Bezafibrate and medroxyprogesterone acetate in resistant and relapsed endemic Burkitt lymphoma in Malawi; an open-label, single-arm, phase 2 study (ISRCTN34303497)

Endemic Burkitt’s lymphoma (eBL) accounts for half of childhood cancers where malaria is holoendemic. Limited healthcare resources preclude intensive chemotherapy, restricting cure rates to <50% versus >90% for children in high income countries. Our laboratory studies showed Bezafibrate and Medroxyprogesterone acetate (BaP) had potent anti-eBL activity and thus might provide affordable, non-toxic therapy. 95 children with resistant or relapsed eBL were recruited to receive BaP as an adjunct to local standard non-intensive rescue chemotherapy. Progesterone at doses used to treat testicular cancer, was combined with Bezafibrate at standard dose for familial hypercholesterolaemia and then at 6 and 12x that dose to achieve equivalence to the laboratory defined optimum BaP concentrations. No significant toxicity was attributable to BaP alone or in combination with chemotherapy. 61 patients received BaP therapy alone for the first week before addition of chemotherapy. In that time, in only 7 patients (all on low dose BaP) did lymphoma size increase in which case chemotherapy was started early. In 33 patients lymphoma growth halted and in 15 patients, tumours shrank during BaP therapy alone. At end of all therapy clinical complete remissions were present in 41%, 43% and 66% of low, intermediate and full dose BaP, respectively, (p=0.03).