Metronomic reloaded: Theoretical models bringing chemotherapy into the era of precision medicine.

@article{Benzekry2015MetronomicRT,
  title={Metronomic reloaded: Theoretical models bringing chemotherapy into the era of precision medicine.},
  author={S. Benzekry and E. Pasquier and D. Barbolosi and B. Lacarelle and F. Barlesi and N. Andr{\'e} and J. Ciccolini},
  journal={Seminars in cancer biology},
  year={2015},
  volume={35},
  pages={
          53-61
        }
}
Oncology has benefited from an increasingly growing number of groundbreaking innovations over the last decade. Targeted therapies, biotherapies, and the most recent immunotherapies all contribute to increase the number of therapeutic options for cancer patients. Consequently, substantial improvements in clinical outcomes for some disease with dismal prognosis such as lung carcinoma or melanoma have been achieved. Of note, the latest innovations in targeted therapies or biotherapies do not… Expand
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References

SHOWING 1-10 OF 75 REFERENCES
Metronomics: towards personalized chemotherapy?
TLDR
This Review comprehensively discusses the latest clinical data obtained from studies performed in both adult and paediatric populations, and highlights ongoing clinical trials of metronomic chemotherapy. Expand
Metronomic chemotherapy: new rationale for new directions
TLDR
The latest clinical trials of metronomic chemotherapy in adult and pediatric cancer patients and potential new mechanisms of action, such as restoration of anticancer immune response and induction of tumor dormancy are discussed. Expand
Metronomics chemotherapy: time for computational decision support
TLDR
This review covers the latest clinical trials investigating on metronomic vinorelbine and proposes alternative strategies for developing computational decision support to make metronomics a scientific-grounded strategy, rather than an empirical practice at the bedside. Expand
Minimizing long-term tumor burden: the logic for metronomic chemotherapeutic dosing and its antiangiogenic basis.
TLDR
It is demonstrated that the minimization of total tumor burden, rather than complete eradication, may often be the more practical objective, and that regularly spaced, "metronomic" dosing is the best way to achieve it. Expand
Less is more, regularly: metronomic dosing of cytotoxic drugs can target tumor angiogenesis in mice.
TLDR
Two studies suggest a potentially complementary strategy of rescheduling the administration of classical cytotoxic drugs in order to target tumor endothelial cells, and each presents data suggesting that “metronomic” dosing regimens—either continuous infusion or frequent administration without extended rest periods—could have real value in the clinic. Expand
A systematic literature analysis of correlative studies in low-dose metronomic chemotherapy trials.
TLDR
This work searched the MEDLINE, EMBASE, CENTRAL and PubMed databases for correlative studies conducted as part of LDM chemotherapy trials in order to identify the most promising biomarker candidates and found angiogenesis-related biomarkers were most commonly studied. Expand
Personalized medicine in oncology: where have we come from and where are we going?
TLDR
There is a persistent gap between the growing number of identified deregulated pathways or genetic mutations, both at the tumor and the constitutional levels, and their actual implementation at the bedside as part of clinical routine. Expand
Intermittent metronomic drug schedule is essential for activating antitumor innate immunity and tumor xenograft regression.
TLDR
This study demonstrates the critical importance of drug schedule: CPA induced a potent antitumor innate immune response and tumor regression when administered intermittently on a 6-day repeating metronomic schedule but not with the same total exposure to activated CPA administered on an every 3-day schedule or using a daily oral regimen. Expand
Maximum tolerated dose versus metronomic scheduling in the treatment of metastatic cancers.
TLDR
Simulation results reveal differences between primary tumor reduction and control of metastases but overall suggest use of the metronomic protocol. Expand
Dose-intensified treatment of diffuse large B-cell lymphomas
TLDR
D dose dense modifications improved the outcome of young and elderly patients with aggressive lymphomas compared to baseline CHOP-21, and the role of intensified rituximab within such approaches was determined. Expand
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