Annals of Oncology 13:1347-1355, 2002
© 2002 European Society for Medical Oncology
Original Paper |
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
1 Division of Hematology and Oncology, National Cancer Center Hospital East, Kashiwa; 2 JCOG Data Center, Cancer Information and Epidemiology Division, National Cancer Center Research Institute, Tokyo; 3 Department of Hematology and Chemotherapy, Aichi Cancer Center, Nagoya; 4 Department of Medical Oncology, Niigata Cancer Center Hospital, Niigata; 5 Department of Hematology, Sapporo National Hospital, Sapporo; 6 Department of Hematology, National Kyusyu Cancer Center, Fukuoka; 7 Department of Internal Medicine, Daisan Hospital, The Jikei University School of Medicine, Tokyo; 8 Division of Hematology and Immunology, Department of Internal Medicine, Ohtsu Red Cross Hospital, Ohtsu; 9 Department of Hematology, Sasebo City General Hospital, Sasebo, 10 Department of Internal Medicine, Iwaki Kyoritsu General Hospital, Iwaki; 11 Third Department of Internal Medicine, Kyoto Prefectural University School of Medicine, Kyoto; 12 Institute for Clinical Research, Kumamoto National Hospital, Kumamoto; 13 Department of Internal Medicine, Tokai University, Isehara; 14 Nagoya National Hospital, Nagoya; 15 Hematology Division, National Cancer Center Hospital, Tokyo, Japan
Received 10 December 2001; revised 20 March 2002; accepted 22 May 2002
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/m2, doxorubicin 50 mg/m2, vincristine 1.4 mg/m2 and prednisolone 100 mg for 5 days) every 2 weeks, or six cycles of dose-escalated CHOP (cyclophosphamide 1,500 mg/m2, doxorubicin 70 mg/m2, vincristine 1.4 mg/m2 and prednisolone 100 mg for 5 days) every 3 weeks. Lenograstim (glycosylated rHuG-CSF), at a dose of 2 µg/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.
Key words: biweekly CHOP, dose-escalated CHOP, dose intensity, G-CSF, non-Hodgkin’s lymphoma
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