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First Barton Kamen-MGHI prize : Modified COMBAT (Combined Oral Metronomic Biodifferentiating Antiangiogenic Treatment) therapy in poor prognosis pediatric malignant brain tumors

The first Barton Kamen-MGHI Prize has been attributed to Pr Shripad Banavali following the submission of the following abstract. The work will be presented during the 4th Metronomic Meeting that will take place in Milano on the 24th and 25th of June 2014. Dr Shripad D. Banavali is Professor & Head, Dept. of Medical & Pediatric Oncology Vice President (India), Asian Cellular Therapy Organization and Coordinator, TMC-Rural Outreach Program in Mumbai


CHINNASWAMY GIRISH, Prasad Maya, Vora Tushar, Arora Brijesh, Sridhar Eppari, Gupta Tejpal, Moiyadi Ali, Jalali Rakesh, Kukure Purna, Banavali Shripad

Background: The outcome of children with recurrent/high risk malignant brain tumors continues to be poor with conventional modalities of therapy. Metronomic therapy (COMBAT) has been found to be beneficial in many disseminated and aggressive pediatric solid tumors. We evaluated the impact (efficacy and toxicity) of this strategy in children with poor prognosis malignant brain tumors.

Methods: Children deemed to have a poor risk malignant brain tumor (by histology, site, metastatic status) were started on modified COMBAT regimen after completion of conventional therapy. Relapsed high grade tumors were also included. The treatment strategy consisted of the COMBAT regimen which includes low dose temozolomide, etoposide, sodium valproate and 13-cisretinoic acid administered in 12-weekly cycles. All children were followed up at 3 monthly intervals with clinical evaluation and MR imaging.

Results: Thirty four children were started on Modified COMBAT therapy between the year 2010-2013 and 32 were available for evaluation. The median age of the study population is 10 years with a male:female ratio being 2:1. Among the 32 patients, 13(40.6%) had relapsed/progressive medulloblastoma, 7(21.9%) had metastatic/recurrent PNET(supratentorial), 7(21.9%) had recurrent anaplastic ependymoma and 5(15.6%) were diagnosed with diffuse pontine glioma. 23/32 (71%) of patients showed a response(SD/PR/CR) to therapy while 9(28%) of patients continued to progress with no response documented. Toxicity included grade III/IV cytopenia in 2 patients and 1 patient developed myelodysplastic syndrome. Isotretinoin skin toxicity was noted in majority and was manageable with topical interventions. In the final analysis 62.5%(20) of patients had progressed with median time to progression being 9 months (2-44 months) while 37.5%(12) patients had shown a positive sustained response.

Conclusion: The modified COMBAT regimen is a feasible, well tolerated and effective treatment option for children with high risk or metastatic brain tumours. The data is a retrospective analysis and hence a prospective study to evaluate this strategy systematically is warranted.