Next generation metronomic chemotherapy—report from the Fifth Biennial International Metronomic and Anti-angiogenic Therapy Meeting, 6–8 May 2016, Mumbai

Abstract

The 5th Biennial Metronomic and Anti-angiogenic Therapy Meeting was held on 6th – 8th May in the Indian city of Mumbai. The meeting brought together a wide range of clinicians and researchers interested in metronomic chemotherapy, anti-angiogenics, drug repurposing and combinations thereof. Clinical experiences, including many from India, were reported and discussed in three symposia covering breast cancer, head and neck cancers and paediatrics. On the pre-clinical side research into putative mechanisms of action, and the interactions between low dose metronomic chemotherapy and angiogenesis and immune responses, were discussed in a number of presentations. Drug repurposing was discussed both in terms of clinical results, particularly with respect to angiosarcoma and high-risk neuroblastoma, and in pre-clinical settings, particularly the potential for peri-operative interventions. However, it was clear that there remain a number of key areas of challenge, particularly in terms of definitions, perceptions in the wider oncological community, mechanisms of action and predictive biomarkers. While the potential for metronomics and drug repurposing in low and middle income countries remains a key theme, it is clear that there is also considerable potential for clinically relevant improvements in patient outcomes even in high income economies.

Immunogenic chemotherapy: Dose and schedule dependence and combination with immunotherapy

“…Cytotoxic cancer chemotherapeutic drugs are typically administered on a maximum tolerated dose (MTD) schedule, which may induce high host toxicity and can lead to tumor vasculature regrowth and selection of drug-resistant cell populations during the prolonged drug-free breaks required to recover from host toxicity [53]. In contrast, metronomic treatment schedules [54–57] deliver chemotherapeutic drugs at a lower dose than traditional MTD chemotherapy, but on a more frequent, or even a continuous (daily) schedule with less overall toxicity to the host. Several preclinical studies have investigated the impact of these and other treatment schedules on the strength and duration of immune anti-tumor responses.…”

Metro‐SMHOP 01: Metronomics combination with cyclophosphamide‐etoposide and valproic acid for refractory and relapsing pediatric malignancies

“…A randomized trial would be mandatory to answer this question. Alternative repurposed drugs could be used to further strengthen and widen the spectrum of action of a metronomic combination or be selected on the biomolecular profiling of the tumor, 24,25 with the advantages of usually mild toxicity and low cost while trying to tailor a metronomic regimen. 14 For low-and middle-income countries, metronomics has been foreseen as a potential way to overcome many barriers to anticancer treatment such as cost and toxicities.…”

“…14 For low-and middle-income countries, metronomics has been foreseen as a potential way to overcome many barriers to anticancer treatment such as cost and toxicities. 4 Over the last few years, a growing number of publications have investigated the potential role of metronomics for children in LMIC, 4,14,20,24,[26][27][28] and a recent international survey has confirmed the interest of pediatric oncologists working in LMIC for this approach, especially for palliative care or as a maintenance for patients with high-risk disease. 29 Indeed, access to newer therapies such as targeted therapies or immunotherapies is very limited in LMIC.…”

Metronomic therapy in pediatric oncology: A snapshot

“…Experts from developed and developing low‐ and middle‐income countries have joined hands in serial International Workshops of Metronomics conducted by Metronomic Global Health Initiative (metronomic.org) …”