INTENSIFICATION OF THE CHOEP REGIMEN FOR HIGH-GRADE NON-HODGKINS-LYMPHOMA BY G-CSF - FEASIBILITY OF A 14-DAY REGIMEN

Background: The efficacy of chemotherapy protocols for the treatment o f high-grade non-Hodgkin's lymphoma (NHL) has not improved significant ly during the last decade. Treatment results in patients presenting wi th high-grade NHL are not satisfactory. At present, etoposide remains the only drug that may add to the efficacy of the CHOP regimen. Hemopo ietic growth factors like G-CSF allow a dose intensification of effect ive chemotherapy regimens by shortening the time of neutropenia and al lowing earlier application of subsequent cycles. We have initiated a p hase I/II trial of CHOP + etoposide (CHOEP) applied in 14-day interval s with G-CSF support to test the feasibility of this regimen before st arting a trial comparing its efficacy with the more conventional regim ens. Patients and Methods: Patients with high-grade NHL according to t he Kiel classification were treated with the CHOEP-14 regimen, consist ing of cyclophosphamide (750 mg/m(2) i.v., day 1), doxorubicin (50 mg/ m(2), day 1), vincristine (2 mg i.v., day 1), etoposide (100 mg/m(2), days 1-3) and prednisolone (100 mg p.o., days 1-5). G-CSF, 300 mu g (u p to 75 kg body weight) or 480 mu g was applied s.c. (days 4-13). Cycl es 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 bee n treated for a total of 159 evaluable chemotherapy cycles. 24 patient s have finished 6 cycles each, and 20 patients are evaluable for respo nse. Application of the following cycle was on day 15 in 146/159 cycle s, and delay in 16 cycles (duration between 1 and 13 days) was not cau sed by neutropenia in any patient. Leucopenia <1,000/mm(3) occurred in 18/159 cycles, but never lasted longer than 4 days. White blood cell counts recovered completely by day 14 in all cycles. Toxicity was tole rable and never exceeded WHO grade 3. A complete remission (CR) was ob served in 17/20 patients, a partial remission (PR) in 2/20 patients be fore radiation therapy One patient died due to disease progression (ce rebral involvement). Conclusion: Dose intensification of the standard CHOP regimen by addition of etoposide and implementation of 14-day cyc les with growth factor support is possible without undue increase in t reatment toxicity. A randomized multicenter phase III trial has been i nitiated to test whether this significant increment in dose intensity translates into increased remission rates and/or longer remission dura tions.