Ifosfamide and etoposide are superior to vincristine and melphalan for pediatric metastatic rhabdomyosarcoma when administered with irradiation and combination chemotherapy: A report from the intergroup rhabdomyosarcoma study group

Philip P. Breitfeld, Elizabeth Lyden, R. Beverly Raney, Lisa A. Teot, Moody Wharam, Thom Lobe, William M. Crist, Harold M. Maurer, Sarah S. Donaldson, Frederick B. Ruymann, James R. Anderson, Richard J. Andrassy, Carola A.S. Arndt, K. Scott Baker, Frederic G. Barr, W. Archie Bleyer, Philip Breitfeld, John C. Breneman, Julia Bridge, Kenneth BrownHolcombe E. Grier, Douglas Hawkins, Peter J. Houghton, Michael Link, William H. Meyer, Jeff Michalski, Sharon Murphy, Charles N. Paidas, Alberto S. Pappo, David M. Parham, Stephen J. Qualman, Leslie Robison, Eric Sandler, Lynn Smith, Poul H.B. Sorensen, Lisa Teot, Timothy Triche, Teresa J. Vietti, David Walterhouse, Eugene S. Wiener, Suzanne Wolden, Richard Womer, Joan L. Leeson

Research output: Contribution to journalArticle

68 Citations (Scopus)

Abstract

Purpose This study was designed to estimate the partial and complete response rates (CR and PR) of two novel drug pairs (vincristine and melphalan vs. ifosfamide and etoposide) and to improve overall survival of previously untreated patients with metastatic rhabdomyosarcoma. Patients and Methods One hundred twenty-eight patients were randomly assigned to phase II window therapy consisting of vincristine and melphalan (VM-containing regimen) or ifosfamide and etoposide (IE-containing regimen). Brief window therapy (12 wks) was immediately followed-up by vincristine, dactinomycin, and cyclophosphamide (VAC), chemotherapy, surgery, and irradiation, with continuation of either VM or IE in patients with initial response. Major endpoints were initial CR and PR rates after the phase II window phase of therapy, failure-free survival (FFS), and survival. Results Patients who received the VM-containing regimen experienced significantly more anemia, neutropenia, thrombocytopenia, and had more cyclophosphamide dose reductions. The initial PR and CR rates were not significantly different for patients treated with either regimen (VM, 74%; IE, 79%;P = 0.428). However, FFS and overall survival (OS) at 3 years were significantly better with the IE-containing regimen (FFS: 33% vs. 19%;P = 0.043; OS: 55% vs. 27%;P = 0.012). Conclusions Although the VM-containing regimen produced a high response rate, inclusion of melphalan appeared to limit the cyclophosphamide dose that could be administered, and ultimately, this regimen was associated with a significantly worse outcome than was the IE-containing regimen. Also, the IE-containing regimen was associated with a gratifyingly high survival rate at 3 years (55%), which is significantly higher than has been observed on any previous Intergroup Rhabdomyosarcoma Study Group regimen for similar patients. We believe that this promising outcome indicates that this drug pair merits further randomized testing in metastatic rhabdomyosarcoma.

Original languageEnglish (US)
Pages (from-to)225-233
Number of pages9
JournalAmerican Journal of Pediatric Hematology/Oncology
Volume23
Issue number4
DOIs
StatePublished - Jan 1 2001

Fingerprint

Ifosfamide
Melphalan
Rhabdomyosarcoma
Vincristine
Etoposide
Combination Drug Therapy
Pediatrics
Survival
Cyclophosphamide
Dactinomycin
Neutropenia
Thrombocytopenia
Pharmaceutical Preparations
Anemia
Therapeutics
Survival Rate
Drug Therapy

Keywords

  • Chemotherapy
  • Children
  • Etoposide
  • Ifosfamide
  • Melphalan
  • Metastatic
  • Rhabdomyosarcoma

