Phase I trial of dose escalation with growth factor support in patients with previously untreated diffuse aggressive lymphomas: Determination of the maximum-tolerated dose of ProMACE-CytaBOM

L. I. Gordon, J. Anderson, Thomas Matthew Habermann, J. N. Winter, J. Glick, R. J. Schilder, P. Cassileth

Research output: Contribution to journalArticle

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Abstract

Purpose: The aim of this study was to determine the maximum-tolerated dose (MTD) of cyclophosphamide, doxorubicin, etoposide, prednisone, bleomycin, cytarabine, methotrexate, and leucovorin (ProMACE-CytaBOM) when the myelotoxic drugs cyclophosphamide, doxorubicin, etoposide, and cytarabine are escalated. Patients and Methods: Thirty-eight eligible patients with diffuse aggressive non-Hodgkin's lymphoma were treated on a phase I trial of dose escalation using the ProMACE-CytaBOM regimen and granulocyte-macrophage colony-stimulating factor (GM-CSF; Schering, Kenilworth, NJ). Patients were treated with recombinant (r)GM-CSF 10 μg/kg/d subcutaneously from day 9 to 19. Twenty-seven patients had stage IV disease, four had stage III, and seven had bulky stage II. Half of the patients had bone marrow involvement. The median age was 45 years. Results: We found that the MTD was 200% for the escalated drugs in this regimen (although we never escalated above the MTD or defined by dose-limiting toxicity) and that the normalized dose-intensity (NDI; defined as the ratio of the received dose-intensity to the 100% dose- intensity of ProMACE-CytaBOM) decreased with each cycle and was lower for the day-8 drug (cytarabine) than for the day- 1 drugs. The complete response (CR) rate was 66%, and 92% of patients who achieved CR are alive without disease with a median follow-up time for survival of 3.6 years. Conclusion: The MTD of cyclophosphamide, doxorubicin, etoposide, and cytarabine in the ProMACE- CytaBOM regimen given with growth factor support is 200%, and this dose should be tested in larger phase II trials.

Original languageEnglish (US)
Pages (from-to)1275-1281
Number of pages7
JournalJournal of Clinical Oncology
Volume14
Issue number4
StatePublished - Apr 1996
Externally publishedYes

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Maximum Tolerated Dose
Non-Hodgkin's Lymphoma
Intercellular Signaling Peptides and Proteins
Cytarabine
Etoposide
Granulocyte-Macrophage Colony-Stimulating Factor
Doxorubicin
Cyclophosphamide
Pharmaceutical Preparations
Leucovorin
Bleomycin
Prednisone
Methotrexate
Bone Marrow
Survival

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Phase I trial of dose escalation with growth factor support in patients with previously untreated diffuse aggressive lymphomas : Determination of the maximum-tolerated dose of ProMACE-CytaBOM. / Gordon, L. I.; Anderson, J.; Habermann, Thomas Matthew; Winter, J. N.; Glick, J.; Schilder, R. J.; Cassileth, P.

In: Journal of Clinical Oncology, Vol. 14, No. 4, 04.1996, p. 1275-1281.

Research output: Contribution to journalArticle

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title = "Phase I trial of dose escalation with growth factor support in patients with previously untreated diffuse aggressive lymphomas: Determination of the maximum-tolerated dose of ProMACE-CytaBOM",
abstract = "Purpose: The aim of this study was to determine the maximum-tolerated dose (MTD) of cyclophosphamide, doxorubicin, etoposide, prednisone, bleomycin, cytarabine, methotrexate, and leucovorin (ProMACE-CytaBOM) when the myelotoxic drugs cyclophosphamide, doxorubicin, etoposide, and cytarabine are escalated. Patients and Methods: Thirty-eight eligible patients with diffuse aggressive non-Hodgkin's lymphoma were treated on a phase I trial of dose escalation using the ProMACE-CytaBOM regimen and granulocyte-macrophage colony-stimulating factor (GM-CSF; Schering, Kenilworth, NJ). Patients were treated with recombinant (r)GM-CSF 10 μg/kg/d subcutaneously from day 9 to 19. Twenty-seven patients had stage IV disease, four had stage III, and seven had bulky stage II. Half of the patients had bone marrow involvement. The median age was 45 years. Results: We found that the MTD was 200{\%} for the escalated drugs in this regimen (although we never escalated above the MTD or defined by dose-limiting toxicity) and that the normalized dose-intensity (NDI; defined as the ratio of the received dose-intensity to the 100{\%} dose- intensity of ProMACE-CytaBOM) decreased with each cycle and was lower for the day-8 drug (cytarabine) than for the day- 1 drugs. The complete response (CR) rate was 66{\%}, and 92{\%} of patients who achieved CR are alive without disease with a median follow-up time for survival of 3.6 years. Conclusion: The MTD of cyclophosphamide, doxorubicin, etoposide, and cytarabine in the ProMACE- CytaBOM regimen given with growth factor support is 200{\%}, and this dose should be tested in larger phase II trials.",
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T1 - Phase I trial of dose escalation with growth factor support in patients with previously untreated diffuse aggressive lymphomas

T2 - Determination of the maximum-tolerated dose of ProMACE-CytaBOM

AU - Gordon, L. I.

AU - Anderson, J.

AU - Habermann, Thomas Matthew

AU - Winter, J. N.

AU - Glick, J.

AU - Schilder, R. J.

AU - Cassileth, P.

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N2 - Purpose: The aim of this study was to determine the maximum-tolerated dose (MTD) of cyclophosphamide, doxorubicin, etoposide, prednisone, bleomycin, cytarabine, methotrexate, and leucovorin (ProMACE-CytaBOM) when the myelotoxic drugs cyclophosphamide, doxorubicin, etoposide, and cytarabine are escalated. Patients and Methods: Thirty-eight eligible patients with diffuse aggressive non-Hodgkin's lymphoma were treated on a phase I trial of dose escalation using the ProMACE-CytaBOM regimen and granulocyte-macrophage colony-stimulating factor (GM-CSF; Schering, Kenilworth, NJ). Patients were treated with recombinant (r)GM-CSF 10 μg/kg/d subcutaneously from day 9 to 19. Twenty-seven patients had stage IV disease, four had stage III, and seven had bulky stage II. Half of the patients had bone marrow involvement. The median age was 45 years. Results: We found that the MTD was 200% for the escalated drugs in this regimen (although we never escalated above the MTD or defined by dose-limiting toxicity) and that the normalized dose-intensity (NDI; defined as the ratio of the received dose-intensity to the 100% dose- intensity of ProMACE-CytaBOM) decreased with each cycle and was lower for the day-8 drug (cytarabine) than for the day- 1 drugs. The complete response (CR) rate was 66%, and 92% of patients who achieved CR are alive without disease with a median follow-up time for survival of 3.6 years. Conclusion: The MTD of cyclophosphamide, doxorubicin, etoposide, and cytarabine in the ProMACE- CytaBOM regimen given with growth factor support is 200%, and this dose should be tested in larger phase II trials.

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