Abstract
Purpose: This report seeks to validate some of the findings in animal models of cancer chemotherapy with observations in the real-world management of endemic Burkitt lymphoma in Nigerian children between 1979 and 1986.
Materials and Methods: Between 1979 and 1981, a period of relative affluence in Nigeria, children with Burkitt lymphoma were treated with an induction course of four 14-day cycles of combination regimens: vincristine 1.4 mg/m2 on day 1, cyclophosphamide 1000 mg/m2 on day 1, methotrexate 12.5 mg/m2 on day 2, 3 and 4, and intrathecal treatment with methotrexate 12.5/m2 or cytosine arabinoside 50mg/m2 on day 1 and day 5 of 4 cycles, followed by 4-6 28-day cycles as maintenance. By 1981-1983, socioeconomic challenges led to loss of treatment quality, including variability in dose intensity and duration. Between 1984 and 1986, the children were managed on a randomized phase II clinical trial, in which donated cytosine arabinoside at high doses, e.g., 1000mg/m2 IV q12 hours x 4 doses – was given, with the aim of overcoming physiological barrier for better control of central nervous system involvement.
Results: Chi-square test showed strong correlation between remission rate and dose intensity of single agents and mean relative dose intensity of combination chemotherapy (p< 0.0001), while Cox proportion hazard model revealed association between progression free survival and mean relative dose intensity (p = 0.0001) regardless of central nervous system involvement (p = 0.0003). Evaluation by log-rank test revealed highly significant association between less than 42, and more than 43 to 95 treatment days and progression free survival (p<0.0001), but, counterintuitively, not with more than 95 days (p=0.809). The clinical trial regimens led to complete plus partial response rates of 100% vs 45% and progression free survival rate of 64% vs 19.7% (p=0.205), and mean relative dose intensities of 592.2 vs 102.6 (p<0.0001) in the experimental and control arms, respectively.
Conclusion: The clinical manifestations of the disease as well as the treatment outcomes in correlation with treatment qualities reflect predictable observations in animal models, thus, confirming the relevance of adherence to the principles of chemotherapy in clinical practice.