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, N. Akatsuka, A. Ishida, N. Michikawa, Y. Masuda, H. Uchida, Mitsuru Murata, M. Kizaki, Y. Ikeda

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 μg/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 cyclophosphamide 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/μl 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

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Vincristine
Granulocyte Colony-Stimulating Factor
Prednisolone
Non-Hodgkin's Lymphoma
Doxorubicin
Cyclophosphamide
Mucositis
Transaminases
Neutropenia
Platelet Count
Leukocyte Count
Hepatitis B virus
Hepatitis
Hemoglobins
Therapeutics
Safety

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

  • Cancer Research
  • Oncology

Cite this

Dose escalation of biweekly cyclophosphamide, doxorubicin, vincristine, and prednisolone using recombinant human granulocyte colony stimulating factor in non-Hodgkin's lymphoma. / Tanosaki, Ryuji; Okamoto, Shinichiro; Akatsuka, N.; Ishida, A.; Michikawa, N.; Masuda, Y.; Uchida, H.; Murata, Mitsuru; Kizaki, M.; Ikeda, Y.

In: Cancer, Vol. 74, No. 7, 1994, p. 1939-1944.

Research output: Contribution to journalArticle

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title = "Dose escalation of biweekly cyclophosphamide, doxorubicin, vincristine, and prednisolone using recombinant human granulocyte colony stimulating factor in non-Hodgkin's lymphoma",
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 μg/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 cyclophosphamide 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/μl 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.",
keywords = "CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) therapy, dose intensity, non-Hodgkin's lymphoma, recombinant human granulocyte colony stimulating factor (rhG-CSF)",
author = "Ryuji Tanosaki and Shinichiro Okamoto and N. Akatsuka and A. Ishida and N. Michikawa and Y. Masuda and H. Uchida and Mitsuru Murata and M. Kizaki and Y. Ikeda",
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T1 - Dose escalation of biweekly cyclophosphamide, doxorubicin, vincristine, and prednisolone using recombinant human granulocyte colony stimulating factor in non-Hodgkin's lymphoma

AU - Tanosaki, Ryuji

AU - Okamoto, Shinichiro

AU - Akatsuka, N.

AU - Ishida, A.

AU - Michikawa, N.

AU - Masuda, Y.

AU - Uchida, H.

AU - Murata, Mitsuru

AU - Kizaki, M.

AU - Ikeda, Y.

PY - 1994

Y1 - 1994

N2 - 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 μg/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 cyclophosphamide 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/μl 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.

AB - 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 μg/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 cyclophosphamide 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/μl 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.

KW - CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) therapy

KW - dose intensity

KW - non-Hodgkin's lymphoma

KW - recombinant human granulocyte colony stimulating factor (rhG-CSF)

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