Phase I and II study of high-dose ifosfamide, carboplatin, and etoposide with autologous bone marrow rescue in lymphomas and solid tumors

W. H. Wilson, V. Jain, G. Bryant, K. H. Cowan, C. Carter, M. Cottler-Fox, B. Goldspiel, S. M. Steinberg, D. L. Longo, R. E. Wittes

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Abstract

Purpose: High-dose chemotherapy produces durable disease-free remissions in a minority of patients with resistant lymphomas and solid tumors. In an attempt to improve on the available regimens, ifosfamide, carboplatin, and etoposide (ICE) were selected for a new high-dose regimen because of their favorable spectrum of nonhematopoietic toxicity and evidence of synergy in in vitro systems. Patients and Methods: Forty-one patients with drug-resistant Hodgkin's and non-Hodgkin's lymphomas, and breast and testicular cancers were entered onto a phase I and II trial of a single course of ICE with autologous bone marrow rescue. Before transplantation, all patients received combination chemotherapy until maximal tumor response was achieved. Results: Patients received total doses of ifosfamide from 10 to 18 g/m2, carboplatin from 0.9 to 1.98 g/m2, and etoposide from 0.6 to 1.5 g/m2 administered during a 4- day period, with a maximum-tolerated dose (MTD) of ifosfamide 16 g/m2, carboplatin 1.8 g/m2, and etoposide 1.5 g/m2. The dose-limiting toxicities included irreversible renal, cardiac, and CNS dysfunction. There were three toxic deaths (7%), and all occurred above the MTD. Thirteen patients who were treated at the MTD tolerated the regimen well; reversible renal dysfunction and grade 2 mucositis commonly were observed. Of 23 heavily pretreated patients with persistent disease at the time of transplant, 10 (43%) achieved complete remissions (CRs) and 11 (48%) achieved partial remissions (PRs). Hodgkin's and non-Hodgkin's lymphoma patients who were treated at or below the MTD had a median potential follow-up of 11.9 months, and 12-month progression-free survivals of 62% and 48%, respectively. Conclusion: High- dose ICE with bone marrow rescue was well tolerated with a high response rate, and should be considered for further testing.

Original languageEnglish (US)
Pages (from-to)1712-1722
Number of pages11
JournalJournal of Clinical Oncology
Volume10
Issue number11
DOIs
StatePublished - Jan 1 1992

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Ifosfamide
Carboplatin
Etoposide
Lymphoma
Bone Marrow
Maximum Tolerated Dose
Neoplasms
Hodgkin Disease
Non-Hodgkin's Lymphoma
Kidney
Mucositis
Poisons
Testicular Neoplasms
Combination Drug Therapy
Disease-Free Survival
Transplantation
Breast Neoplasms
Transplants
Drug Therapy

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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Phase I and II study of high-dose ifosfamide, carboplatin, and etoposide with autologous bone marrow rescue in lymphomas and solid tumors. / Wilson, W. H.; Jain, V.; Bryant, G.; Cowan, K. H.; Carter, C.; Cottler-Fox, M.; Goldspiel, B.; Steinberg, S. M.; Longo, D. L.; Wittes, R. E.

In: Journal of Clinical Oncology, Vol. 10, No. 11, 01.01.1992, p. 1712-1722.

