Background. Several uncontrolled trials have suggested that dose intensity of chemotherapy is a crucial determinant of treatment outcome for patients with non‐Hodgkin's lymphoma (NHL). To explore the possibility of increasing dose intensity, a dose‐escalation study of cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) using recombinant human granulocyte colony stimulating factor (rhG‐CSF) was initiated. Methods. First, the feasibility of standard dose CHOP (750 mg/m2 cyclophosphamide intravenously [i. v.] on Day 1; 50 mg/m2 doxorubicin i. v. on Day 1; 1.4 mg/m2 vincristine i. v. on Day 1; and 100 mg/body prednisolone orally on Days 1–5) repeated biweekly at the original dose was assessed. rhG‐CSF was given subcutaneously at doses of 2–5 rg/kg every day or every other day on Days 3–13. The safety of increasing the dose of cyclophosphamide during biweekly CHOP then was tested. Besides the standard dose (750 mg/m2), two dose levels of cyclphosphamide were set (1200 mg/m2 and 1500 mg/m2 in patients younger than 61 years of age, and 1200 mg/m2 in patients 61–75 years old). Results. Twenty‐seven patients with NHL who had received minimal or no previous treatment were enrolled in this study. In the 750 mg/m2 group, 9 patients received 3–6 cycles of treatment (mean, 3.9 cycles), in the 1200 mg/m2 group, 10 patients received 3–6 cycles (mean, 4.8), and in the 1500 mg/m2 group, all 8 patients received 6 cycles. No significant differences among the groups were observed in the extent and the duration of neutropenia in each cycle, and a leukocyte count of more than 3000/μ1 on Day 15 was achieved in all 131 cycles. Hemoglobin values and platelet counts, however, decreased in the later cycles in the 1500 mg/m2 group. Two patients were hepatitis‐B virus carriers, one of whom died of fulminant hepatitis after completion of six cycles. Another patient developed a transient increase of transaminases after the second cycle. One other patient developed Grade 4 mucositis (World Health Organization scale). The numbers of patients who achieved complete and partial responses, respectively, were 4 (50%) and 2 (25%) in the 750 mg/m2 group, 8 (80%) and 2 (20%) in the 1200 mg/m2 group, and 8 (100%) and 0 (0%) in the 1500 mg/m2 group. Conclusions. The dose of cyclophosphamide in biweekly CHOP can be increased up to 1500 mg/m2 with no increase in the incidence of treatment‐related early mortalities without any organ damage in younger patients. The efficacy of this dose intensification of CHOP currently is being investigated in a multicenter prospective randomized trial using three different dose levels of cyclophosphamide.
|出版ステータス||Published - 1994 10月 1|
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