The addition of interferon or high dose cyclophosphamide to standard chemotherapy in the treatment of patients with multiple myeloma: Phase III Eastern Cooperative Oncology Group Clinical Trial EST 9486

Martin M. Oken, Traci Leong, Raymond Lenhard, Philip R. Greipp, Neil E. Kay, Brian Van Ness, Rudolph M. Keimowitz, Robert A. Kyle

Research output: Contribution to journalArticle

Abstract

BACKGROUND. Interferon (IFN) has demonstrated activity in the treatment of patients with multiple myeloma. A previous Eastern Cooperative Oncology Group (ECOG) study suggested that the rates of complete response (CR) and survival were increased with a regimen that alternated IFN with chemotherapy. The current study was designed to evaluate the effect of adding alternating cycles of IFN or early intensification with high dose cyclophosphamide (HiCy) to the VBMCP regimen for the treatment of multiple myeloma patients. METHODS. From February 1988 to May 1992, the ECOG entered previously untreated patients with active multiple myeloma on a study in which they were randomized to VBMCP (vincristine 1.2 mg/m2 administered intravenously [i.v.] on Day 1, BCNU 20 mg/m2 i.v. on Day 1, melphalan 8 mg/m2 administered orally [p.o.] on Days 1-4, cyclophosphamide 400 mg/m2 i.v. on Day 1, and prednisone 40 mg/m2 p.o. on Days 1-7; 5-week cycles) or VBMCP + rIFN(α2), the latter given at 5 Mu/m2 3 times a week starting on Day 22 of each 6-week cycle after 2 initial cycles of VBMCP. Patients younger than 70 years were also randomized to a third treatment that substituted cyclophosphamide 600 mg/m2 i.v. on Days 1-4 and prednisone 100 mg/m2 p.o. on Days 1-4 for cycles 3 and 5 of VBMCP (VBMCP + HiCy). Treatment was continued for 2 years. RESULTS. Of the 653 patients entered, 628 were eligible for the study. All were evaluated for response. With median follow-up for surviving patients of 54 months, the median survival duration was 42 months-1 year longer than usually reported for melphalan combined with prednisone. A comparison of the three regimens revealed no significant difference in the rates of survival or objective response (OR). However, CRs were increased among patients treated with VBMCP + rIFN(α2) compared with VBMCP alone (18% vs. 10%, P = 0.03). Patients treated with VBMCP + rIFN(α2) had a longer response duration than patients treated with VBMCP alone (30 vs. 25 months, P = 0.035). There was a greater response rate with the IFN regimen among elderly patients (OR and CR = 67% and 31%, respectively) and Patients with immunoglobulin A (IgA) myeloma (OR and CR = 83% and 29%, respectively). Severe infections were seen as often with VBMCP as with VBMCP + rIFN(α2) (13% vs. 15%), but they were more frequent with VBMCP + HiCy (25%). CONCLUSIONS. VBMCP + rIFN(α2) yields a higher rate of CR and a longer response duration than VBMCP alone but appears to make no difference in the rates of overall response or survival compared with VBMCP or VBMCP + HiCy. The superior ability of VBMCP + rIFN(α2) induction therapy to produce CR and more durable responses, as well as its activity in older patients and in those with IgA myeloma, suggest that this therapy has important biologic activity in myeloma and merits further clinical investigation.

Original languageEnglish (US)
Pages (from-to)957-968
Number of pages12
JournalCancer
Volume86
Issue number6
DOIs
StatePublished - Sep 15 1999

Fingerprint

Multiple Myeloma
Cyclophosphamide
Interferons
Clinical Trials
Drug Therapy
Therapeutics
Prednisone
Melphalan
Immunoglobulin A
Survival
Carmustine
Vincristine
Survival Rate

Keywords

  • Complete remission
  • Interferon
  • Multiple myeloma
  • Randomized clinical trial
  • Survival

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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The addition of interferon or high dose cyclophosphamide to standard chemotherapy in the treatment of patients with multiple myeloma : Phase III Eastern Cooperative Oncology Group Clinical Trial EST 9486. / Oken, Martin M.; Leong, Traci; Lenhard, Raymond; Greipp, Philip R.; Kay, Neil E.; Van Ness, Brian; Keimowitz, Rudolph M.; Kyle, Robert A.

In: Cancer, Vol. 86, No. 6, 15.09.1999, p. 957-968.

