High-dose busulfan and cyclophosphamide followed by autologous transplantation in patients with advanced breast cancer.
This study was conducted to evaluate the efficacy of high-dose busulfan (BU) and cyclophosphamide (CY) in patients undergoing autologous hematopoietic stem cell transplantation for metastatic breast cancer. Twenty-two patients with stage IV breast cancer underwent autologous marrow (n = 13), peripheral blood stem cell (PBSC) (n = 6) or marrow plus PBSC (n = 3) transplantation following BU (14-16 mg/kg) and CY (120-180 mg/kg). Of 22 patients, 18 had refractory relapse, one had primary refractory disease, two had responding relapse and one had no evidence of disease (NED) at the time of transplant. Eight patients had bone only disease, six had bone plus visceral disease, and eight had loco-regional recurrent disease. The median time for diagnosis to transplant was 1124 days (range 210-2582). Staging for evaluation of response was performed 4-6 months after transplantation. Six patients were not evaluable (NE) for response because of NED at transplant (n = 1) or early death due to transplant-related complications (n = 5) (one of RSV interstitial pneumonia, two of fungal infection and two of regimen-related toxicities) occurring at a median of 17 days (range 14-59) post-transplant. The patient who was NED at time of transplant is still NED on day 336 post-transplant. Seven of the 16 evaluable patients achieved a complete response (CR) (44%), five achieved a partial response (PR) (31%) and five had no response (NR), with an overall response rate of 75%. Five of 18 (28%) patients treated in refractory relapse, and both patients treated in responding relapse achieved a CR. Of the seven patients who achieved CR, three are alive and disease-free on days 204, 276 and 752 and three relapsed on days 209, 715 and 1127 post-transplant. One patient in CR died of aspergillus pneumonia on day 306 post-transplant. The median day to progression in five patients who achieved a PR after transplantation was 335 (range 144-507). The probabilities of survival and event-free survival (EFS) at 2 years was 0.22 and 0.15, respectively for all 22 patients. The probability of EFS at 2 years for the eight patients achieving CR (including one patient who was NED at transplant) was 0.33. The probabilities of overall survival at 2 years in patients who did and did not achieve a CR after transplantation was 0.63 and 0.14, respectively (P = 0.004). These data suggest that high-dose BU-CY followed by autologous stem cell transplantation is an effective regimen in patients with advanced breast cancer demonstrating that BU is an active agent in this disease and could be incorporated into treatment regimens requiring hematopoietic stem cell support.
Demirer
T
T
Fred Hutchinson Cancer Research Center, University of Washington School of Medicine, Seattle 98104, USA.
Buckner
C D
CD
Appelbaum
F R
FR
Clift
R
R
Storb
R
R
Myerson
D
D
Lilleby
K
K
Rowley
S
S
Bensinger
W I
WI
D000328:Adult; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage; D016026:Bone Marrow Transplantation; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000628:therapy*; D002066:Busulfan / Q000008:administration & dosage*; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage*; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008875:Middle Aged; D012008:Recurrence; D013997:Time Factors; D014182:Transplantation, Autologous
D018906:Antineoplastic Agents, Alkylating; D003520:Cyclophosphamide; D002066:Busulfan