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Hematology
  • Oncology

Cite this

Ifosfamide and etoposide are superior to vincristine and melphalan for pediatric metastatic rhabdomyosarcoma when administered with irradiation and combination chemotherapy : A report from the intergroup rhabdomyosarcoma study group. / Breitfeld, Philip P.; Lyden, Elizabeth; Beverly Raney, R.; Teot, Lisa A.; Wharam, Moody; Lobe, Thom; Crist, William M.; Maurer, Harold M.; Donaldson, Sarah S.; Ruymann, Frederick B.; Anderson, James R.; Andrassy, Richard J.; Arndt, Carola A.S.; Scott Baker, K.; Barr, Frederic G.; Archie Bleyer, W.; Breitfeld, Philip; Breneman, John C.; Bridge, Julia; Brown, Kenneth; Grier, Holcombe E.; Hawkins, Douglas; Houghton, Peter J.; Link, Michael; Meyer, William H.; Michalski, Jeff; Murphy, Sharon; Paidas, Charles N.; Pappo, Alberto S.; Parham, David M.; Qualman, Stephen J.; Robison, Leslie; Sandler, Eric; Smith, Lynn; Sorensen, Poul H.B.; Teot, Lisa; Triche, Timothy; Vietti, Teresa J.; Walterhouse, David; Wiener, Eugene S.; Wolden, Suzanne; Womer, Richard; Leeson, Joan L.

In: American Journal of Pediatric Hematology/Oncology, Vol. 23, No. 4, 01.01.2001, p. 225-233.

Research output: Contribution to journalArticle

Breitfeld, PP, Lyden, E, Beverly Raney, R, Teot, LA, Wharam, M, Lobe, T, Crist, WM, Maurer, HM, Donaldson, SS, Ruymann, FB, Anderson, JR, Andrassy, RJ, Arndt, CAS, Scott Baker, K, Barr, FG, Archie Bleyer, W, Breitfeld, P, Breneman, JC, Bridge, J, Brown, K, Grier, HE, Hawkins, D, Houghton, PJ, Link, M, Meyer, WH, Michalski, J, Murphy, S, Paidas, CN, Pappo, AS, Parham, DM, Qualman, SJ, Robison, L, Sandler, E, Smith, L, Sorensen, PHB, Teot, L, Triche, T, Vietti, TJ, Walterhouse, D, Wiener, ES, Wolden, S, Womer, R & Leeson, JL 2001, 'Ifosfamide and etoposide are superior to vincristine and melphalan for pediatric metastatic rhabdomyosarcoma when administered with irradiation and combination chemotherapy: A report from the intergroup rhabdomyosarcoma study group', American Journal of Pediatric Hematology/Oncology, vol. 23, no. 4, pp. 225-233. https://doi.org/10.1097/00043426-200105000-00010
Breitfeld, Philip P. ; Lyden, Elizabeth ; Beverly Raney, R. ; Teot, Lisa A. ; Wharam, Moody ; Lobe, Thom ; Crist, William M. ; Maurer, Harold M. ; Donaldson, Sarah S. ; Ruymann, Frederick B. ; Anderson, James R. ; Andrassy, Richard J. ; Arndt, Carola A.S. ; Scott Baker, K. ; Barr, Frederic G. ; Archie Bleyer, W. ; Breitfeld, Philip ; Breneman, John C. ; Bridge, Julia ; Brown, Kenneth ; Grier, Holcombe E. ; Hawkins, Douglas ; Houghton, Peter J. ; Link, Michael ; Meyer, William H. ; Michalski, Jeff ; Murphy, Sharon ; Paidas, Charles N. ; Pappo, Alberto S. ; Parham, David M. ; Qualman, Stephen J. ; Robison, Leslie ; Sandler, Eric ; Smith, Lynn ; Sorensen, Poul H.B. ; Teot, Lisa ; Triche, Timothy ; Vietti, Teresa J. ; Walterhouse, David ; Wiener, Eugene S. ; Wolden, Suzanne ; Womer, Richard ; Leeson, Joan L. / Ifosfamide and etoposide are superior to vincristine and melphalan for pediatric metastatic rhabdomyosarcoma when administered with irradiation and combination chemotherapy : A report from the intergroup rhabdomyosarcoma study group. In: American Journal of Pediatric Hematology/Oncology. 2001 ; Vol. 23, No. 4. pp. 225-233.
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abstract = "Purpose This study was designed to estimate the partial and complete response rates (CR and PR) of two novel drug pairs (vincristine and melphalan vs. ifosfamide and etoposide) and to improve overall survival of previously untreated patients with metastatic rhabdomyosarcoma. Patients and Methods One hundred twenty-eight patients were randomly assigned to phase II window therapy consisting of vincristine and melphalan (VM-containing regimen) or ifosfamide and etoposide (IE-containing regimen). Brief window therapy (12 wks) was immediately followed-up by vincristine, dactinomycin, and cyclophosphamide (VAC), chemotherapy, surgery, and irradiation, with continuation of either VM or IE in patients with initial response. Major endpoints were initial CR and PR rates after the phase II window phase of therapy, failure-free survival (FFS), and survival. Results Patients who received the VM-containing regimen experienced significantly more anemia, neutropenia, thrombocytopenia, and had more cyclophosphamide dose reductions. The initial PR and CR rates were not significantly different for patients treated with either regimen (VM, 74{\%}; IE, 79{\%};P = 0.428). However, FFS and overall survival (OS) at 3 years were significantly better with the IE-containing regimen (FFS: 33{\%} vs. 19{\%};P = 0.043; OS: 55{\%} vs. 27{\%};P = 0.012). Conclusions Although the VM-containing regimen produced a high response rate, inclusion of melphalan appeared to limit the cyclophosphamide dose that could be administered, and ultimately, this regimen was associated with a significantly worse outcome than was the IE-containing regimen. Also, the IE-containing regimen was associated with a gratifyingly high survival rate at 3 years (55{\%}), which is significantly higher than has been observed on any previous Intergroup Rhabdomyosarcoma Study Group regimen for similar patients. We believe that this promising outcome indicates that this drug pair merits further randomized testing in metastatic rhabdomyosarcoma.",
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TY - JOUR