Research output: Contribution to journalArticle

Oken, Martin M. ; Leong, Traci ; Lenhard, Raymond ; Greipp, Philip R. ; Kay, Neil E. ; Van Ness, Brian ; Keimowitz, Rudolph M. ; Kyle, Robert A. / The addition of interferon or high dose cyclophosphamide to standard chemotherapy in the treatment of patients with multiple myeloma : Phase III Eastern Cooperative Oncology Group Clinical Trial EST 9486. In: Cancer. 1999 ; Vol. 86, No. 6. pp. 957-968.
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abstract = "BACKGROUND. Interferon (IFN) has demonstrated activity in the treatment of patients with multiple myeloma. A previous Eastern Cooperative Oncology Group (ECOG) study suggested that the rates of complete response (CR) and survival were increased with a regimen that alternated IFN with chemotherapy. The current study was designed to evaluate the effect of adding alternating cycles of IFN or early intensification with high dose cyclophosphamide (HiCy) to the VBMCP regimen for the treatment of multiple myeloma patients. METHODS. From February 1988 to May 1992, the ECOG entered previously untreated patients with active multiple myeloma on a study in which they were randomized to VBMCP (vincristine 1.2 mg/m2 administered intravenously [i.v.] on Day 1, BCNU 20 mg/m2 i.v. on Day 1, melphalan 8 mg/m2 administered orally [p.o.] on Days 1-4, cyclophosphamide 400 mg/m2 i.v. on Day 1, and prednisone 40 mg/m2 p.o. on Days 1-7; 5-week cycles) or VBMCP + rIFN(α2), the latter given at 5 Mu/m2 3 times a week starting on Day 22 of each 6-week cycle after 2 initial cycles of VBMCP. Patients younger than 70 years were also randomized to a third treatment that substituted cyclophosphamide 600 mg/m2 i.v. on Days 1-4 and prednisone 100 mg/m2 p.o. on Days 1-4 for cycles 3 and 5 of VBMCP (VBMCP + HiCy). Treatment was continued for 2 years. RESULTS. Of the 653 patients entered, 628 were eligible for the study. All were evaluated for response. With median follow-up for surviving patients of 54 months, the median survival duration was 42 months-1 year longer than usually reported for melphalan combined with prednisone. A comparison of the three regimens revealed no significant difference in the rates of survival or objective response (OR). However, CRs were increased among patients treated with VBMCP + rIFN(α2) compared with VBMCP alone (18{\%} vs. 10{\%}, P = 0.03). Patients treated with VBMCP + rIFN(α2) had a longer response duration than patients treated with VBMCP alone (30 vs. 25 months, P = 0.035). There was a greater response rate with the IFN regimen among elderly patients (OR and CR = 67{\%} and 31{\%}, respectively) and Patients with immunoglobulin A (IgA) myeloma (OR and CR = 83{\%} and 29{\%}, respectively). Severe infections were seen as often with VBMCP as with VBMCP + rIFN(α2) (13{\%} vs. 15{\%}), but they were more frequent with VBMCP + HiCy (25{\%}). CONCLUSIONS. VBMCP + rIFN(α2) yields a higher rate of CR and a longer response duration than VBMCP alone but appears to make no difference in the rates of overall response or survival compared with VBMCP or VBMCP + HiCy. The superior ability of VBMCP + rIFN(α2) induction therapy to produce CR and more durable responses, as well as its activity in older patients and in those with IgA myeloma, suggest that this therapy has important biologic activity in myeloma and merits further clinical investigation.",
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TY - JOUR

T1 - The addition of interferon or high dose cyclophosphamide to standard chemotherapy in the treatment of patients with multiple myeloma

T2 - Phase III Eastern Cooperative Oncology Group Clinical Trial EST 9486

AU - Oken, Martin M.

AU - Leong, Traci

AU - Lenhard, Raymond

AU - Greipp, Philip R.

AU - Kay, Neil E.

AU - Van Ness, Brian

AU - Keimowitz, Rudolph M.

AU - Kyle, Robert A.

