Did you mean: 'metronomic chemotherapy'
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Journal of Oncology 2019Metronomic chemotherapy, continuous and dose-dense administration of chemotherapeutic drugs with lowered doses, is being evaluated for substituting, augmenting, or... (Review)
Review
Metronomic chemotherapy, continuous and dose-dense administration of chemotherapeutic drugs with lowered doses, is being evaluated for substituting, augmenting, or appending conventional maximum tolerated dose regimens, with preclinical and clinical studies for the past few decades. To date, the principle mechanisms of its action include impeding tumoral angiogenesis and modulation of hosts' immune system, affecting directly tumor cells, their progenitors, and neighboring stromal cells. Its better toxicity profile, lower cost, and easier use are main advantages over conventional therapies. The evidence of metronomic chemotherapy for personalized medicine is growing, starting with unfit elderly patients and also for palliative treatment. The literature reviewed in this article mainly demonstrates that metronomic chemotherapy is advantageous for selected patients and for certain types of malignancies, which make it a promising therapeutic approach for filling in the gaps. More clinical studies are needed to establish a solidified role for metronomic chemotherapy with other treatment models in modern cancer management.
PubMed: 31015835
DOI: 10.1155/2019/5483791 -
Medicine Nov 2022The current studies on metronomic chemotherapy in mCRC are all aimed at patients after multi-line therapy failure, and only a few studies have focused on maintenance...
BACKGROUND
The current studies on metronomic chemotherapy in mCRC are all aimed at patients after multi-line therapy failure, and only a few studies have focused on maintenance treatment after successful first-line therapy.
METHODS
The PubMed, Embase, Cochrane Library, Wanfang, CNKI, and VIP were searched, and the relevant data was extracted, including media progression-free survival (mPFS), media overall survival (mOS), and grade 3/4 adverse events (AEs).
RESULTS
We included 4 randomized controlled trials (RCTs), 2 RCTs showed that metronomic maintenance chemotherapy could significantly improve mPFS compared to observation group; another RCT showed that metronomic maintenance chemotherapy group did not have low mPFS than the bevacizumab maintenance treatment (MT). The final RCT showed that dual-agent metronomic chemotherapy combined with bevacizumab MT did not improve mPFS compared with bevacizumab MT. The 3 RCTs showed that the metronomic maintenance therapy could not effectively improve mOS in mCRC compared to observation group or bevacizumab MT, while another RCT reported that the mOS in metronomic maintenance chemotherapy group was similar to bevacizumab MT. AEs was mostly mild and manageable. Grade ≥ 3 AEs are mostly nonhematological toxicity, and no deaths related to AEs were reported.
CONCLUSION
This systematic review indicates that metronomic chemotherapy for mCRC MT can improve mPFS in some patients and is relatively safe. However, improvements in OS in most RCTs are arguable. Therefore, we need further studies to verify its long-term efficacy.
Topics: Humans; Bevacizumab; Colorectal Neoplasms; Randomized Controlled Trials as Topic; Colonic Neoplasms; Rectal Neoplasms; Lymphoma, Follicular
PubMed: 36401426
DOI: 10.1097/MD.0000000000031659 -
Geburtshilfe Und Frauenheilkunde May 2016Conventional chemotherapy is generally administered in high doses followed by a treatment-free period to give the body needful time to recover. This "maximum tolerated... (Review)
Review
Conventional chemotherapy is generally administered in high doses followed by a treatment-free period to give the body needful time to recover. This "maximum tolerated dose" approach results in high response rates. However, long periods between therapy cycles can lead to development of resistance mechanisms and consequently disease progression. One of the most interesting alternative strategies is metronomic chemotherapy. This concept relies on the continuous administration of chemotherapy at low doses and aims at targeting endothelial cells in the tumor bed as well. Recently, metronomic chemotherapy has been incorporated into the recommendations issued by the German AGO expert panel (www.ago-online.de). A systematic review of PubMed/Medline, ClinicalTrials.gov, the European Clinical Trials Database (EudraCT) and the Cochrane Database was conducted. In the present review, we discuss the current evidence on metronomic chemotherapy in metastatic breast cancer.
