Journal of Clinical Oncology, Vol 12, 1890-1901, Copyright © 1994 by American Society of Clinical Oncology
Phase I trial of dacarbazine with cyclophosphamide, carmustine, etoposide, and autologous stem-cell transplantation in patients with lymphoma and multiple myeloma
DR Adkins, D Salzman, D Boldt, J Kuhn, R Irvin, GD Roodman, R Lyons, L Smith, CO Freytes and CF LeMaistre
University of Texas Health Science Center at San Antonio.
PURPOSE: We investigated the feasibility of escalating doses of dacarbazine
(DTIC) in combination with high-dose cyclophosphamide, carmustine, and
etoposide (CBV) given with autologous stem-cell transplantation in 33
patients with relapsed or refractory lymphoma or multiple myeloma. PATIENTS
AND METHODS: Eligible patients were treated in this phase I study with
cyclophosphamide (7.2 g/m2), carmustine (BCNU) (600 mg/m2), etoposide (2.4
g/m2), and escalating doses of DTIC (3,000 to 6,591 mg/m2) administered
either as a 2- (in 23 patients) or a 6- (in 10 patients) hour infusion to
determine the maximum-tolerated dose (MTD) of DTIC and the toxicity profile
of this combination. RESULTS: The MTD of DTIC infused over 2 hours and
given with the CBV regimen was 3,900 mg/m2, with the dose-limiting toxicity
being hypotension. Seven patients experienced transient acute hypocalcemia
in association with the DTIC infusion. Prolonging the DTIC infusion to 6
hours or administration of supplemental calcium did not allow further dose
escalation of DTIC to occur. Other non-hematologic toxicities observed with
this regimen have been reported with CBV alone. Of 25 patients assessable
for tumor response at first evaluation posttransplant, 13 (52%) were in
complete remission (CR), four (16%) were in partial remission (PR), five
(20%) had stable disease (SD), and three (12%) had progressive disease
(PROG). Of 31 patients assessable for relapse-free survival, 22 are alive
with 13 in CR, one in PR, two with SD, and six with PROG at a median
follow-up duration of 313 days (range, 35 to 749+). Treatment-related
mortality occurred in six patients (18%). CONCLUSION: The feasibility of
combining DTIC in high doses with the CBV regimen has been demonstrated.
Dose-limiting hypotension is transient and reversible when DTIC is
administered at 3,900 mg/m2 with CBV. Future trials to evaluate the effect
of the addition of DTIC to the CBV regimen on response rate and
relapse-free survival are encouraged.
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