PY - 1999/9/15

Y1 - 1999/9/15

N2 - BACKGROUND. Interferon (IFN) has demonstrated activity in the treatment of patients with multiple myeloma. A previous Eastern Cooperative Oncology Group (ECOG) study suggested that the rates of complete response (CR) and survival were increased with a regimen that alternated IFN with chemotherapy. The current study was designed to evaluate the effect of adding alternating cycles of IFN or early intensification with high dose cyclophosphamide (HiCy) to the VBMCP regimen for the treatment of multiple myeloma patients. METHODS. From February 1988 to May 1992, the ECOG entered previously untreated patients with active multiple myeloma on a study in which they were randomized to VBMCP (vincristine 1.2 mg/m2 administered intravenously [i.v.] on Day 1, BCNU 20 mg/m2 i.v. on Day 1, melphalan 8 mg/m2 administered orally [p.o.] on Days 1-4, cyclophosphamide 400 mg/m2 i.v. on Day 1, and prednisone 40 mg/m2 p.o. on Days 1-7; 5-week cycles) or VBMCP + rIFN(α2), the latter given at 5 Mu/m2 3 times a week starting on Day 22 of each 6-week cycle after 2 initial cycles of VBMCP. Patients younger than 70 years were also randomized to a third treatment that substituted cyclophosphamide 600 mg/m2 i.v. on Days 1-4 and prednisone 100 mg/m2 p.o. on Days 1-4 for cycles 3 and 5 of VBMCP (VBMCP + HiCy). Treatment was continued for 2 years. RESULTS. Of the 653 patients entered, 628 were eligible for the study. All were evaluated for response. With median follow-up for surviving patients of 54 months, the median survival duration was 42 months-1 year longer than usually reported for melphalan combined with prednisone. A comparison of the three regimens revealed no significant difference in the rates of survival or objective response (OR). However, CRs were increased among patients treated with VBMCP + rIFN(α2) compared with VBMCP alone (18% vs. 10%, P = 0.03). Patients treated with VBMCP + rIFN(α2) had a longer response duration than patients treated with VBMCP alone (30 vs. 25 months, P = 0.035). There was a greater response rate with the IFN regimen among elderly patients (OR and CR = 67% and 31%, respectively) and Patients with immunoglobulin A (IgA) myeloma (OR and CR = 83% and 29%, respectively). Severe infections were seen as often with VBMCP as with VBMCP + rIFN(α2) (13% vs. 15%), but they were more frequent with VBMCP + HiCy (25%). CONCLUSIONS. VBMCP + rIFN(α2) yields a higher rate of CR and a longer response duration than VBMCP alone but appears to make no difference in the rates of overall response or survival compared with VBMCP or VBMCP + HiCy. The superior ability of VBMCP + rIFN(α2) induction therapy to produce CR and more durable responses, as well as its activity in older patients and in those with IgA myeloma, suggest that this therapy has important biologic activity in myeloma and merits further clinical investigation.

AB - BACKGROUND. Interferon (IFN) has demonstrated activity in the treatment of patients with multiple myeloma. A previous Eastern Cooperative Oncology Group (ECOG) study suggested that the rates of complete response (CR) and survival were increased with a regimen that alternated IFN with chemotherapy. The current study was designed to evaluate the effect of adding alternating cycles of IFN or early intensification with high dose cyclophosphamide (HiCy) to the VBMCP regimen for the treatment of multiple myeloma patients. METHODS. From February 1988 to May 1992, the ECOG entered previously untreated patients with active multiple myeloma on a study in which they were randomized to VBMCP (vincristine 1.2 mg/m2 administered intravenously [i.v.] on Day 1, BCNU 20 mg/m2 i.v. on Day 1, melphalan 8 mg/m2 administered orally [p.o.] on Days 1-4, cyclophosphamide 400 mg/m2 i.v. on Day 1, and prednisone 40 mg/m2 p.o. on Days 1-7; 5-week cycles) or VBMCP + rIFN(α2), the latter given at 5 Mu/m2 3 times a week starting on Day 22 of each 6-week cycle after 2 initial cycles of VBMCP. Patients younger than 70 years were also randomized to a third treatment that substituted cyclophosphamide 600 mg/m2 i.v. on Days 1-4 and prednisone 100 mg/m2 p.o. on Days 1-4 for cycles 3 and 5 of VBMCP (VBMCP + HiCy). Treatment was continued for 2 years. RESULTS. Of the 653 patients entered, 628 were eligible for the study. All were evaluated for response. With median follow-up for surviving patients of 54 months, the median survival duration was 42 months-1 year longer than usually reported for melphalan combined with prednisone. A comparison of the three regimens revealed no significant difference in the rates of survival or objective response (OR). However, CRs were increased among patients treated with VBMCP + rIFN(α2) compared with VBMCP alone (18% vs. 10%, P = 0.03). Patients treated with VBMCP + rIFN(α2) had a longer response duration than patients treated with VBMCP alone (30 vs. 25 months, P = 0.035). There was a greater response rate with the IFN regimen among elderly patients (OR and CR = 67% and 31%, respectively) and Patients with immunoglobulin A (IgA) myeloma (OR and CR = 83% and 29%, respectively). Severe infections were seen as often with VBMCP as with VBMCP + rIFN(α2) (13% vs. 15%), but they were more frequent with VBMCP + HiCy (25%). CONCLUSIONS. VBMCP + rIFN(α2) yields a higher rate of CR and a longer response duration than VBMCP alone but appears to make no difference in the rates of overall response or survival compared with VBMCP or VBMCP + HiCy. The superior ability of VBMCP + rIFN(α2) induction therapy to produce CR and more durable responses, as well as its activity in older patients and in those with IgA myeloma, suggest that this therapy has important biologic activity in myeloma and merits further clinical investigation.

KW - Complete remission

KW - Interferon

KW - Multiple myeloma

KW - Randomized clinical trial

KW - Survival

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