PubMed: 27239061
DOI: 10.1055/s-0042-105871 -
European Journal of Cancer (Oxford,... Nov 2013Low-dose metronomic (LDM) chemotherapy, the frequent and continuous use of low doses of conventional chemotherapeutics, is an emerging alternative to conventional... (Meta-Analysis)
Meta-Analysis Review
Low-dose metronomic (LDM) chemotherapy, the frequent and continuous use of low doses of conventional chemotherapeutics, is an emerging alternative to conventional chemotherapy. While promising tumour control rates and excellent safety profiles have been observed, there are no definitive phase III trial results. Furthermore, the selection of patients, drug dosages and dosing intervals is empirical. To systematically review the current state of knowledge regarding LDM chemotherapy, we searched the MEDLINE, EMBASE, CENTRAL and PubMed databases for fully published LDM chemotherapy trials. We calculated the relative dose-intensity (RDI, mg/m(2)/week) of each LDM regimen as compared to conventional maximum tolerated dose (MTD) dosages and the 'dosing-density' (DD, % of days with chemotherapy administration per cycle). Meta-regression was performed to examine factors associated with disease control rate (DCR; complete response (CR)+partial response (PR)+stable disease (SD)). Eighty studies involving mainly pretreated patients with advanced/metastatic breast (26.25%) and prostate (11.25%) cancers were retrieved. The most commonly used drug was cyclophosphamide (43%). LDM chemotherapy was frequently combined with other therapies (64.5%). Response rate (RR) and progression-free survival (PFS) were the most frequent primary end-points (24% and 19%). Mean RR was 26.03% (95% confidence interval (CI): 21.4-30.7), median PFS was 4.6months (interquartile range (IQR): 2.9-7.0) and mean DCR was 56.3% (95% CI: 50.9-61.6). RDI, DD and metronomic drug used were not associated with DCR. Grade 3/4 adverse events were rare (anaemia 7.78%, fatigue 13.4%). Thus, LDM therapy appears to be clinically beneficial and safe in a broad range of tumors. However, meta-regression analysis did not identify predictive factors of response.
Topics: Administration, Metronomic; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Disease Progression; Disease-Free Survival; Female; Humans; Male; Prostatic Neoplasms; Remission Induction; Time Factors; Treatment Outcome
PubMed: 23880474
DOI: 10.1016/j.ejca.2013.06.038 -
Cancer Treatment Reviews Sep 2014Metronomic therapy (MT) refers to repetitive, low doses of chemotherapy drugs. MT exerts an effect not only on tumour cells, but also on their microenvironment. In... (Review)
Review
Metronomic therapy (MT) refers to repetitive, low doses of chemotherapy drugs. MT exerts an effect not only on tumour cells, but also on their microenvironment. In particular, the low-dose schedule compromises the repairing process of endothelial cells, leading to an anti-angiogenic effect. In addition to the anti-angiogenic effect, MT could have an immunological action through the restoration of the anticancer effect of the immune system and induction of tumour dormancy. Consequently the association of targeted therapy with anti-angiogenic properties or specific immunologic drugs could enhance the efficacy of MT. During the past 15 years, several studies have been published evaluating the metronomic strategy in breast cancer. We conducted a systematic review of the results of phase I, II and III studies testing MT in breast cancer patients. The analyses included the efficacy and toxicity data of MT, and the future development of this strategy in breast cancer are also discussed. The systematic review presented here suggests that MT is a treatment option for breast cancer patients, has a low toxicity profile, efficacy in most patients and has potentially significant cost-effective advantages for public health.
Topics: Administration, Metronomic; Antineoplastic Agents; Breast Neoplasms; Female; Humans
PubMed: 24998489
DOI: 10.1016/j.ctrv.2014.06.002 -
Future Oncology (London, England) May 2016Endocrine treatment is the first-line therapy in hormone-sensitive metastatic breast cancer while chemotherapy is the first option in tumors refractory to endocrine... (Review)
Review
Endocrine treatment is the first-line therapy in hormone-sensitive metastatic breast cancer while chemotherapy is the first option in tumors refractory to endocrine therapy and in hormone-negative disease. Optimal duration, efficacy and safety of a maintenance endocrine therapy or chemotherapy after an induction treatment are still a matter of debate. We performed a literature review to identify studies regarding maintenance hormonal and chemotherapy treatments in metastatic breast cancer. We analyzed data relating to efficacy (improvement of progression-free survival and overall survival) and safety (symptoms relief and quality of life [QoL]). Maintenance endocrine therapy could prolong progression-free survival with a better control of symptoms and improving QoL. Maintenance chemotherapy prolong the response to a previous treatment, worsening the QoL, except for metronomic capecitabine.
