Phase II investigational window using carboplatin, iproplatin, ifosfamide, and epirubicin in children with untreated disseminated neuroblastoma

A Pediatric Oncology Group study

R. P. Castleberry, A. B. Cantor, A. A. Green, V. Joshi, R. L. Berkow, G. R. Buchanan, B. Leventhal, D. H. Mahoney, E. I. Smith, F. A. Hayes

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Abstract

Purpose: Children less than 1 year of age with metastatic neuroblastoma NB are at high risk of death. The need to identify new and effective chemotherapy agents is clear. A study was conducted by the Pediatric Oncology Group (POG) to determine the efficacy and safety of administering two courses of a single phase II agent before conventional treatment as a means to evaluate new agents in this setting. Patients and Methods: One hundred seventy-three eligible patients more than 1 year of age with disseminated neuroblastoma received two courses of one of the following: ifosfamide (IFOS) 2 g/m2/d for 4 days intravenously (IV) plus mesna; carboplatin (CARB) 560 mg/m2 IV over 1 hour; iproplatin (CHIP) 325 mg/m2 IV over 2 hours; or epirubicin (EPIR) 90 mg/m2 IV push. Following evaluation for response and toxicity, eligible patients were randomized to receive either cisplatin 90 mg/m2 IV on day 1, etoposide 200 mg/m2 IV on day 3, cyclophosphamide 150 mg/m2/d orally on days 7 to 13, doxorubicin 35 mg/m2 IV on day 14 (CECA), or cisplatin 40 mg/m2 IV on days 1 to 5 and etoposide 200 mg/m2 IV on days 2 to 4 alternating at 3-week intervals with cyclophosphamide 150 mg/m2/d orally on days 1 to 7 and doxorubicin 35 mg/m2 IV on day 8 (HDP/VP/CA). An additional 86 patients were randomized to receive either CECA or HDP/VP/CA without initial phase II therapy. Results: After phase II therapy, only 20% of patients experienced grade 3/4 hematopoietic toxicity. No toxic deaths occurred. Objective response rates (partial responses [PRs] plus minor responses [MRs]) following IFOS, CARB, CHIP, and EPIR were 70%, 77%, 67%, and 26%, respectively. Following phase III treatment, there was no statistically significant difference in rates of complete response (CR)/PR or progressive disease (PD), or in time to PD of patients who participated in the phase II window versus those who received only CECA or HDP/VP/CA. Conclusion: IFOS, CARB, and CHIP are efficacious in neuroblastoma, are well tolerated, and should be incorporated into primary treatment regimens. Combination regimens using these agents may be possible, since most repeat courses were given within 2 weeks. Administering phase II therapy to untreated patients with high-risk tumors provides a unique and sensitive method to assess new agents without compromising patient outcome.

Original languageEnglish (US)
Pages (from-to)1616-1620
Number of pages5
JournalJournal of Clinical Oncology
Volume12
Issue number8
StatePublished - Aug 1994

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Epirubicin
Ifosfamide
Carboplatin
Neuroblastoma
Pediatrics
Etoposide
Doxorubicin
Cyclophosphamide
Cisplatin
Therapeutics
Mesna
iproplatin
Poisons
Safety
Drug Therapy

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Phase II investigational window using carboplatin, iproplatin, ifosfamide, and epirubicin in children with untreated disseminated neuroblastoma : A Pediatric Oncology Group study. / Castleberry, R. P.; Cantor, A. B.; Green, A. A.; Joshi, V.; Berkow, R. L.; Buchanan, G. R.; Leventhal, B.; Mahoney, D. H.; Smith, E. I.; Hayes, F. A.

In: Journal of Clinical Oncology, Vol. 12, No. 8, 08.1994, p. 1616-1620.

