High-Dose Cytosine Arabinoside Chemotherapy of Burkitt Lymphoma:Advocating Sustainable Strategies for Capacity Building in Systemic CancerCare in Nigeria
2015
Abstract Background: Major factors of treatment failure in Burkitt lymphoma (BL) in Nigerian children include drug resistance and the central nervous system (CNS) “sanctuary effect”. A phase II randomized trial of high-dose cytosine arabinoside was designed to address both problems. Materials and methods: Children with advanced BL, with or without CNS involvement, seen at the University College Hospital, Ibadan, Nigeria from 1984 to1985, and with life expectancy of at least one month, were randomized to an investigational (R-I) treatment regimen of cyclophosphamide (CTX) 1000 mg/m2 IV day 1, Vincristine (VCR) 2·0 mg/m2 IV day 1, cytosine arabinoside (AC) 50 mg/m2 q12hr × 6 doses in cycles 1 and 4, and 1000 mg/m2 q12hr × 4 doses and 50 mg/m2 q12hr × 2 doses for cycles 2 and 3 cycles q14days × 4cycles; or a standard regimen (R II) of CTX 1000 mg/m2 IV day 1, VCR 2·0 mg/m2 IV day 1, AC 50 mg/m2 q12hr × 6 doses q14days × 4 cycles. AC 50 mg/m2 was given intrathecally on days 1 and 5 of each cycle. Results: Complete remission rate (CR) in R-I vs R-II was 9/9 (100%) vs 6/11 (54.5%), partial response 0/9 vs 4/11 (36·4%), non-response 0/9 vs 1/11 (9·1%) and probability of overall survival (OS) 64% vs 19%. Challenges encountered then, including manpower inadequacies and unreliable drug supply continue to impact management of BL three decades later as reported from 10 Nigerian institutions between 1984 and 2014, with cost related, public health support, and manpower deficiencies resulting in poor outcomes (CR<35%, and OS< 5%). Conclusion: HDAC overcomes drug resistance and CNS sanctuary effect in BL and could serve as basis for cancer chemotherapy research in sub-Sahara Africa, provided cultural deficiencies are addressed.
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