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metronomic chemotherapy

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https://www.readbyqxmd.com/read/28216371/atp-binding-cassette-transporters-in-tumor-endothelial-cells-and-resistance-to-metronomic-chemotherapy
#1
Kyoko Hida, Hiroshi Kikuchi, Nako Maishi, Yasuhiro Hida
Drug resistance is a major problem in anticancer therapy. ATP-binding cassette (ABC) transporters have a role in the multidrug resistance. A new regimen of chemotherapy has been proposed, called "metronomic chemotherapy". Metronomic chemotherapy is the frequent, regular administration of drug doses designed to maintain low, but active, concentrations of chemotherapeutic drugs over prolonged periods of time, without causing serious toxicities. Metronomic chemotherapy regimens were developed to optimize the antitumour efficacy of agents that target the tumour vasculature instead of tumour cells, and to reduce toxicity of antineoplastic drugs" [1]...
February 16, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28202353/the-potential-clinical-promise-of-multimodality-metronomic-chemotherapy-revealed-by-preclinical-studies-of-metastatic-disease
#2
Robert S Kerbel, Yuval Shaked
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)...
February 12, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28174262/role-of-vascular-normalization-in-benefit-from-metronomic-chemotherapy
#3
Fotios Mpekris, James W Baish, Triantafyllos Stylianopoulos, Rakesh K Jain
Metronomic dosing of chemotherapy-defined as frequent administration at lower doses-has been shown to be more efficacious than maximum tolerated dose treatment in preclinical studies, and is currently being tested in the clinic. Although multiple mechanisms of benefit from metronomic chemotherapy have been proposed, how these mechanisms are related to one another and which one is dominant for a given tumor-drug combination is not known. To this end, we have developed a mathematical model that incorporates various proposed mechanisms, and report here that improved function of tumor vessels is a key determinant of benefit from metronomic chemotherapy...
February 7, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28133740/toxicity-of-metronomic-cyclophosphamide-chemotherapy-in-a-uk-population-of-cancer-bearing-dogs-a-retrospective-study
#4
A Harper, L Blackwood
OBJECTIVES: The objective of this study was to assess the incidence of toxicity in a group of cancer-bearing dogs treated with metronomic chemotherapy. MATERIALS AND METHODS: Retrospective review of dogs treated with metronomic doses of cyclophosphamide: between 5 and 15 mg/m(2) /day or every other day for treatment of neoplasia. RESULTS: Of the 65 dogs included, there were signs of, mostly mild, toxicity in 32 (49%). The most common toxicities were sterile haemorrhagic cystitis (n=16) and gastrointestinal disorders (n=12)...
January 30, 2017: Journal of Small Animal Practice
https://www.readbyqxmd.com/read/28131905/safety-and-efficacy-study-of-metronomic-vinorelbine-cyclophosphamide-plus-capecitabine-in-metastatic-breast-cancer-a-phase-ii-trial
#5
Emilia Montagna, Antonella Palazzo, Patrick Maisonneuve, Giuseppe Cancello, Monica Iorfida, Angela Sciandivasci, Angela Esposito, Anna Cardillo, Manuelita Mazza, Elisabetta Munzone, Antonella Lai, Aron Goldhirsch, Marco Colleoni
In a phase II study we assessed the safety and efficacy of metronomic oral chemotherapy with vinorelbine, cyclophosphamide capecitabine in patients with metastatic breast cancer, either as first-line (naïve group) or second-line or greater therapy (pre-treated group). Eligible patients had histologically or cytologically proven, hormone-receptor positive metastatic breast cancer. The primary end point was median time to progression (TTP). A total of 43 patients in the naïve group and 65 in the pre-treated group were enrolled...
January 26, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28109908/potential-role-of-metronomic-chemotherapy-in-the-treatment-of-esophageal-and-gastroesophageal-cancer
#6
Vanita Noronha, Vijay M Patil, Amit Joshi, Anuradha Chougule, Shripad Banavali, Kumar Prabhash
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...