T1 - Ifosfamide and etoposide are superior to vincristine and melphalan for pediatric metastatic rhabdomyosarcoma when administered with irradiation and combination chemotherapy

T2 - A report from the intergroup rhabdomyosarcoma study group

AU - Breitfeld, Philip P.

AU - Lyden, Elizabeth

AU - Beverly Raney, R.

AU - Teot, Lisa A.

AU - Wharam, Moody

AU - Lobe, Thom

AU - Crist, William M.

AU - Maurer, Harold M.

AU - Donaldson, Sarah S.

AU - Ruymann, Frederick B.

AU - Anderson, James R.

AU - Andrassy, Richard J.

AU - Arndt, Carola A.S.

AU - Scott Baker, K.

AU - Barr, Frederic G.

AU - Archie Bleyer, W.

AU - Breitfeld, Philip

AU - Breneman, John C.

AU - Bridge, Julia

AU - Brown, Kenneth

AU - Grier, Holcombe E.

AU - Hawkins, Douglas

AU - Houghton, Peter J.

AU - Link, Michael

AU - Meyer, William H.

AU - Michalski, Jeff

AU - Murphy, Sharon

AU - Paidas, Charles N.

AU - Pappo, Alberto S.

AU - Parham, David M.

AU - Qualman, Stephen J.

AU - Robison, Leslie

AU - Sandler, Eric

AU - Smith, Lynn

AU - Sorensen, Poul H.B.

AU - Teot, Lisa

AU - Triche, Timothy

AU - Vietti, Teresa J.

AU - Walterhouse, David

AU - Wiener, Eugene S.

