Phase II trial of high-dose chemotherapy with autologous stem cell transplant for stage IV breast cancer with minimal metastatic disease

The purpose of this study was to assess the efficacy of high-dose chemother apy (HDC) with autologous stem cell transplant in stage IV breast cancer pa tients with minimal metastases. Eligible patients had (a) disease that coul d be resected en bloc and/or irradiated with curative intent using a single field and could, thus, be rendered as having no evidence of disease (NED); and/or (b) <5% bone marrow involvement. From September 1991 to August 1997 , 40 consecutive patients were prospectively entered on the study, Pre-HDC local treatment consisted of surgery (n = 31) and radiotherapy (XRT; n = 3) , All patients received HDC with cyclophosphamide, cisplatin, and 1,3-bis(2 -chloroethyl)-1-nitrosourea and autologous stem cell transplant, with or wi thout CD34 selection. Following HDC, 22 patients received XRT. Four patient s died of treatment-related complications. Eighteen patients developed grad e 3 nonhematological toxicities (15 lung, 2 cardiomyopathy, and 1 optic neu ritis), which resolved with therapy, Within a median follow-up of 49 (15-91 ) months, 14 patients had relapsed, Twenty-five patients (62.5%) were alive , and 22 patients (55%) were alive and free of disease. Median event-free a nd overall survivals were 43 and 77 months, respectively, In the subset of patients with one metastatic site, 17 of 24 (68%) remained relapse free. Gr ade 2 tumors, a single metastatic site, and delivery of XRT were favorable predictors of relapse-free survival in univariate but not multivariate anal yses. Inclusion of HDC, as described, in the multimodal treatment of stage IV breast cancer patients with minimal metastases is promising. These resul ts warrant prospective randomized trials with a HDC-containing arm in this patient population.