January 18, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28093298/metronomic-chemotherapy-using-orally-active-carboplatin-deoxycholate-complex-to-maintain-drug-concentration-within-a-tolerable-range-for-effective-cancer-management
#7
Foyez Mahmud, Seung Woo Chung, Farzana Alam, Jeong Uk Choi, Seong Who Kim, In-San Kim, Sang Yoon Kim, Dong Soo Lee, Youngro Byun
Metronomic chemotherapy has translated into favorable toxicity profile and capable of delaying tumor progression. Despite its promise, conventional injectable chemotherapeutics are not meaningful to use as metronomic due to the necessity of frequent administration for personalized therapy in long-term cancer treatments. This study aims to exploit the benefits of the oral application of carboplatin as metronomic therapy for non-small cell lung cancer (NSCLC). We developed an orally active carboplatin by physical complexation with a deoxycholic acid (DOCA)...
January 16, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28093280/metronomics-in-the-neoadjuvant-and-adjuvant-treatment-of-breast-cancer
#8
Elisabetta Munzone, Marco Colleoni
The concept of metronomic chemotherapy (MC) has evolved from a descriptive preclinical phenomenon encompassing inhibition of angiogenesis to a clinically validated treatment concept involving multiple potential mechanisms of action. Clinicians are progressively more incline to consider MC as a component of mainstream medical oncology practice in advanced breast cancer. However, more recently MC has been tested even in the adjuvant/neoadjuvant setting, taking the opportunity to obtain tumor specimens and blood samples, in order to identify tumor-specific or patient-specific biomarkers for personalizing treatments...
January 16, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28088627/the-telomere-binding-protein-trf2-is-required-for-metronomic-therapeutic-effects-of-gemcitabine-and-capecitabine
#9
Wei-Ping Lee, Keng-Hsin Lan, Chung-Pin Li, Yee Chao, Ming-Chih Hou, Han-Chieh Lin, Shou-Dong Lee
Gemcitabine and capecitabine are two effective anticancer agents against solid tumors. The pharmacological mechanisms have been known as incorporation into DNA and thereby inhibition of DNA synthesis. When used as metronomic chemotherapy, they may inhibit angiogenesis and induce immunity. In our previous study, we showed that low-dose gemcitabine caused telomere shortening by stabilizing TRF2 that was required for XPF-dependent telomere loss. In this report, we established a SKOV3.ip1 ascites cell model. Tumor-bearing mice were treated with low-dose gemcitabine (GEM) or capecitabine (CAP)...
January 11, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28056464/impact-of-ctla-4-blockade-in-conjunction-with-metronomic-chemotherapy-on-preclinical-breast-cancer-growth
#10
Karla Parra, Paloma Valenzuela, Natzidielly Lerma, Alejandra Gallegos, Luis C Reza, Georgialina Rodriguez, Urban Emmenegger, Teresa Di Desidero, Guido Bocci, Mitchell S Felder, Marian Manciu, Robert A Kirken, Giulio Francia
BACKGROUND: Although there are reports that metronomic cyclophosphamide (CTX) can be immune stimulating, the impact of its combination with anti-CTLA-4 immunotherapy for the treatment of cancer remains to be evaluated. METHODS: Murine EMT-6/P breast cancer, or its cisplatin or CTX-resistant variants, or CT-26 colon, were implanted into Balb/c mice. Established tumours were monitored for relative growth following treatment with anti-CTLA-4 antibody alone or in combination with; (a) metronomic CTX (ldCTX; 20 mg kg(-1) day(-1)), b) bolus (150 mg kg(-1)) plus ldCTX, or (c) sequential treatment with gemcitabine (160 mg kg(-1) every 3 days)...
January 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28050393/metronomic-chemotherapy-seems-prowess-to-battle-against-cancer-in-current-scenario
#11
Prema Muthusamy, Krishnan Vengadaragava Chary, G K Nalini
INTRODUCTION: Metronomic chemotherapy is an emerging method of chemotherapy. Metronomic 'lowdose' chemotherapy regimen induces tumour dormancy and reduces cancer resistance against anticancer drugs. It tends to improve overall success rate of cancer chemotherapy than conventional cyclical regimen. AIM: The aim of this systemic review was to provide comprehensive data of metronomic chemotherapy trials, regimens used and it's outcome in cancer therapeutics. MATERIALS AND METHODS: Fifty chemotherapy trial data were searched sequentially from web...
