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.
Highlights
The meeting was organised such that the first day (Friday 6th May) was devoted to an extended workshop on clinical trial design and translational research for metronomic studies, whereas days two and three included a series of plenary talks, symposia on specific disease areas and other presentations
Turning to the issue of resistance or relapse after metronomic chemotherapy (MC), analysis of breast cancer patients treated with metronomic cyclophosphamide and capecitabine with fortnightly bevacizumab showed that relapse was associated with an increase in VEGF-A and low circulating peripheral blood endothelial cells (CECs) counts, possibly suggestive of a switch to an alternative form of tumour vascularisation [46]
There remains a good deal of active research to further elucidate the mechanisms of action of MC, with respect to anti-angiogenesis, the immune response and direct effects on cancer cells
Summary
The meeting was organised such that the first day (Friday 6th May) was devoted to an extended workshop on clinical trial design and translational research for metronomic studies, whereas days two and three included a series of plenary talks, symposia on specific disease areas and other presentations. Despite more than a decade of clinical studies, very little work has been published on the PK data related to low-dose chemotherapy, primarily due to an underestimation of the importance of plasma/tumour concentrations of drugs and their biological effects This is the case when there are multiple mechanisms of action for MC, and that these may be operative at different drug concentrations [2]. Forget et al had retrospectively analysed data from surgical breast cancer patients treated with different forms of analgesia and had shown that pre-surgical treatment with ketorolac was associated with a statistically significant reduction in the rate of recurrence [8] Another example is cimetidine, a well-known antacid with a range of posited anticancer properties [9,10]. The case was made for a number of possible peri-operative trials in different cancers, including a trial of pre-operative ketorolac in osteosarcoma
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