Metronomic therapy in pediatric oncology: A snapshot

Abstract

Metronomic chemotherapy transitioned from the bench to bedside in the early 2000s and since then has carved a niche for itself in pediatric oncology. It has been used solely or in combination with other modalities such as radiotherapy, maximum tolerated dose chemotherapy, and targeted agents in adjuvant, palliative, as well as maintenance settings. No wonder, the resulting medical literature is extremely heterogeneous. In this review, the authors review and synthesize the published literature in pediatric metronomics giving a glimpse of its history, varied applications, and evolution of this genre of chemotherapy in pediatric cancers. Limitations, future prospects, and grey areas are also highlighted.

Adapting Management of Sarcomas in COVID-19: An Evidence-Based Review

“…Oral metronomic therapy (a combination of thalidomide, celecoxib, cyclophosphamide and etoposide) has been found useful in non-bone sarcoma solid tumors with minimal toxicity [41,42], this may be a reasonable option in this…”

Metronomics in Pediatric Oncology: Lessons Learned and the Way Forward

“…[2,6,7] The empiricism of metronomic protocol dosages and dosing schedules, variable terminologies and vague definitions, absence of reliable biomarkers, and lack of large randomized Phase III trial and the lack of support by the pharmaceutical industry have added to the clinician's reluctance. [5] In our randomized controlled trial published in 2017 comparing a four-drug metronomic cocktail (thalidomide, cyclophosphamide, etoposide, and celecoxib) versus placebo in 108 patients of progressive pediatric solid tumors post 2 lines of chemotherapy, the metronomic regimen did not improve the 6-month progression-free survival (the primary endpoint) or overall survival. [8] However, in an unplanned subgroup analysis, the subgroup of nonbone sarcomas had a significant benefit, hinting that histology should be a major factor in choosing metronomics wisely.…”

“…As we move ahead in time, the studies get bigger and we get to Phase II single-arm studies. [5] Finally, after 2010, we begin to get some comparison with historical cohorts and then randomized trials. We also find a conspicuous change in the composition of the metronomic combinations; for example, vinblastine, fenofibrate, and Vitamin D are being explored.…”

Metronomic Chemotherapy in Pediatric Oncology: From Preclinical Evidence to Clinical Studies

“…The implementation of MC in pediatric oncology, alone or in combination with other approaches such as radiotherapy, MTD chemotherapy, immunotherapy, and targeted agents, has mostly adjuvant, palliative, and maintenance purposes [ 9 ].…”