Topics: Antineoplastic Agents; Antineoplastic Agents, Hormonal; Breast Neoplasms; Disease-Free Survival; Female; Humans; Maintenance Chemotherapy; Quality of Life
PubMed: 26996100
DOI: 10.2217/fon-2015-0065 -
Geburtshilfe Und Frauenheilkunde Feb 2017Conventional chemotherapy is based on the "maximum tolerated dose" principle and aims at administering high doses of cytotoxic drugs followed by a rest period necessary...
Conventional chemotherapy is based on the "maximum tolerated dose" principle and aims at administering high doses of cytotoxic drugs followed by a rest period necessary for the body to recover. In the last decades alternative strategies have been developed to avoid serious side effects of conventional treatment, among them the metronomic chemotherapy. Much like a metronome keeps steady rhythm, metronomic therapy is administered continuously in low doses for a long time. In metastatic breast cancer, metronomic therapy is a valid option in pretreated or vulnerable patients and its use has recently been incorporated into various guidelines. In early breast cancer, the role of metronomic treatment remains to be clarified. A systematic review of PubMed/MEDLINE, ClinicalTrials.gov, the European Clinical Trials Database (EudraCT) and the Cochrane Database was conducted. In the present review, we discuss the current evidence on metronomic chemotherapy in non-metastatic breast cancer.
PubMed: 28331236
DOI: 10.1055/s-0043-100388 -
Acta Oncologica (Stockholm, Sweden) Jul 2020Metronomic dosing is used to give continuous chemotherapy at low doses. The low doses have minimal side effects and may enable cancer treatment to be remodeled toward...
Metronomic dosing is used to give continuous chemotherapy at low doses. The low doses have minimal side effects and may enable cancer treatment to be remodeled toward the management of chronic disease. We searched PubMed database to obtain relevant clinical trials studying metronomic chemotherapy (MCT). Our main focus was to find controlled phase II and phase III trials. This systematic review summarizes the results of 91 clinical reports focusing on randomized phase II and phase III clinical studies between 2012 and 2018. During that time, nine randomized phase II and 10 randomized phase III studies were published. In the majority of the studies, MCT was well tolerated, and major side effects were rarely seen. Altogether, 4 phase III studies and 4 randomized phase II studies presented positive results and some clinical benefit. Most of the studies did not show significantly improved overall survival or progression-free survival. Typically, the metronomic dosing was explored in a maintenance setup and was added to other agents given within normal high doses, whereas no trial was performed challenging metronomic dosing and best supportive care in later treatment lines. Therefore, there is no definite evidence on the efficacy of single metronomic dosing and firm evidence of metronomic dosing is still missing. There is a need for further confirmation of the usefulness of this approach in clinical practice.
Topics: Administration, Metronomic; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Humans; Neoplasms; Progression-Free Survival; Randomized Controlled Trials as Topic; Survival Rate
PubMed: 32275176
DOI: 10.1080/0284186X.2020.1744719 -
East African Medical Journal Sep 2005Strategies to circumvent or lessen the myelotoxicity associated with combination chemotherapy may improve the overall outcome of the management of patients particularly... (Review)
Review
BACKGROUND
Strategies to circumvent or lessen the myelotoxicity associated with combination chemotherapy may improve the overall outcome of the management of patients particularly in resource poor settings.
OBJECTIVES
To develop effective non-myelotoxic therapies for Burkitt's Lymphoma (BL) and AIDS-related non-Hodgkin's lymphoma.
DATA SOURCES
Publications, original and review articles, conference abstracts searched mainly on Pubmed indexed for medline.
DATA EXTRACTION
A systematic review of the clinical problem of combination chemotherapy. Identification of clinical strategies that circumvent or lessen the myelotoxicity of combination cytotoxic chemotherapy. Length of survival, lack of clinically significant (> grade 3) myelosuppression and weight loss were used as markers of myelotoxicity.
