Searching for “metronomic" in PubMed lead to the identification 99 publications in 2015. More publications on the topic including those using for instance the term “low dose chemotherapy” are therefore not included in this analysis.

The paediatric publications are very limited with only 7 papers published in 2015. Moreover, 4 are pre-clinical studies, one looked at angiogenic biomarkers during the maintenance of children with leukaemia and 3 are case reports.

Most of the publications deals directly with adult malignancies (68).

Interestingly, a growing part of the publications on metronomics are now clinical pieces with 41 publications in 2015. The majority are retrospective and small series (17) or case reports (7). Of note, 7 phases I, 12 phases II trials and most importantly 3 phase 3 trials have been published. Thus, Nasr and al reported that metronomic methotrexate and cyclophosphamide after carboplatin included adjuvant chemotherapy in triple negative breast cancer could lead to significant improvement in the survival and was well tolerated. (Nasr Ann Transl Med 2015). Elswhere, the Cairo 3 trials demonstrated that a Maintenance treatment with capecitabine plus bevacizumab after six cycles of CAPOX-B in patients with metastatic colorectal cancer is effective and does not compromise quality of life. (Simkens LH Lancet 2015). These phases 3 trials are important since the lack of successful phase III trials that demonstrate the usefulness of metronomic is frequently cited as a important breaks to the use of metronomic.

The lost frequently used anticancer agents in the mettronmic publication in 2015 are: cyclophosphomide (20), taxanes (10), vinorelbine (9), capecitabine/5FU (7) and temozolomide (7).

Metronomic chemotherapy is frequently used in combination with immunomodulators (8), anti-VEGF or TKI (13), drug repositioning (16) or as purely metronomic combinations (15). Among the combinations tested the combination of pazopanib and metronomic topotecan seems to have a good potential in many tumour types including paediatric malignancies.

There were also 19 reviews including 2 published in Nature Reviews Clinical Oncology.

34 publications were preclinical studies showing the sustained interested in metronomic chemotherapy from a scientific point of view with a growing interest in combining metronomic chemotherapy with immune therapies.