Julie Marie Vose

University of Nebraska Medical Center, Internal Medicine Oncology/Hematology

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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

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 (Profiled Author: Kenneth H Cowan)

Journal of Clinical Oncology 1992;10(11):1712-1722.

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/m 2 , carboplatin from 0.9 to 1.98 g/m 2 , and etoposide from 0.6 to 1.5 g/m 2 administered during a 4- day period, with a maximum-tolerated dose (MTD) of ifosfamide 16 g/m 2 , carboplatin 1.8 g/m 2 , and etoposide 1.5 g/m 2 . 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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