Research output: Contribution to journalArticle

Castleberry, RP, Cantor, AB, Green, AA, Joshi, V, Berkow, RL, Buchanan, GR, Leventhal, B, Mahoney, DH, Smith, EI & Hayes, FA 1994, 'Phase II investigational window using carboplatin, iproplatin, ifosfamide, and epirubicin in children with untreated disseminated neuroblastoma: A Pediatric Oncology Group study', Journal of Clinical Oncology, vol. 12, no. 8, pp. 1616-1620.
Castleberry, R. P. ; Cantor, A. B. ; Green, A. A. ; Joshi, V. ; Berkow, R. L. ; Buchanan, G. R. ; Leventhal, B. ; Mahoney, D. H. ; Smith, E. I. ; Hayes, F. A. / Phase II investigational window using carboplatin, iproplatin, ifosfamide, and epirubicin in children with untreated disseminated neuroblastoma : A Pediatric Oncology Group study. In: Journal of Clinical Oncology. 1994 ; Vol. 12, No. 8. pp. 1616-1620.
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title = "Phase II investigational window using carboplatin, iproplatin, ifosfamide, and epirubicin in children with untreated disseminated neuroblastoma: A Pediatric Oncology Group study",
abstract = "Purpose: Children less than 1 year of age with metastatic neuroblastoma NB are at high risk of death. The need to identify new and effective chemotherapy agents is clear. A study was conducted by the Pediatric Oncology Group (POG) to determine the efficacy and safety of administering two courses of a single phase II agent before conventional treatment as a means to evaluate new agents in this setting. Patients and Methods: One hundred seventy-three eligible patients more than 1 year of age with disseminated neuroblastoma received two courses of one of the following: ifosfamide (IFOS) 2 g/m2/d for 4 days intravenously (IV) plus mesna; carboplatin (CARB) 560 mg/m2 IV over 1 hour; iproplatin (CHIP) 325 mg/m2 IV over 2 hours; or epirubicin (EPIR) 90 mg/m2 IV push. Following evaluation for response and toxicity, eligible patients were randomized to receive either cisplatin 90 mg/m2 IV on day 1, etoposide 200 mg/m2 IV on day 3, cyclophosphamide 150 mg/m2/d orally on days 7 to 13, doxorubicin 35 mg/m2 IV on day 14 (CECA), or cisplatin 40 mg/m2 IV on days 1 to 5 and etoposide 200 mg/m2 IV on days 2 to 4 alternating at 3-week intervals with cyclophosphamide 150 mg/m2/d orally on days 1 to 7 and doxorubicin 35 mg/m2 IV on day 8 (HDP/VP/CA). An additional 86 patients were randomized to receive either CECA or HDP/VP/CA without initial phase II therapy. Results: After phase II therapy, only 20{\%} of patients experienced grade 3/4 hematopoietic toxicity. No toxic deaths occurred. Objective response rates (partial responses [PRs] plus minor responses [MRs]) following IFOS, CARB, CHIP, and EPIR were 70{\%}, 77{\%}, 67{\%}, and 26{\%}, respectively. Following phase III treatment, there was no statistically significant difference in rates of complete response (CR)/PR or progressive disease (PD), or in time to PD of patients who participated in the phase II window versus those who received only CECA or HDP/VP/CA. Conclusion: IFOS, CARB, and CHIP are efficacious in neuroblastoma, are well tolerated, and should be incorporated into primary treatment regimens. Combination regimens using these agents may be possible, since most repeat courses were given within 2 weeks. Administering phase II therapy to untreated patients with high-risk tumors provides a unique and sensitive method to assess new agents without compromising patient outcome.",
author = "Castleberry, {R. P.} and Cantor, {A. B.} and Green, {A. A.} and V. Joshi and Berkow, {R. L.} and Buchanan, {G. R.} and B. Leventhal and Mahoney, {D. H.} and Smith, {E. I.} and Hayes, {F. A.}",
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T1 - Phase II investigational window using carboplatin, iproplatin, ifosfamide, and epirubicin in children with untreated disseminated neuroblastoma

T2 - A Pediatric Oncology Group study

AU - Castleberry, R. P.

AU - Cantor, A. B.

AU - Green, A. A.

AU - Joshi, V.

AU - Berkow, R. L.

AU - Buchanan, G. R.

AU - Leventhal, B.

AU - Mahoney, D. H.

AU - Smith, E. I.

AU - Hayes, F. A.

