Prednisone, etoposide, procarbazine, and cyclophosphamide (PEP-C) oral combination chemotherapy regimen for recurring/refractory lymphoma: low-dose metronomic, multidrug therapy

BACKGROUND: Many patients with recurrent lymphoma are unable to tolerate intensive therapies, or have disease that is refractory. Metronomic chemotherapy offers a novel, potentially less toxic yet effective treatment strategy. METHODS: An analysis was performed on 75 lymphoma patients who were treated with the PEP-C regimen at a single institution. The program consisted of oral prednisone 20 mg after breakfast, cyclophosphamide 50 mg after lunch, etoposide 50 mg after dinner, and procarbazine 50 mg at bedtime with an oral antiemetic. All medications were administered daily until the white blood cell count fell to less than 3.0 x 10(9)/L, whereupon treatment was withheld until recovery from the nadir. Therapy was then reinstituted on a daily, alternate day, or fractionated weekly basis (eg, 5 of 7 days), depending on patient tolerance. Doses given per day were held constant. RESULTS: Eighty percent of patients had previously received 2 or more treatments. Overall, 69% achieved an objective response after PEP-C treatment, with 36% complete responses and 33% partial responses. Subjects with indolent histologies had superior overall responses, complete responses, and time on therapy relative to those with aggressive histologies. The regimen was generally well tolerated. CONCLUSIONS: Metronomic therapy with low-dose oral agents administered in combination for continuous, prolonged periods with minimal drug-free intervals represents a novel, active, easily tolerated approach to management of patients with recurrent lymphoma, particularly those with indolent histologies.