Intensification of the CHOEP Regimen for High-Grade Non- Hodgkin’s Lymphoma by G-CSF: Feasibility of a 14-Day Regimen

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Abstract
Background: The efficacy of chemotherapy protocols for the treatment of high-grade non-Hodgkin’s lymphoma (NHL) has not improved significantly during the last decade. Treatment results in patients presenting with high-grade NHL are not satisfactory. At present, etoposide remains the only drug that may add to the efficacy of the CHOP regimen. Hemopoietic growth factors like G-CSF allow a dose intensification of effective chemotherapy regimens by shortening the time of neutro-penia and allowing earlier application of subsequent cycles. We have initiated a phase I/II trial of CHOP + etoposide (CHOEP) applied in 14-day intervals with G-CSF support to test the feasibility of this regimen before starting a trial comparing its efficacy with the more conventional regimens. Patients and Methods: Patients with high-grade NHL according to the Kiel classification were treated with the CHOEP-14 regimen, consisting of cyclophosphamide (750 mg/m2 i.v., day 1), doxorubicin (50 mg/m2, day 1), vincristine (2 mg i.v., day 1), etoposide (100 mg/m2, days 1-3) and prednisolone (100 mg p.o., days 1-5). G-CSF, 300 μg (up to 75 kg body weight) or 480 μg was applied s.c. (days 4-13). Cycles were repeated on day 15 and patients received 6 cycles followed by irradiation of bulky disease with 36 Gy. Results: To date, 30 patients with high-grade NHL (median age 55 years, range 25-79 years) have been treated for a total of 159 evaluable chemotherapy cycles. 24 patients have finished 6 cycles each, and 20 patients are evaluable for response. Application of the following cycle was on day 15 in 146/159 cycles, and delay in 16 cycles (duration between 1 and 13 days) was not caused by ncutro-penia in any patient. Leucopenia Conclusion: Dose intensification of the standard CHOP regimen by addition of etoposide and implementation of 14-day cycles with growth factor support is possible without undue increase in treatment toxicity. A randomized multicenter phase III trial has been initiated to test whether this significant increment in dose intensity translates into increased remission rates and/or longer remission durations.

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