Dose escalation of biweekly cyclophosphamide, doxorubicin, vincristine, and prednisolone using recombinant human granulocyte colony stimulating factor in non‐Hodgkin's lymphoma

Ryuji Tanosaki, Shinichiro Okamoto, Noriko Akatsuka, Akaru Ishida, Naohiko Michikawa, Yoshiniro Masuda, Hideo Uchida, Mitsuru Murata, Masahiro Kizako, Yasuo Lkeda

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1939-1944
Number of pages6
JournalCancer
Volume74
Issue number7
DOIs
Publication statusPublished - 1994 Oct 1

Keywords

  • CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) therapy
  • dose intensity
  • non‐Hodgkin's lymphoma
  • recombinant human granulocyte colony stimulating factor (rhG‐CSF)

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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