November 2016: Journal of Clinical and Diagnostic Research: JCDR
https://www.readbyqxmd.com/read/28042155/evaluation-of-toxicity-of-a-chronic-alternate-day-metronomic-cyclophosphamide-chemotherapy-protocol-in-dogs-with-naturally-occurring-cancer
#12
Arata Matsuyama, J Paul Woods, Anthony J Mutsaers
Sterile hemorrhagic cystitis (SHC) is an important complication of cyclophosphamide chemotherapy in dogs as it is reported in up to 23% of cases with various protocols. The current study reports toxicities of a protocol of metronomic cyclophosphamide, and identifies risk factors for development of adverse effects. A retrospective cohort study of dogs treated with metronomic cyclophosphamide at an intended dose of 25 mg/m(2) every other day was conducted. Fifty dogs were included with a median length of treatment of 90 days (range: 1 to 1305 days)...
January 2017: Canadian Veterinary Journal. la Revue Vétérinaire Canadienne
https://www.readbyqxmd.com/read/28039473/nanometronomic-treatment-of-4t1-breast-cancer-with-nanocaged-doxorubicin-prevents-drug-resistance-and-circumvents-cardiotoxicity
#13
Serena Mazzucchelli, Michela Bellini, Luisa Fiandra, Marta Truffi, Maria A Rizzuto, Luca Sorrentino, Erika Longhi, Manuela Nebuloni, Davide Prosperi, Fabio Corsi
Chemotherapeutic treatment of breast cancer is based on maximum tolerated dose (MTD) approach. However, advanced stage tumors are not effectively eradicated by MTD owing to suboptimal drug targeting, onset of therapeutic resistance and neoangiogenesis. In contrast, "metronomic" chemotherapy is based on frequent drug administrations at lower doses, resulting in neovascularization inhibition and induction of tumor dormancy. Here we show the potential of H-ferritin (HFn)-mediated targeted nanodelivery of metronomic doxorubicin (DOX) in the setting of a highly aggressive and metastatic 4T1 breast cancer mouse model with DOX-inducible expression of chemoresistance...
January 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/28017894/metronomic-chemotherapy-for-advanced-breast-cancer-patients
#14
Marina Elena Cazzaniga, Maria Rita Dionisio, Francesca Riva
Metronomic chemotherapy refers to the minimum biologically effective dose of a chemotherapy agent given as a continuous dosing regimen with no prolonged drug-free breaks that leads to antitumor activity. This schedule seems to have not only a direct cytotoxicity on cancer cells but also an effect on the tumor microenvironment by inhibiting tumor angiogenesis and modulating immune response. Metronomic chemotherapy was widely investigated in patients with breast cancer. The results of these studies showed that this strategy is not only effective but has a low toxicity profile too, proposing as a promising strategy for breast cancer patients...
December 23, 2016: Cancer Letters
https://www.readbyqxmd.com/read/28017892/metronomic-chemotherapy-a-potent-macerator-of-cancer-by-inducing-angiogenesis-suppression-and-antitumor-immune-activation
#15
Eirini Biziota, Leonidas Mavroeidis, Eleftheria Hatzimichael, Periklis Pappas
Metronomic chemotherapy is a low dosing treatment strategy that attracts growing scientific and clinical interest. It refers to dense and uninterrupted administration of low doses of chemotherapeutic agents (without prolonged drug free intervals) over extended periods of time. Cancer chemotherapy is conventionally given in cycles of maximum tolerated doses (MTD) with the aim of inducing maximum cancer cell apoptosis. In contrast, the primary target of metronomic chemotherapy is the tumor's neovasculature. This is relevant to the emerging concept that tumors exist in a complex microenvironment of cancer cells, stromal cells and supporting vessels...