AU - Wolden, Suzanne

AU - Womer, Richard

AU - Leeson, Joan L.

PY - 2001/1/1

Y1 - 2001/1/1

N2 - Purpose This study was designed to estimate the partial and complete response rates (CR and PR) of two novel drug pairs (vincristine and melphalan vs. ifosfamide and etoposide) and to improve overall survival of previously untreated patients with metastatic rhabdomyosarcoma. Patients and Methods One hundred twenty-eight patients were randomly assigned to phase II window therapy consisting of vincristine and melphalan (VM-containing regimen) or ifosfamide and etoposide (IE-containing regimen). Brief window therapy (12 wks) was immediately followed-up by vincristine, dactinomycin, and cyclophosphamide (VAC), chemotherapy, surgery, and irradiation, with continuation of either VM or IE in patients with initial response. Major endpoints were initial CR and PR rates after the phase II window phase of therapy, failure-free survival (FFS), and survival. Results Patients who received the VM-containing regimen experienced significantly more anemia, neutropenia, thrombocytopenia, and had more cyclophosphamide dose reductions. The initial PR and CR rates were not significantly different for patients treated with either regimen (VM, 74%; IE, 79%;P = 0.428). However, FFS and overall survival (OS) at 3 years were significantly better with the IE-containing regimen (FFS: 33% vs. 19%;P = 0.043; OS: 55% vs. 27%;P = 0.012). Conclusions Although the VM-containing regimen produced a high response rate, inclusion of melphalan appeared to limit the cyclophosphamide dose that could be administered, and ultimately, this regimen was associated with a significantly worse outcome than was the IE-containing regimen. Also, the IE-containing regimen was associated with a gratifyingly high survival rate at 3 years (55%), which is significantly higher than has been observed on any previous Intergroup Rhabdomyosarcoma Study Group regimen for similar patients. We believe that this promising outcome indicates that this drug pair merits further randomized testing in metastatic rhabdomyosarcoma.

AB - Purpose This study was designed to estimate the partial and complete response rates (CR and PR) of two novel drug pairs (vincristine and melphalan vs. ifosfamide and etoposide) and to improve overall survival of previously untreated patients with metastatic rhabdomyosarcoma. Patients and Methods One hundred twenty-eight patients were randomly assigned to phase II window therapy consisting of vincristine and melphalan (VM-containing regimen) or ifosfamide and etoposide (IE-containing regimen). Brief window therapy (12 wks) was immediately followed-up by vincristine, dactinomycin, and cyclophosphamide (VAC), chemotherapy, surgery, and irradiation, with continuation of either VM or IE in patients with initial response. Major endpoints were initial CR and PR rates after the phase II window phase of therapy, failure-free survival (FFS), and survival. Results Patients who received the VM-containing regimen experienced significantly more anemia, neutropenia, thrombocytopenia, and had more cyclophosphamide dose reductions. The initial PR and CR rates were not significantly different for patients treated with either regimen (VM, 74%; IE, 79%;P = 0.428). However, FFS and overall survival (OS) at 3 years were significantly better with the IE-containing regimen (FFS: 33% vs. 19%;P = 0.043; OS: 55% vs. 27%;P = 0.012). Conclusions Although the VM-containing regimen produced a high response rate, inclusion of melphalan appeared to limit the cyclophosphamide dose that could be administered, and ultimately, this regimen was associated with a significantly worse outcome than was the IE-containing regimen. Also, the IE-containing regimen was associated with a gratifyingly high survival rate at 3 years (55%), which is significantly higher than has been observed on any previous Intergroup Rhabdomyosarcoma Study Group regimen for similar patients. We believe that this promising outcome indicates that this drug pair merits further randomized testing in metastatic rhabdomyosarcoma.

KW - Chemotherapy

KW - Children

KW - Etoposide

KW - Ifosfamide

KW - Melphalan

KW - Metastatic

KW - Rhabdomyosarcoma

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