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High-dose intense doxorubicin-based regimens in aggressive non-Hodgkin's lymphoma: A systematic overview.

e19528 Background: Aggressive non-Hodgkin's lymphoma represents around 60% of lymphomas in the Western world and even more in Egypt. CHOP has been long been recognized as the standard chemotherapy regimen in this disease. The addition of rituximab (R) to CHOP in the treatment of B-cell subtypes has resulted in a significant improvement in all treatment endpoints. Nevertheless, still a significant fraction of patients in the developing world are not offered R due to economical reasons. Thus CHOP is still offered to these patients as well as those with T-cell subtypes. Data from the early 1990s have suggested that the dose intensity (DI) of doxorubicin may have a prognostic value. Hence we conducted a metaanalysis on chemotherapy regimens incorporating higher DI doxorubicin and compare them to CHOP in terms of complete response (CR) rate, event free survival (EFS) and overall survival (OAS).


METHODS
A MEDLINE and COCHRANE library search was performed using the search terms 'CHOP', 'lymphoma' and 'randomized trials'. Eligible trials were randomized trials, having CHOP as a control arm and any chemotherapy regimen administering doxorubicin at a higher DI than that of CHOP (16mg/m2/week) as the investigational arm. Pooling of data was performed using the mixed effect model. The outcome measure for pooling the CR rate was the odds ratio (OR) while the hazard ratio (HR) was the outcome measure for EFS and OAS. Confidence intervals were estimated according to the method developed by Parmar.


RESULTS
Eight trials published until February 2008 met the inclusion criteria. They included 3,668 patients randomly assigned to either CHOP (1,660 patients) or DI doxorubicin-based regimen (2008 patients). Patients receiving DI doxorubicin-based regimen had a significantly better overall survival (HR; 0.79; 95% CI: 0.66-0.94). As for the EFS and CR analyses, there was a trend in favor of patients who received the DI regimens; however the difference was not statistically significant (HR: 0.86; 95% CI: 0.71-1.03 & OR: 0.8; 95% CI: 0.63-1.02 respectively).


CONCLUSIONS
High DI doxorubicin-based regimens are associated with a better OAS compared to CHOP. Such approach should be considered in patients with aggressive B-cell lymphomas not offered R as well as those with T-cell lymphomas. No significant financial relationships to disclose.