December 23, 2016: Cancer Letters
https://www.readbyqxmd.com/read/28003122/metronomic-chemotherapy-a-relook-at-its-basis-and-rationale
#16
Tanujaa Rajasekaran, Quan-Sing Ng, Daniel Shao-Weng Tan, Wan-Teck Lim, Mei-Kim Ang, Chee-Keong Toh, Balram Chowbay, Ravindran Kanesvaran, Eng-Huat Tan
Metronomic administration of chemotherapy has long been recognized as having a different biological effect from maximal tolerated dose (MTD) administration. Preclinical studies have demonstrated these differences quite elegantly and many clinical trials have also demonstrated reproducible activity albeit small, in varied solid malignancies even in patients who were heavily pretreated. However, the concept of metronomic chemotherapy has been plagued by lack of a clear definition resulting in the published literature that is rather varied and confusing...
March 1, 2017: Cancer Letters
https://www.readbyqxmd.com/read/27994645/next-generation-metronomic-chemotherapy-report-from-the-fifth-biennial-international-metronomic-and-anti-angiogenic-therapy-meeting-6-8-may-2016-mumbai
#17
Pan Pantziarka, Lisa Hutchinson, Nicolas André, Sébastien Benzekry, Francesco Bertolini, Atanu Bhattacharjee, Shubhada Chiplunkar, Dan G Duda, Vikram Gota, Sudeep Gupta, Amit Joshi, Sadhana Kannan, Robert Kerbel, Mark Kieran, Antonella Palazzo, Aparna Parikh, Eddy Pasquier, Vijay Patil, Kumar Prabhash, Yuval Shaked, Giselle Saulnier Sholler, Jaroslav Sterba, David J Waxman, Shripad Banavali
The 5(th) Biennial Metronomic and Anti-angiogenic Therapy Meeting was held on 6(th) - 8(th) May in the Indian city of Mumbai. The meeting brought together a wide range of clinicians and researchers interested in metronomic chemotherapy, anti-angiogenics, drug repurposing and combinations thereof. Clinical experiences, including many from India, were reported and discussed in three symposia covering breast cancer, head and neck cancers and paediatrics. On the pre-clinical side research into putative mechanisms of action, and the interactions between low dose metronomic chemotherapy and angiogenesis and immune responses, were discussed in a number of presentations...
2016: Ecancermedicalscience
https://www.readbyqxmd.com/read/27909934/current-achievements-and-future-perspectives-of-metronomic-chemotherapy
#18
REVIEW
Adriana Romiti, Rosa Falcone, Michela Roberto, Paolo Marchetti
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...
December 1, 2016: Investigational New Drugs
https://www.readbyqxmd.com/read/27901449/incidence-of-sterile-hemorrhagic-cystitis-in-tumor-bearing-dogs-concurrently-treated-with-oral-metronomic-cyclophosphamide-chemotherapy-and-furosemide-55-cases-2009-2015
#19
Catherine M Chan, Angela E Frimberger, Antony S Moore
OBJECTIVE To determine the incidence of sterile hemorrhagic cystitis (SHC) in tumor-bearing dogs concurrently treated with oral metronomic cyclophosphamide chemotherapy and furosemide. DESIGN Retrospective case series. ANIMALS 55 dogs. PROCEDURES Record databases of 2 specialty practices were searched to identify dogs treated with oral metronomic cyclophosphamide chemotherapy in conjunction with furosemide for a minimum of 28 days between January 2009 and December 2015. Information extracted from the records included signalment, tumor diagnosis, cyclophosphamide and furosemide dosages, and concurrent medications...
December 15, 2016: Journal of the American Veterinary Medical Association
https://www.readbyqxmd.com/read/27881735/therapy-activated-stromal-cells-can-dictate-tumor-fate
#20
Robert S Kerbel, Yuval Shaked
In this issue of JEM, Chan et al. describe a novel way by which an investigational form of chemotherapy known as low-dose metronomic chemotherapy can inhibit tumor growth, which also has therapeutic implications for targeting tumor-initiating cells (TICs), the tumor stroma, and chemokine receptors, as well as invasion and metastasis.
December 12, 2016: Journal of Experimental Medicine
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