Efficacy and toxicity of a CCNU-containing high-dose chemotherapy regimen followed by autologous hematopoietic cell transplantation in relapsed or refractory Hodgkin's disease.
High-dose CBV (cyclophosphamide, carmustine, and etoposide) in combination with autologous HCT achieves survival rates of approximately 50% at 5 years in recurrent or refractory Hodgkin's disease (HD). However, carmustine (BCNU) dose-dependent pulmonary toxicity occurs in 20% to 30% of patients. A decreased incidence of interstitial pneumonitis as well as a possible benefit in efficacy has been reported with lomustine (CCNU) compared to BCNU in the standard dose setting. In a dose-escalation study, we substituted CCNU for BCNU in the CBV regimen for 16 patients with HD (n = 12) or non-Hodgkin's lymphoma (n = 4). Based on the promising results, an additional 47 consecutive patients with HD were treated with the following regimen: CCNU (15 mg/kg) orally on day -6, etoposide (60 mg/kg) intravenously on day -4, and cyclophosphamide (100 mg/kg) intravenously on day -2. Peripheral blood progenitor cells and/or bone marrow were infused on day 0. With a median follow-up for the surviving patients of 3.2 years (range, 0.8-9.9 years), the 3-year overall survival rate was 57% (CI, +/-15%), event-free survival was 52% (CI, +/-14%), and freedom from progression was 68% (CI, +/-14%). There were 21 deaths, 10 due to HD. Six patients died due to respiratory failure. Interstitial pneumonitis occurred in 63% of patients and could not be correlated with prior chest radiotherapy. This regimen demonstrated survival rates similar to those of historical studies that used the CBV regimen. However, the incidence of interstitial pneumonitis was in excess of expected.
Stuart
M J
MJ
Division of Bone Marrow Transplantation, Stanford University Medical Center, California 94305-5623, USA. monic.jain@stanford.edu
Chao
N S
NS
Horning
S J
SJ
Wong
R M
RM
Negrin
R S
RS
Johnston
L J
LJ
Shizuru
J A
JA
Long
G D
GD
Blume
K G
KG
Stockerl-Goldstein
K E
KE
D000293:Adolescent; D000328:Adult; D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage* / Q000633:toxicity; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use; D002330:Carmustine / Q000008:administration & dosage / Q000633:toxicity; D002648:Child; D003520:Cyclophosphamide / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D006689:Hodgkin Disease / Q000150:complications / Q000628:therapy*; D006801:Humans; D008130:Lomustine / Q000008:administration & dosage* / Q000633:toxicity; D017563:Lung Diseases, Interstitial / Q000139:chemically induced; D008228:Lymphoma, Non-Hodgkin / Q000150:complications / Q000628:therapy; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D016879:Salvage Therapy / Q000009:adverse effects / Q000379:methods / Q000401:mortality; D033581:Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods* / Q000401:mortality; D015996:Survival Rate; D013810:Therapeutic Equivalency; D014182:Transplantation, Autologous
D018906:Antineoplastic Agents, Alkylating; D005047:Etoposide; D008130:Lomustine; D003520:Cyclophosphamide; D002330:Carmustine