Dose-escalated cyclophosphamide, doxorubicin, vincristine, prednisone, and etoposide (CHOPE) chemotherapy for patients with diffuse lymphoma

Cancer and Leukemia Group B studies 8852 and 8854

Nancy L. Bartlett, Gina R. Petroni, Barbara A. Parker, Nina Wagner-Johnston, Jon P. Gockerman, George A. Omura, George P. Canellos, M. Robertcooper, Jeffrey L. Johnson, Bruce A. Peterson

Research output: Contribution to journalArticle

Abstract

BACKGROUND. To address the feasibility and outcome of moderate dose intensification with granulocyte-colony stimulating factor (G-CSF) for patients with aggressive non-Hodgkin lymphoma (NHL), the Cancer and Leukemia Group B (CALGB) conducted two studies evaluating dose-escalated cyclophosphamide and etoposide in the cyclophosphamide, doxorubicin, vincristine, prednisone, etoposide (CHOPE) regimen. METHODS. Eligibility criteria included histologically documented, diffuse small cleaved, diffuse mixed, diffuse large cell, or immunoblastic lymphoma, Stage III-IV or bulky Stage II disease, and an ECOG performance status of 0-1. CALGB 8852, a group-wide study, accrued 227 patients: 120 patients in the pilot study to determine the maximum tolerated dose (MTD) without G-CSF and 107 in the pilot study of dose-escalated CHOPE with G-CSF. CALGB 8854, a limited-institution, Phase I study, enrolled 38 patients and determined the MTD of CHOPE with G-CSF to be used in CALGB 8852. The MTD in both studies was defined as the dose at which 50% of patients had 1) Grade 4 neutropenia or thrombocytopenia lasting 7 days or more, or 2) Grade 3-4 hemorrhage or nonhematologic toxicity (excluding alopecia, nausea, and emesis), or 3) were prevented from receiving 100% of drug on Day 22. RESULTS. The MTD of CHOPE without G-CSF was cyclophosphamide 1000 mg/m2 on Day 1 and etoposide 100 mg/m2 on Days 1-3 with doxorubicin 50 mg/m2 on Day 1, vincristine 1.4 mg/m2 (maximum, 2 mg) on Day 1, and prednisone 100 mg on Days 1-5. With the addition of G-CSF at 200 μg/m2 on Days 5-19, the MTD was cyclophosphamide 1500 mg/m2 and etoposide 160 mg/m2 on Days 1-3 with standard doses of doxorubicin, vincristine, and prednisone. Increasing the dose of G-CSF from 200 μg/m2 to 400 μg/m2 did not allow for further dose escalation. The primary toxicity in all cohorts was neutropenia. Four toxic deaths occurred on CALGB 8852. The 5-year failure free survival (FFS) and overall survival (OS) rates for eligible patients on CALGB 8852 were 31% (95% confidence interval [95%CI], 23-39) and 48% (95%CI, 40-57), respectively. The 5-year FFS and OS rates for eligible patients on CALGB 8854 were 34% (95%CI, 17-52) and 51% (95%CI, 33-70), respectively. CONCLUSIONS. Moderate dose escalation with G-CSF is feasible. However, response and survival rates of patients who receive dose-escalated CHOPE, even with the addition of G-CSF, appear similar to the rates reported with standard-dose CHOP.

Original languageEnglish (US)
Pages (from-to)207-217
Number of pages11
JournalCancer
Volume92
Issue number2
DOIs
StatePublished - Jul 15 2001
Externally publishedYes

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Vincristine
Granulocyte Colony-Stimulating Factor
Etoposide
Prednisone
Non-Hodgkin's Lymphoma
Doxorubicin
Cyclophosphamide
Leukemia
Maximum Tolerated Dose
Drug Therapy
Neoplasms
Confidence Intervals
Survival Rate
Neutropenia
Large-Cell Immunoblastic Lymphoma
Survival
Poisons
Alopecia
Thrombocytopenia
Nausea

Keywords

  • Cyclophosphamide, doxorubicin, vincristine, prednisone, and etoposide
  • Dose escalation
  • Granulocyte-colony stimulating factor
  • Non-Hodgkin lymphoma, cyclophosphamide, doxorubicin, vincristine, and prednisone

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Dose-escalated cyclophosphamide, doxorubicin, vincristine, prednisone, and etoposide (CHOPE) chemotherapy for patients with diffuse lymphoma : Cancer and Leukemia Group B studies 8852 and 8854. / Bartlett, Nancy L.; Petroni, Gina R.; Parker, Barbara A.; Wagner-Johnston, Nina; Gockerman, Jon P.; Omura, George A.; Canellos, George P.; Robertcooper, M.; Johnson, Jeffrey L.; Peterson, Bruce A.

In: Cancer, Vol. 92, No. 2, 15.07.2001, p. 207-217.

