High dose intensity doxorubicin in aggressive non-Hodgkin's lymphoma: A literature-based meta-analysis

Background: Aggressive non-Hodgkin's lymphoma (NHL) represents ~60% of lymphomas in the West and even more in the developing world. cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) is recognized as the standard chemotherapy regimen and the addition of rituximab to B-cell subtypes has been shown to significantly improve treatment outcomes. Nevertheless, still a significant fraction of patients is not offered rituximab due to economic reasons. Thus, CHOP is still offered to these patients as well as those with T-cell subtypes. Data from the early 1990s have indicated that the dose intensity (DI) of doxorubicin is a key factor in predicting survival. Methods: A Medline and Cochrane library search was carried out using the search terms 'CHOP', 'lymphoma' and 'randomized trials'. Eligible trials had CHOP as a control arm and any regimen administering doxorubicin at a higher DI (16.6 mg/m²/week) as the investigational arm. Pooling of data was carried out using the mixed effect model. Results: Eight trials were eligible. Patients receiving DI doxorubicin-based regimens had a significantly better overall survival [summary hazard ratio (SHR) 0.82; 95% confidence interval (CI) 0.71-0.96], event-free survival (SHR 0.86; 95% CI 0.75-0.99) and higher complete response rate (summary odds ratio 0.91; 95% CI 0.67-0.97). Conclusion: High DI doxorubicin based should be considered in patients with aggressive NHL.