PROMECE-CYTABOM VS MACOP-B IN ADVANCED AGGRESSIVE NON-HODGKINS-LYMPHOMA - LONG-TERM RESULTS OF A MULTICENTER STUDY OF THE ITALIAN LYMPHOMA STUDY-GROUP (GISL)

A randomized trial was designed in order to compare the efficacy and feasibility of ProMECE-CytaBOM (P-C) and MACOP-B (M-B) in patients with advanced, aggressive non Hodgkin's lymphoma (NHL). P-C and M-B were chosen due to their association with a very high complete remission rate when compared to other published protocols. The study was conducted on 210 patients with intermediate or high-grade NHL in stage I bulky, or stages II-IV, randomized to receive either 6 courses of P-C delivered every 28 days (106 patients), or 12 weeks of M-B chemotherapy (104 patients). In both regimens doxorubicin was replaced by a 20% higher dose of epidoxorubicin (i.e. 30 mg/m(2) of the analog). At the end of induction therapy patients could receive additional radiotherapy to residual masses or to sites of previous bulky disease. The two groups of patients were compared for response rates, number and severity of therapy related side effects, overall survival, disease-free survival, and time to treatment failure. Sixty-five patients (62%) treated with P-C and 69 patients (67%) treated with M-B achieved a complete remission, with no significant differences between the two treatment arms (P = 0.13). The overall objective response rate (complete + partial remission) was 74% for patients treated with P-C, and 81% for patients treated with M-B, respectively. The 4-year relapse-free survival rate was 59% for P-C and 69% for M-B, respectively (P = 0.11). We observed an eventual total of 120 treatment failures, 64 (61%) in the group treated with P-C and 56 (54%) among those treated with M-B (P = 0.29). Patients alive without disease at four yeats were estimated to be 42% in the P-C arm and 49% in the M-B arm (P = 0.27). The estimated 4-year overall survival was 54% for P-C and 61% for M-B, and the differences were also not significant (P = 0.29). Patients treated with M-B experienced more and more severe side effects, including mucositis, infections, neurologic, pulmonary and cardiac abnormalities. Patients treated with P-C had a 1.3 g mean decrease of hemoglobin over the induction therapy, while patients treated with M-B experienced a 2.2 g mean decrease (P = 0.01). In conclusion, both P-C and M-B resulted in effective treatment for patients with aggressive NHL, and provided similar activity. However P-C was more manageable in an outpatient setting and produced less acute toxic effects.