Research output: Contribution to journalArticle

Wilson, WH, Jain, V, Bryant, G, Cowan, KH, Carter, C, Cottler-Fox, M, Goldspiel, B, Steinberg, SM, Longo, DL & Wittes, RE 1992, 'Phase I and II study of high-dose ifosfamide, carboplatin, and etoposide with autologous bone marrow rescue in lymphomas and solid tumors', Journal of Clinical Oncology, vol. 10, no. 11, pp. 1712-1722. https://doi.org/10.1200/JCO.1992.10.11.1712
Wilson, W. H. ; Jain, V. ; Bryant, G. ; Cowan, K. H. ; Carter, C. ; Cottler-Fox, M. ; Goldspiel, B. ; Steinberg, S. M. ; Longo, D. L. ; Wittes, R. E. / Phase I and II study of high-dose ifosfamide, carboplatin, and etoposide with autologous bone marrow rescue in lymphomas and solid tumors. In: Journal of Clinical Oncology. 1992 ; Vol. 10, No. 11. pp. 1712-1722.
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abstract = "Purpose: High-dose chemotherapy produces durable disease-free remissions in a minority of patients with resistant lymphomas and solid tumors. In an attempt to improve on the available regimens, ifosfamide, carboplatin, and etoposide (ICE) were selected for a new high-dose regimen because of their favorable spectrum of nonhematopoietic toxicity and evidence of synergy in in vitro systems. Patients and Methods: Forty-one patients with drug-resistant Hodgkin's and non-Hodgkin's lymphomas, and breast and testicular cancers were entered onto a phase I and II trial of a single course of ICE with autologous bone marrow rescue. Before transplantation, all patients received combination chemotherapy until maximal tumor response was achieved. Results: Patients received total doses of ifosfamide from 10 to 18 g/m2, carboplatin from 0.9 to 1.98 g/m2, and etoposide from 0.6 to 1.5 g/m2 administered during a 4- day period, with a maximum-tolerated dose (MTD) of ifosfamide 16 g/m2, carboplatin 1.8 g/m2, and etoposide 1.5 g/m2. The dose-limiting toxicities included irreversible renal, cardiac, and CNS dysfunction. There were three toxic deaths (7{\%}), and all occurred above the MTD. Thirteen patients who were treated at the MTD tolerated the regimen well; reversible renal dysfunction and grade 2 mucositis commonly were observed. Of 23 heavily pretreated patients with persistent disease at the time of transplant, 10 (43{\%}) achieved complete remissions (CRs) and 11 (48{\%}) achieved partial remissions (PRs). Hodgkin's and non-Hodgkin's lymphoma patients who were treated at or below the MTD had a median potential follow-up of 11.9 months, and 12-month progression-free survivals of 62{\%} and 48{\%}, respectively. Conclusion: High- dose ICE with bone marrow rescue was well tolerated with a high response rate, and should be considered for further testing.",
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T1 - Phase I and II study of high-dose ifosfamide, carboplatin, and etoposide with autologous bone marrow rescue in lymphomas and solid tumors

AU - Wilson, W. H.

AU - Jain, V.

AU - Bryant, G.

AU - Cowan, K. H.

AU - Carter, C.

AU - Cottler-Fox, M.

AU - Goldspiel, B.

AU - Steinberg, S. M.

AU - Longo, D. L.

AU - Wittes, R. E.

PY - 1992/1/1

Y1 - 1992/1/1

N2 - Purpose: High-dose chemotherapy produces durable disease-free remissions in a minority of patients with resistant lymphomas and solid tumors. In an attempt to improve on the available regimens, ifosfamide, carboplatin, and etoposide (ICE) were selected for a new high-dose regimen because of their favorable spectrum of nonhematopoietic toxicity and evidence of synergy in in vitro systems. Patients and Methods: Forty-one patients with drug-resistant Hodgkin's and non-Hodgkin's lymphomas, and breast and testicular cancers were entered onto a phase I and II trial of a single course of ICE with autologous bone marrow rescue. Before transplantation, all patients received combination chemotherapy until maximal tumor response was achieved. Results: Patients received total doses of ifosfamide from 10 to 18 g/m2, carboplatin from 0.9 to 1.98 g/m2, and etoposide from 0.6 to 1.5 g/m2 administered during a 4- day period, with a maximum-tolerated dose (MTD) of ifosfamide 16 g/m2, carboplatin 1.8 g/m2, and etoposide 1.5 g/m2. The dose-limiting toxicities included irreversible renal, cardiac, and CNS dysfunction. There were three toxic deaths (7%), and all occurred above the MTD. Thirteen patients who were treated at the MTD tolerated the regimen well; reversible renal dysfunction and grade 2 mucositis commonly were observed. Of 23 heavily pretreated patients with persistent disease at the time of transplant, 10 (43%) achieved complete remissions (CRs) and 11 (48%) achieved partial remissions (PRs). Hodgkin's and non-Hodgkin's lymphoma patients who were treated at or below the MTD had a median potential follow-up of 11.9 months, and 12-month progression-free survivals of 62% and 48%, respectively. Conclusion: High- dose ICE with bone marrow rescue was well tolerated with a high response rate, and should be considered for further testing.

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