Comparison of double and triple high-dose chemotherapy with autologous blood stem cell transplantation in patients with metastatic breast cancer.
In patients with metastatic breast cancer (MBC), early dose intensification with multiple cycles of peripheral blood stem cell-supported high-dose chemotherapy (HDCT) seems superior to a late dose-intensification strategy. We compared the progression-free survival (PFS) and overall survival (OS) of 20 patients treated with a double (D)-HDCT regimen to 20 patients who received a triple (T)-HDCT, matched by age, estrogen receptor (ER) status, adjuvant chemotherapy, initial disease-free interval, predominant metastatic site, and number of metastatic sites. At a median follow-up of 41.5 months (range, 14-88 months) an intent-to-treat analysis showed no difference in PFS (p = 0.72) and OS (p = 0.93) between the matched patients. For all 76 patients treated within the D- or T-HDCT trial, median PFS and OS was 13 months (range, 2-78 months) and 24.5 months (range, 7-78 months), respectively. In multivariate analysis independent predictors of shorter OS included negative ER (relative risk [RR] = 3.0 [95% confidence interval (CI) 1.5-5.9]; p = 0.002), more than two metastatic sites (RR = 2.4 [95% CI 1.0-5.7]; p = 0.049) and failure to achieve complete remission/no evidence of disease (CR/NED) after HDCT (RR = 4.5 [95% CI 2.0-10.1]; p < 0.0001). These data show that early dose intensification with T-HDCT is not superior to a D-HDCT regimen in patients with MBC. ER-negative tumors, more than two metastatic sites and no CR/NED after HDCT, are associated with inferior outcome.
Department of Gynecology and Obstetrics, University of Heidelberg, Heidelberg, Germany. andreas_schneeweiss@med.uni-heidelberg.de
A
A
Schneeweiss
M
M
Hensel
R
R
Goerner
T
T
Khbeis
S
S
Hohaus
G
G
Egerer
E
E
Solomayer
R
R
Haas
E M
EM
Grischke
G
G
Bastert
A D
AD
Ho
D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000628:therapy*; D016190:Carboplatin / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D015251:Epirubicin / Q000627:therapeutic use; D005260:Female; D005500:Follow-Up Studies; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D006801:Humans; D007069:Ifosfamide / Q000627:therapeutic use; D008113:Liver Neoplasms / Q000188:drug therapy / Q000556:secondary / Q000628:therapy; D008875:Middle Aged; D017239:Paclitaxel / Q000627:therapeutic use; D012983:Soft Tissue Neoplasms / Q000188:drug therapy / Q000556:secondary / Q000628:therapy; D013852:Thiotepa / Q000627:therapeutic use; D016896:Treatment Outcome
D015251:Epirubicin; D013852:Thiotepa; D016190:Carboplatin; D017239:Paclitaxel; D007069:Ifosfamide