Research output: Contribution to journalArticle

Bartlett, Nancy L. ; Petroni, Gina R. ; Parker, Barbara A. ; Wagner-Johnston, Nina ; Gockerman, Jon P. ; Omura, George A. ; Canellos, George P. ; Robertcooper, M. ; Johnson, Jeffrey L. ; Peterson, Bruce A. / Dose-escalated cyclophosphamide, doxorubicin, vincristine, prednisone, and etoposide (CHOPE) chemotherapy for patients with diffuse lymphoma : Cancer and Leukemia Group B studies 8852 and 8854. In: Cancer. 2001 ; Vol. 92, No. 2. pp. 207-217.
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abstract = "BACKGROUND. To address the feasibility and outcome of moderate dose intensification with granulocyte-colony stimulating factor (G-CSF) for patients with aggressive non-Hodgkin lymphoma (NHL), the Cancer and Leukemia Group B (CALGB) conducted two studies evaluating dose-escalated cyclophosphamide and etoposide in the cyclophosphamide, doxorubicin, vincristine, prednisone, etoposide (CHOPE) regimen. METHODS. Eligibility criteria included histologically documented, diffuse small cleaved, diffuse mixed, diffuse large cell, or immunoblastic lymphoma, Stage III-IV or bulky Stage II disease, and an ECOG performance status of 0-1. CALGB 8852, a group-wide study, accrued 227 patients: 120 patients in the pilot study to determine the maximum tolerated dose (MTD) without G-CSF and 107 in the pilot study of dose-escalated CHOPE with G-CSF. CALGB 8854, a limited-institution, Phase I study, enrolled 38 patients and determined the MTD of CHOPE with G-CSF to be used in CALGB 8852. The MTD in both studies was defined as the dose at which 50{\%} of patients had 1) Grade 4 neutropenia or thrombocytopenia lasting 7 days or more, or 2) Grade 3-4 hemorrhage or nonhematologic toxicity (excluding alopecia, nausea, and emesis), or 3) were prevented from receiving 100{\%} of drug on Day 22. RESULTS. The MTD of CHOPE without G-CSF was cyclophosphamide 1000 mg/m2 on Day 1 and etoposide 100 mg/m2 on Days 1-3 with doxorubicin 50 mg/m2 on Day 1, vincristine 1.4 mg/m2 (maximum, 2 mg) on Day 1, and prednisone 100 mg on Days 1-5. With the addition of G-CSF at 200 μg/m2 on Days 5-19, the MTD was cyclophosphamide 1500 mg/m2 and etoposide 160 mg/m2 on Days 1-3 with standard doses of doxorubicin, vincristine, and prednisone. Increasing the dose of G-CSF from 200 μg/m2 to 400 μg/m2 did not allow for further dose escalation. The primary toxicity in all cohorts was neutropenia. Four toxic deaths occurred on CALGB 8852. The 5-year failure free survival (FFS) and overall survival (OS) rates for eligible patients on CALGB 8852 were 31{\%} (95{\%} confidence interval [95{\%}CI], 23-39) and 48{\%} (95{\%}CI, 40-57), respectively. The 5-year FFS and OS rates for eligible patients on CALGB 8854 were 34{\%} (95{\%}CI, 17-52) and 51{\%} (95{\%}CI, 33-70), respectively. CONCLUSIONS. Moderate dose escalation with G-CSF is feasible. However, response and survival rates of patients who receive dose-escalated CHOPE, even with the addition of G-CSF, appear similar to the rates reported with standard-dose CHOP.",
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TY - JOUR

T1 - Dose-escalated cyclophosphamide, doxorubicin, vincristine, prednisone, and etoposide (CHOPE) chemotherapy for patients with diffuse lymphoma

T2 - Cancer and Leukemia Group B studies 8852 and 8854

AU - Bartlett, Nancy L.

AU - Petroni, Gina R.

AU - Parker, Barbara A.

AU - Wagner-Johnston, Nina

AU - Gockerman, Jon P.

AU - Omura, George A.

AU - Canellos, George P.

AU - Robertcooper, M.

AU - Johnson, Jeffrey L.

AU - Peterson, Bruce A.

