Another means of intensifying CHOP is the use of infusional administration. Infusional regimens are based on the premise that prolonged exposure of anti-neoplastic agents breeds less drug resistance as compared to brief, but higher, doses of chemotherapy. The infusional regimen EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, adriamycin) is highly active in aggressive lymphomas. It was first tested in a group of relapsed and refractory patients, all of whom had failed front-line CHOP-like regimens.47 Despite the fact that all patients had previously received these same agents, the overall response rate exceeded 70% in patients with aggressive lymphomas. Furthermore, the authors discovered significant variability in serum drug concentrations between patients. This formed the basis for their subsequent investigation of dose-adjusted EPOCH (DA-EPOCH) in which chemotherapy drug doses are escalated or de-escalated each cycle based on the neutropenic nadir and neutropenic duration during the previous cycle; this type of patient-specific therapy could theoretically allow maximal use of each agent. In a group of 49 evaluable patients with previously untreated DLBCL, 92% achieved a complete response, and there was a PFS of 70% and OS of 73% at 5 years.48 Most recently, the addition of rituximab to DA-EPOCH was tested in a cooperative group setting. DA-EPOCH-R will be the investigational arm in a large, randomized, prospective Cancer and Leukemia Group B study for advanced lymphoma.
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