapy is associated with limited effectiveness in completely curing various cancers, severe adverse effects, and destruction of healthy cells. To overcome the complications associated with conventional treatment, metronomic chemotherapy (MCT) is extensively suggested. In this review, we aim to highlight the importance of MCT over conventional chemotherapeutic approach with emphasis on nanoformulations-based MCT, their mechanism, challenges, recent advances, and future perspectives. Nanoformulations-based MCT revealed remarkable antitumor activity in both preclinical and clinical settings. For example, the metronomic scheduling of oxaliplatin-loaded nanoemulsion and polyethylene glycol-coated stealth nanoparticles incorporating paclitaxel were proven very effective in tumor-bearing mice and rats, respectively. Additionally, several clinical studies have demonstrated the benefit of MCT with acceptable tolerance. Moreover, metronomic might be a promising treatment strategy for improving cancer care in low- and middle-income nations. However, an appropriate alternative to a metronomic regimen for an individual ailment, suitable combinational delivery and scheduling, and predictive biomarkers are certain parts that remain unanswered. Further clinical-based comparative research studies are mandatory to be performed before entailing this treatment modality in clinical practice as alternative maintenance therapy or in place of transferring to therapeutic management.
PubMed: 37111677
DOI: 10.3390/pharmaceutics15041192 -
Journal of Clinical Medicine Aug 2022Metronomic chemotherapy (mCHT), defined as continuous administration of low-dose chemotherapeutic agents with no or short regular treatment-free intervals, was first... (Review)
Review
Metronomic chemotherapy (mCHT), defined as continuous administration of low-dose chemotherapeutic agents with no or short regular treatment-free intervals, was first introduced to the clinic in international guidelines in 2017, and, since then, has become one of the available strategies for the treatment of advanced breast cancer (ABC). Despite recent successes, many unsolved practical and theoretical issues remain to be addressed. The present review aims to identify the "lights and shadows" of mCHT in preclinical and clinical settings. In the preclinical setting, several findings indicate that one of the most noticeable effects of mCHT is on the tumor microenvironment, which, over the last twenty years, has been demonstrated to be pivotal in supporting tumor cell survival and proliferation. On the other hand, the direct effects on tumor cells have been less well-defined. In addition, critical items to be addressed are the lack of definition of an optimal biological dose (OBD), the method of administration of metronomic schedules, and the recognition and validation of predictive biomarkers. In the clinical context-where mCHT has mainly been used in a metastatic setting-low toxicity is the most well-recognised light of mCHT, whereas the type of study design, the absence of randomised trials and uncertainty in terms of doses and drugs remain among the shadows. In conclusion, growing evidence indicates that mCHT is a suitable treatment option for selected metastatic breast cancer (MBC) patients. Moreover, given its multimodal mechanisms of action, its addition to immunological and targeted therapies might represent a promising new approach to the treatment of MBC. More preclinical data are needed in this regard, which can only be obtained through support for translational research as the key link between basic science and patient care.
PubMed: 36012949
DOI: 10.3390/jcm11164710 -
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