RANDOMIZED COMPARISON OF CHOEP VERSUS ALTERNATING HCHOP IVEP FOR HIGH-GRADE NON-HODGKINS-LYMPHOMAS - TREATMENT RESULTS AND PROGNOSTIC FACTOR-ANALYSIS IN A MULTICENTER TRIAL/

Background: With CHOP, the standard protocol of recent decades, about 30% of long-term survival has been reported. A number of studies using more aggressive multidrug regimens or alternating chemotherapies have recently suggested higher CR rates and increased survival. In 1989 we reported similar results with a combined-modality treatment administe ring 6 cycles of CHOP supplemented with etoposide and an involved fiel d irradiation for patients in PR or CR. Patients and methods: To confi rm the efficacy of this approach, we initiated a prospective randomise d trial comparing 4 cycles of CHOP-VP16 (CHOEP) with 4 cycles of two a lternating regimens,'hCHOP and IVEP'. One hundred seventy-five patient s with high-grade non-Hodgkin's lymphomas stages II-IV were stratified for age, stage and LDH and randomised to receive either four cycles o f cyclophosphamide, doxorubicin, vincristine, etoposide, prednisolone (CHOEP) in arm A or four cycles of chemotherapy with a dose-intensifie d CHOP (hCHOP) alternating with ifosfamide, etoposide, vindesine, pred nisolone (IVEP) in arm B. After four cycles of chemotherapy an involve d field irradiation with a total dose of 35 Gy was given to all patien ts demonstrated to be in complete or partial remission. Results: Of th e 185 randomised patients, 175 were eligible and 171 evaluable for res ponse and survival. One hundred forty-six of the 171 patients (85%) ac hieved complete remission (CR) with 87% and 84% CRs in arms A and B, r espectively. With a median follow-up of 36 months the estimated overal l survival at 2 years is 66% and 73% for arms A and B, respectively Th e percentage of ah patients in first CR is estimated to be 59% and 55% at 2 years for arms A and B, respectively. None of the differences in CR rate, survival, or relapse-free survival are statistically signifi cant. Multivariate analysis of subgroups incorporating the factors of sex, age, performance status, stage, B symptoms, bulky disease, LDH an d histology revealed that only stage and LDH were factors which indepe ndently affected outcome. The estimated 2-year survival rate of patien ts with stages II, III and IV is predicted to be 84%, 62% and 52%, res pectively. Patients with LDH >250 U/l have an estimated survival of 52 % at 2 years versus 84% for patients with LDH less than or equal to 25 0 U/l. According to the newly proposed international score system, the 2-year survival was 81% for low-risk-, 64% for low intermediate risk- , 50% for high intermediate risk-, and 43% for high-risk patients. The toxicity in both arms was tolerable. Three patients died of treatment -related causes (2 in arm A, 1 in arm B). The main toxicity was haemat ological with 75% of patients suffering from grades 3 or 4 neutropenia at some point during treatment. Conclusions: We observed no superior benefit for alternating regimens, and conclude that both are effective treatment protocols for aggressive histologic-type malignant lymphoma s. The results obtained with four cycles of polychemotherapy followed by an involved field irradiation are comparable to programs using more aggressive and/or prolonged chemotherapy.