Pilot study of sodium phenylbutyrate as adjuvant in cyclophosphamide-resistant endemic Burkitt's lymphoma

Burkitt's lymphoma (BL) accounts for the majority of childhood malignancies seen in sub-Saharan Africa. In Malawi, cyclophosphamide (CPM), the mainstay of treatment for endemic BL, is effective in around 50% of cases. Evidence exists in support of an association between activation of replication of Epstein-Barr virus (EBV) in the tumour and response to this chemotheraupeutic agent. Phenylbutyrate (PB), approved for treatment of inborn errors of the urea cycle with minimal toxicity in children, induces EBV replication and cell lysis in BL-derived cell cultures. It has also shown some success as adjuvant in treatment of chronic leukaemia and lymphoma. We tested in African BL patients with CPM-resistant tumours, and thus unlikely to survive, the hypothesis that PB can reverse this resistance. A study of five patients showed PB before CPM to induce shrinkage of CPM-resistant tumours in two of them. Findings suggested that for this effect PB pre-treatment should be given for a week before CPM treatment. A larger study is indicated.