PHASE-I TRIAL OF DACARBAZINE WITH CYCLOPHOSPHAMIDE, CARMUSTINE, ETOPOSIDE, AND AUTOLOGOUS STEM-CELL TRANSPLANTATION IN PATIENTS WITH LYMPHOMA AND MULTIPLE-MYELOMA
Dr. Adkins et al., PHASE-I TRIAL OF DACARBAZINE WITH CYCLOPHOSPHAMIDE, CARMUSTINE, ETOPOSIDE, AND AUTOLOGOUS STEM-CELL TRANSPLANTATION IN PATIENTS WITH LYMPHOMA AND MULTIPLE-MYELOMA, Journal of clinical oncology, 12(9), 1994, pp. 1890-1901
Purpose: We investigated the feasibility of escalating doses of dacarb
azine (DTIC) in combination with high-dose cyclophosphamide, carmustin
e, and etoposide (CBV) given with autologous stem-cell transplantation
in 33 patients with relapsed or refractory lymphoma or multiple myelo
ma. Patients and Methods: Eligible patients were treated in this phase
I study with cyclophosphamide (7.2 g/m(2)), carmustine (BCNU) (600 mg
/m(2)), etoposide (2.4 g/m(2)), and escalating doses of DTIC (3,000 to
6,591 mg/m(2)) 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: T
he MTD of DTIC infused over 2 hours and given with the CBV regimen was
3,900 mg/m(2), with the dose-limiting toxicity being hypotension. Sev
en patients experienced transient acute hypocalcemia in association wi
th the DTIC infusion. Prolonging the DTIC infusion to 6 hours or admin
istration of supplemental calcium did not allow further dose escalatio
n of DTIC to occur. Other non-hematologic toxicities observed with thi
s 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 d
isease (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 FROG at
a median follow-up duration of 313 days (range, 35 to 749+). Treatmen
t-related mortality occurred in six patients (18%). Conclusion: The fe
asibility of combining DTIC in high doses with the CBV regimen has bee
n demonstrated. Dose-limiting hypotension is transient and reversible
when DTIC is administered at 3,900 mg/m(2) with CBV. Future trials to
evaluate the effect of the addition of DTIC to the CBV regimen on resp
onse rate and relapse-free survival are encouraged. (C) 1994 by Americ
an Society of Clinical Oncology.