DATA SYNTHESIS
Review of published experience with some of these strategies including dose-modification of multi-agent chemotherapy; rationale for targeted therapies, and the preclinical development of a mouse model exploring the role of metronomic scheduling substantiate pragmatism and feasibility of these approaches.
CONCLUSION
Myelotoxic death rates using multi-agent induction chemotherapy approach 25% for endemic Burkitt's lymphoma and range between 20% to 60% for AIDS-related malignancy. This is mostly explained by the paucity of supportive care compounded by wasting and inanition attributable to advanced cancer and HIV infection making patients more susceptible to myelosuppressive side effects of cytotoxic chemotherapy. Investigations and alternative approaches that lessen or circumvent myelotoxicity of traditional cytotoxic chemotherapy for the management of Burkitt's lymphoma and AIDS-related non-Hodgkin's lymphoma in the resource-constrained setting are warranted. Pertinent pre-clinical and clinical data are emerging to support the need for abrograting the myelosuppressive effects of traditional cytotoxic chemotherapy. This can be achieved by developing targeted anti-viral and other strategies, such as the use of bryostatin 1 and vincristine, and by developing a preclinical mouse model to frame the clinical rationale for a pilot trial of metronomic therapy for the treatment of Burkitt's and AIDS-related lymphoma. Implementation of these investigational approaches must be encouraged as viable anti-cancer therapeutic strategies particularly in the resource-constrained settings.
Topics: Antineoplastic Agents; Bryostatins; Burkitt Lymphoma; Drug Therapy, Combination; Humans; Lymphoma, AIDS-Related; Macrolides; Vincristine
PubMed: 16619692
DOI: 10.4314/eamj.v82i9.9388 -
Journal of Neuro-oncology Nov 2011Low grade gliomas (LGG) contribute to 50% of all central nervous tumors in children and 15% of all gliomas in adults. Temozolomide (TMZ) is an oral alkylating agent with... (Review)
Review
Low grade gliomas (LGG) contribute to 50% of all central nervous tumors in children and 15% of all gliomas in adults. Temozolomide (TMZ) is an oral alkylating agent with activity in high and LGG. Various regimens of TMZ are currently in use. We attempted to assess the impact of different TMZ regimens on the treatment of LGG. A systematic review of the literature identified all the studies published in Pubmed, EMBASE and Cochrane databases which met the inclusion criteria. The primary outcome measure was the impact of different TMZ regimens on the 12 month progression-free survival (PFS) rates of patients diagnosed with progressive LGG. Secondary outcome measures looked at the ability of the three regimens to elicit an objective response and the associated toxicity. Statistical pooling and calculation of weighted mean average of each proportion (WMAP) was conducted using a random-effects model. 18 studies (736 patients) were analyzed. PFS at 12 months revealed a WMAP of 0.61 (95% CI 0.44-0.78) for regimen A, 0.59 (0.28-0.89) for regimen B, and 0.91 (95% CI 0.83-0.99) for regimen C (Regimen A--200 mg/m(2)/day for 5 days, repeated every 4 weeks; B--75 mg/m(2)/day for 21 days repeated every 4 weeks; C--75 mg/m(2)/day for 7 weeks with 4 weeks of every 11 weeks). In terms of objective response, WMAP were 0.19 (95% 0.13-0.25), 0.27 (95% CI 0.15-0.39) and 0.21 (95% CI 0.10-0.32) for regimen A, B, C respectively. When analyzing hematological toxicity, WMAPs were 0.14 (95% 0.11-0.18), 0.35 (0.14-0.56) and 0.23 (95% CI 0.03-0.43). The bulk of evidence originates from the standard 5 day/month regimen A but with a lack of comparative studies. Analysis revealed significant heterogeneity. Although there is possibly an indication that metronomic regimens of TMZ result in better PFS and response rate when compared to the conventional standard 5 day regimen, insufficient available data and study heterogeneity preclude any safe conclusions. Well designed randomized controlled clinical trials are needed to establish the efficacy of metronomic regimens of TMZ in LGGs.
Topics: Adult; Antineoplastic Agents, Alkylating; Brain Neoplasms; Dacarbazine; Drug Administration Schedule; Glioma; Humans; Neoplasm Grading; Temozolomide
PubMed: 21748491
DOI: 10.1007/s11060-011-0657-7