PHASE-I TRIAL OF DACARBAZINE WITH CYCLOPHOSPHAMIDE, CARMUSTINE, ETOPOSIDE, AND AUTOLOGOUS STEM-CELL TRANSPLANTATION IN PATIENTS WITH LYMPHOMA AND MULTIPLE-MYELOMA

Citation
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
Citations number
43
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Oncology
ISSN journal
0732-183X
Volume
12
Issue
9
Year of publication
1994
Pages
1890 - 1901
Database
ISI
SICI code
0732-183X(1994)12:9<1890:PTODWC>2.0.ZU;2-4
Abstract
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.