PY - 1994/8

Y1 - 1994/8

N2 - Purpose: Children less than 1 year of age with metastatic neuroblastoma NB are at high risk of death. The need to identify new and effective chemotherapy agents is clear. A study was conducted by the Pediatric Oncology Group (POG) to determine the efficacy and safety of administering two courses of a single phase II agent before conventional treatment as a means to evaluate new agents in this setting. Patients and Methods: One hundred seventy-three eligible patients more than 1 year of age with disseminated neuroblastoma received two courses of one of the following: ifosfamide (IFOS) 2 g/m2/d for 4 days intravenously (IV) plus mesna; carboplatin (CARB) 560 mg/m2 IV over 1 hour; iproplatin (CHIP) 325 mg/m2 IV over 2 hours; or epirubicin (EPIR) 90 mg/m2 IV push. Following evaluation for response and toxicity, eligible patients were randomized to receive either cisplatin 90 mg/m2 IV on day 1, etoposide 200 mg/m2 IV on day 3, cyclophosphamide 150 mg/m2/d orally on days 7 to 13, doxorubicin 35 mg/m2 IV on day 14 (CECA), or cisplatin 40 mg/m2 IV on days 1 to 5 and etoposide 200 mg/m2 IV on days 2 to 4 alternating at 3-week intervals with cyclophosphamide 150 mg/m2/d orally on days 1 to 7 and doxorubicin 35 mg/m2 IV on day 8 (HDP/VP/CA). An additional 86 patients were randomized to receive either CECA or HDP/VP/CA without initial phase II therapy. Results: After phase II therapy, only 20% of patients experienced grade 3/4 hematopoietic toxicity. No toxic deaths occurred. Objective response rates (partial responses [PRs] plus minor responses [MRs]) following IFOS, CARB, CHIP, and EPIR were 70%, 77%, 67%, and 26%, respectively. Following phase III treatment, there was no statistically significant difference in rates of complete response (CR)/PR or progressive disease (PD), or in time to PD of patients who participated in the phase II window versus those who received only CECA or HDP/VP/CA. Conclusion: IFOS, CARB, and CHIP are efficacious in neuroblastoma, are well tolerated, and should be incorporated into primary treatment regimens. Combination regimens using these agents may be possible, since most repeat courses were given within 2 weeks. Administering phase II therapy to untreated patients with high-risk tumors provides a unique and sensitive method to assess new agents without compromising patient outcome.

AB - Purpose: Children less than 1 year of age with metastatic neuroblastoma NB are at high risk of death. The need to identify new and effective chemotherapy agents is clear. A study was conducted by the Pediatric Oncology Group (POG) to determine the efficacy and safety of administering two courses of a single phase II agent before conventional treatment as a means to evaluate new agents in this setting. Patients and Methods: One hundred seventy-three eligible patients more than 1 year of age with disseminated neuroblastoma received two courses of one of the following: ifosfamide (IFOS) 2 g/m2/d for 4 days intravenously (IV) plus mesna; carboplatin (CARB) 560 mg/m2 IV over 1 hour; iproplatin (CHIP) 325 mg/m2 IV over 2 hours; or epirubicin (EPIR) 90 mg/m2 IV push. Following evaluation for response and toxicity, eligible patients were randomized to receive either cisplatin 90 mg/m2 IV on day 1, etoposide 200 mg/m2 IV on day 3, cyclophosphamide 150 mg/m2/d orally on days 7 to 13, doxorubicin 35 mg/m2 IV on day 14 (CECA), or cisplatin 40 mg/m2 IV on days 1 to 5 and etoposide 200 mg/m2 IV on days 2 to 4 alternating at 3-week intervals with cyclophosphamide 150 mg/m2/d orally on days 1 to 7 and doxorubicin 35 mg/m2 IV on day 8 (HDP/VP/CA). An additional 86 patients were randomized to receive either CECA or HDP/VP/CA without initial phase II therapy. Results: After phase II therapy, only 20% of patients experienced grade 3/4 hematopoietic toxicity. No toxic deaths occurred. Objective response rates (partial responses [PRs] plus minor responses [MRs]) following IFOS, CARB, CHIP, and EPIR were 70%, 77%, 67%, and 26%, respectively. Following phase III treatment, there was no statistically significant difference in rates of complete response (CR)/PR or progressive disease (PD), or in time to PD of patients who participated in the phase II window versus those who received only CECA or HDP/VP/CA. Conclusion: IFOS, CARB, and CHIP are efficacious in neuroblastoma, are well tolerated, and should be incorporated into primary treatment regimens. Combination regimens using these agents may be possible, since most repeat courses were given within 2 weeks. Administering phase II therapy to untreated patients with high-risk tumors provides a unique and sensitive method to assess new agents without compromising patient outcome.

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