PY - 2001/7/15

Y1 - 2001/7/15

N2 - BACKGROUND. To address the feasibility and outcome of moderate dose intensification with granulocyte-colony stimulating factor (G-CSF) for patients with aggressive non-Hodgkin lymphoma (NHL), the Cancer and Leukemia Group B (CALGB) conducted two studies evaluating dose-escalated cyclophosphamide and etoposide in the cyclophosphamide, doxorubicin, vincristine, prednisone, etoposide (CHOPE) regimen. METHODS. Eligibility criteria included histologically documented, diffuse small cleaved, diffuse mixed, diffuse large cell, or immunoblastic lymphoma, Stage III-IV or bulky Stage II disease, and an ECOG performance status of 0-1. CALGB 8852, a group-wide study, accrued 227 patients: 120 patients in the pilot study to determine the maximum tolerated dose (MTD) without G-CSF and 107 in the pilot study of dose-escalated CHOPE with G-CSF. CALGB 8854, a limited-institution, Phase I study, enrolled 38 patients and determined the MTD of CHOPE with G-CSF to be used in CALGB 8852. The MTD in both studies was defined as the dose at which 50% of patients had 1) Grade 4 neutropenia or thrombocytopenia lasting 7 days or more, or 2) Grade 3-4 hemorrhage or nonhematologic toxicity (excluding alopecia, nausea, and emesis), or 3) were prevented from receiving 100% of drug on Day 22. RESULTS. The MTD of CHOPE without G-CSF was cyclophosphamide 1000 mg/m2 on Day 1 and etoposide 100 mg/m2 on Days 1-3 with doxorubicin 50 mg/m2 on Day 1, vincristine 1.4 mg/m2 (maximum, 2 mg) on Day 1, and prednisone 100 mg on Days 1-5. With the addition of G-CSF at 200 μg/m2 on Days 5-19, the MTD was cyclophosphamide 1500 mg/m2 and etoposide 160 mg/m2 on Days 1-3 with standard doses of doxorubicin, vincristine, and prednisone. Increasing the dose of G-CSF from 200 μg/m2 to 400 μg/m2 did not allow for further dose escalation. The primary toxicity in all cohorts was neutropenia. Four toxic deaths occurred on CALGB 8852. The 5-year failure free survival (FFS) and overall survival (OS) rates for eligible patients on CALGB 8852 were 31% (95% confidence interval [95%CI], 23-39) and 48% (95%CI, 40-57), respectively. The 5-year FFS and OS rates for eligible patients on CALGB 8854 were 34% (95%CI, 17-52) and 51% (95%CI, 33-70), respectively. CONCLUSIONS. Moderate dose escalation with G-CSF is feasible. However, response and survival rates of patients who receive dose-escalated CHOPE, even with the addition of G-CSF, appear similar to the rates reported with standard-dose CHOP.

AB - BACKGROUND. To address the feasibility and outcome of moderate dose intensification with granulocyte-colony stimulating factor (G-CSF) for patients with aggressive non-Hodgkin lymphoma (NHL), the Cancer and Leukemia Group B (CALGB) conducted two studies evaluating dose-escalated cyclophosphamide and etoposide in the cyclophosphamide, doxorubicin, vincristine, prednisone, etoposide (CHOPE) regimen. METHODS. Eligibility criteria included histologically documented, diffuse small cleaved, diffuse mixed, diffuse large cell, or immunoblastic lymphoma, Stage III-IV or bulky Stage II disease, and an ECOG performance status of 0-1. CALGB 8852, a group-wide study, accrued 227 patients: 120 patients in the pilot study to determine the maximum tolerated dose (MTD) without G-CSF and 107 in the pilot study of dose-escalated CHOPE with G-CSF. CALGB 8854, a limited-institution, Phase I study, enrolled 38 patients and determined the MTD of CHOPE with G-CSF to be used in CALGB 8852. The MTD in both studies was defined as the dose at which 50% of patients had 1) Grade 4 neutropenia or thrombocytopenia lasting 7 days or more, or 2) Grade 3-4 hemorrhage or nonhematologic toxicity (excluding alopecia, nausea, and emesis), or 3) were prevented from receiving 100% of drug on Day 22. RESULTS. The MTD of CHOPE without G-CSF was cyclophosphamide 1000 mg/m2 on Day 1 and etoposide 100 mg/m2 on Days 1-3 with doxorubicin 50 mg/m2 on Day 1, vincristine 1.4 mg/m2 (maximum, 2 mg) on Day 1, and prednisone 100 mg on Days 1-5. With the addition of G-CSF at 200 μg/m2 on Days 5-19, the MTD was cyclophosphamide 1500 mg/m2 and etoposide 160 mg/m2 on Days 1-3 with standard doses of doxorubicin, vincristine, and prednisone. Increasing the dose of G-CSF from 200 μg/m2 to 400 μg/m2 did not allow for further dose escalation. The primary toxicity in all cohorts was neutropenia. Four toxic deaths occurred on CALGB 8852. The 5-year failure free survival (FFS) and overall survival (OS) rates for eligible patients on CALGB 8852 were 31% (95% confidence interval [95%CI], 23-39) and 48% (95%CI, 40-57), respectively. The 5-year FFS and OS rates for eligible patients on CALGB 8854 were 34% (95%CI, 17-52) and 51% (95%CI, 33-70), respectively. CONCLUSIONS. Moderate dose escalation with G-CSF is feasible. However, response and survival rates of patients who receive dose-escalated CHOPE, even with the addition of G-CSF, appear similar to the rates reported with standard-dose CHOP.

KW - Cyclophosphamide, doxorubicin, vincristine, prednisone, and etoposide

KW - Dose escalation

KW - Granulocyte-colony stimulating factor

KW - Non-Hodgkin lymphoma, cyclophosphamide, doxorubicin, vincristine, and prednisone

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