Randomized phase II study of biweekly CHOP and dose-escalated CHOP with prophylactic use of lenograstim (glycosylated G-CSF) in aggressive non-Hodgkin's lymphoma: Japan Clinical Oncology Group Study 9505

Background: CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) is accepted as the best available standard treatment for first-line chemotherapy in aggressive non-Hodgkin's lymphoma (NHL). However, the therapeutic efficacy of CHOP remains unsatisfactory, particularly in high-intermediate risk and high risk patients, and a new strategy is warranted in this patient population. The aim of the present study was to explore a suitable therapeutic-intensified regimen for the treatment of aggressive NHL. Patients and methods: Between May 1995 and July 1998, a total of 70 patients with high-intermediate risk or high risk aggressive NHL, according to the International Prognostic Index, were enrolled and randomly assigned to receive either eight cycles of standard CHOP (cyclophosphamide 750 mg/m(2), doxorubicin 50 mg/m(2), vincristine 1.4 mg/m(2) and prednisolone 100 mg for 5 days) every 2 weeks, or six cycles of dose-escalated CHOP (cyclophosphamide 1,500 mg/m(2), doxorubicm 70 mg/m(2), vincristine 1.4 mg/m(2) and prednisolone 100 mg for 5 days) every 3 weeks. Lenograstim (glycosylated rHuG-CSF), at a dose of 2 mug/kg/day s.c., was administered daily from day 3 until day 13 with biweekly CHOP and until day 20 with the dose-escalated CHOP. The primary endpoint was complete response rate. Results: The complete response rate was 60% [21 of 35; 95% confidence interval (CI) 42% to 76%] with biweekly CHOP and 51% (18 of 35; 95% CI 34% to 69%) with dose-escalated CHOP. The major toxicity was grade 4 neutropenia and was more frequent in the dose-escalated CHOP arm (86%) than in the biweekly CHOP arm (50%). Grade 4 thrombocytopenia was also more frequent in the dose-escalated CHOP arm (20%) than the biweekly CHOP arm (3%). Non-hematological toxicities were acceptable in both arms. One treatment-related death (due to cardiac arrhythmia) was observed in a dose-escalated CHOP patient. Progression-free survival at 3 years was 43% (95% CI 27% to 59%) in the biweekly CHOP arm and 31% (95% CI 16% to 47%) in the dose-escalated CHOP arm Although seven patients were deemed ineligible by central review of the pathological diagnosis, the results for both eligible and all enrolled patients were similar. Conclusions: Similar complete response rates and progression-free survival rates, but lower toxicity, indicated that biweekly CHOP was superior to dose-escalated CHOP in the treatment of aggressive NHL. Based on these results, the Lymphoma Study Group of the Japan Clinical Oncology Group is conducting a randomized phase III study comparing biweekly CHOP with standard CHOP in newly diagnosed patients with advanced-stage aggressive NHL.