We have just analyzed the number and type of publications about metronomic chemotherapy indexed in the Thomson Reuters Web of Knowledge database from 2000 to 2011. 2000 was the year of the 2 first pre-clinical papers form the team of Judah Folkman and Robert Kerbel reporting about the potential of low dose anti-angiogenic chemotherapy were published. Following these 2 papers, Douglas Hanaghan introduced the term metronomic the very same year. We searched in the Thomson Reuters Web of Knowledge database all articles using the key word "metronomic". All non-relevant articles (outside of the field of oncology) and abstracts from conferences and/or meeting were excluded. Then, articles were classified as review, editorial, letter to the editor, preclinical work or clinical work. It is important to note that articles using the term “low doses” or “oral” that were commonly used for etoposide or cyclophosphamide are therefore not included in the analysis. Similarly all the literature about maintenance therapy for leukemia that relies on metronomic purinethol and methotrexate is absent. Overall, we identified 593 publications from 2000 to 2011. Details about the number and type of publications can be found in the figure 1. There is a clear increase in the number of publication since 2000 with a total number of publications per year ranging from 4 in 2000 to 102 in 2010.
There is an important number of reviews which constitute almost 20% of the metronomic publications. Preclinical and clinical studies represent each roughly 30% of the publications. The percentage of paediatric publication is rather limited with 8% of the total. Among these, half of the publications are clinical studies or cases report. There are only 8 preclinical work dedicated to the filed of paediatric.
Of note, within 11 years there are only 3 publications that deal with metronomic chemotherapy in developing countries. One of these publications is the Metro-Mali01 by Fousseyni Traore and the second an editorial that accompanied the publication of MetroMali. Hopefully, the number of papers reporting the use of metronomic in low or middle income countries, may increase since in 2012, there are already two publications from the Tata Memorial Institute in Mumbay.
Klement, G, et al. Continuous low-dose therapy with vinblastine and VEGF receptor-2 antibody induces sustained tumor regression without overt toxicity. J Clin Invest 2000. 105:R15-R24
Browder, T, et al. Antiangiogenic scheduling of chemotherapy improves efficacy against experimental drug-resistant cancer. Cancer Res 2000. 60:1878-1886.
Hanahan, D, and al. Less is more, regularly: metronomic dosing of cytotoxic drugs can target tumor angiogenesis in mice J Clin Invest. 2000;105:1045–1047
Fousseyni, T et al. Children treated with metronomic chemotherapy in a low-income country: METRO-MALI-01. J Pediat Hemato Oncol 2011 ; 33 : 31-34
Klement, GL, et al. Nontoxic, Fiscally Responsible, Future of Oncology: Could it be Beginning in the Third World? J Pediatr Hematol Oncol. 2011; 33:1-3.
Sondhi, V, et al. Complete Remission and Long-term Survival in a Child With Relapsed Medulloblastoma With Extensive Osteosclerotic Bony Metastasis With a Novel Metronomic Chemobiological Approach. J Pediatr Hematol Oncol. 2012 Jan 16. [Epub ahead of print]
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