Journal of Clinical Oncology, Vol 8, 648-656, Copyright © 1990 by American Society of Clinical Oncology
Cyclophosphamide, carmustine, and etoposide with autologous bone marrow transplantation in refractory Hodgkin's disease and non-Hodgkin's lymphoma: a dose-finding study
C Wheeler, JH Antin, WH Churchill, SE Come, BR Smith, GJ Bubley, DS Rosenthal, JM Rappaport, KA Ault and LE Schnipper
Thorndike Memorial Laboratories, Dana Research Institute, Boston, MA.
Cyclophosphamide, carmustine (BCNU), and etoposide (VP-16) (CBV) is a
widely used conditioning regimen in autologous bone marrow transplantation
(ABMT) of patients with refractory and relapsed lymphoma. However, the
maximum-tolerated dose (MTD) of these agents when used in combination has
not been systematically explored. We treated 58 patients (28 with
non-Hodgkin's lymphoma [NHL], 30 with Hodgkin's disease [HD]) at seven dose
levels of CBV. Doses were cyclophosphamide 4,500 to 7,200 mg/m2, BCNU 450
to 600 g/m2, and VP-16 1,200 to 2,000 mg/m2. The MTD was cyclophosphamide
7,200 mg/m2, BCNU 450 mg/m2, and VP-16 2,000 mg/m2. Six hundred milligrams
per square meter of BCNU was associated with five of 18 cases of
interstitial pneumonitis versus two of 40 at 450 mg/m2 (P = .02).
Treatment-related mortality was 5% at dose levels less than or equal to the
MTD and 22% at the highest dose. In this heavily pretreated patient
population, most of whom had high volume residual disease, complete
responses (CRs) to CBV and ABMT occurred in 25% of assessable patients with
NHL and 43% of patients with HD. Thirteen of 28 patients with NHL and 14 of
30 with HD remain free from disease progression with median follow-up of
212 and 215 days, respectively. CBV can be administered with acceptable
toxicity over a wide range of doses to patients with refractory and
relapsed lymphoma.
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