High-dose chemotherapy with peripheral blood stem cell support for stage IIIB inflammatory carcinoma of the breast.

The purpose of this study was to determine outcomes for 56 patients with inflammatory breast cancer (IBC) receiving high-dose chemotherapy (HDC) with cyclophosphamide, thiotepa and carboplatin (CTCb) with peripheral blood stem cell (PBSC) support. All patients received the same total amount of chemotherapy but there were differences in the sequence of therapy: 15 received induction chemotherapy, chemotherapy mobilization of PBSC and CTCb after surgery (adjuvant group) while 41 received induction chemotherapy with (n = 17) or without (n = 24) chemotherapy for mobilization of PBSC prior to surgery and CTCb after surgery (neoadjuvant group). Median time from diagnosis to HDC was 5.5 months (range 3.5-12.5). Fifty-one patients (91%) required admission to the hospital following HDC for a median of 11 days (range 5-25). There were two (4%) infectious deaths after HDC. Twenty-four patients (43%) have relapsed at a median of 18 months (range 8-50) from diagnosis resulting in death in 34%. The probabilities of overall (OS) and event-free survival (EFS) at 3 years for all 56 patients were 0.72 and 0.53, respectively, with a median follow-up of 44 months (range 15-76) from diagnosis. There were no differences in OS, EFS or patterns of relapse between patients in the adjuvant or neoadjuvant groups. These sequences of combined modality therapy incorporating HDC are comparable or superior to other intensive approaches for the treatment of IBC. Further improvements will be necessary to decrease systemic recurrences.

Adjuvant dose-intense chemotherapy with peripheral blood stem cell support in stage II-III breast cancer with five to nine involved axillary lymph nodes.

The purpose of this study is to determine outcomes for patients with high-risk nonmetastatic breast cancer undergoing high-dose chemotherapy with peripheral blood stem cell support. Forty-three patients with stage II-III disease, five to nine positive axillary lymph nodes, and a median age of 44 years (range, 27-60 years) were enrolled in a study that included: 1) standard dose doxorubicin, 5-fluorouracil, and methotrexate adjuvant therapy; 2) cyclophosphamide, etoposide, filgrastim, and peripheral blood stem cell harvest; and 3) high-dose cyclophosphamide, thiotepa, and carboplatin (CTCb) followed by peripheral blood stem cell infusion. All 43 patients received doxorubicin, 5-fluorouracil, and methotrexate, 42 (98%) received etoposide, and 41 (95%) received CTCb. Thirty-two patients (74%) are alive, 28 (65%) without relapse at a median of 55 months (range, 41-87 months). Two died (5%) of treatment-related causes, (subclavian catheter complication after etoposide and late radiation pneumonitis), and nine other deaths (21%) were associated with recurrent breast cancer. The probabilities of overall and event-free survival at 4 years were 0.77 and 0.67, respectively, compared with 0.82 and 0.69, respectively, for 72 similar patients with 10 or more positive axillary nodes receiving the same sequence of therapy. Thus, patients with five to nine positive axillary lymph nodes have a similar risk of failure after high-dose chemotherapy and peripheral blood stem cell support as patients with 10 or more positive axillary lymph nodes.

Mobilization and harvesting of peripheral blood stem cells: randomized evaluations of different doses of filgrastim.

The effects of different doses of filgrastim on yields of CD34+ peripheral blood stem cells were evaluated in patients with breast cancer. 55 were randomized to receive filgrastim 10, 20, 30 or 40 microg/kg/d with more CD34+ cells/kg/apheresis harvested after the three highest dose levels. 35 additional patients were randomized to receive 10 or 30 microg/ kg. The median number of CD34+ cells collected after 10 microg/ kg (n = 31) was 0.7 x 10(6)/kg/apheresis (range 0.1-4.4) as compared to 1.2 (range 0.1-6.8) after 30 microg/kg (n = 32) (P = 0.04). Among patients randomized to 10 v 30 microg/kg, more (50%) achieved > or = 5.0 x 10(6) CD34+ cells/kg and less aphereses were required to achieve > or = 2.5 x 10(6) CD34+ cells/kg after the higher dose (P = 0.04). In multivariate analyses, patients receiving 10 microg/kg (n = 31) had lower yields of CD34+ cells (P = 0.026) and had a 3.3-fold increase in the probability of not achieving > or = 5.0 x 10(6) CD34+ cells/kg as compared to patients receiving 20-40 microg/kg (n = 59). Patients who had received radiation had a 2.9-fold probability of not achieving > or = 2.5 x 10(6) CD34+ cells/kg. These data suggest that, in patients with good marrow reserves, doses of filgrastim > 10 microg/kg/d mobilized more CD34+ cells and may be useful when high numbers of CD34+ cells are desired.

Induction, mobilization of peripheral blood stem cells (PBSC), high-dose chemotherapy and PBSC infusion in patients with untreated stage IV breast cancer: outcomes by intent to treat analyses.

We investigated the outcomes of patients with breast cancer undergoing induction chemotherapy, mobilization of peripheral blood stem cells (PBSC) and high-dose chemotherapy (HDC) with PBSC infusion. One hundred and fourteen patients with untreated stage IV breast cancer, with a median age of 46 years (range 24-62), were entered on a phase II trial consisting of; (1) doxorubicin, 5-flurouracil, methotrexate (AFM) x 4 courses at 2 week intervals; (2) cyclophosphamide (4 g/m2), etoposide (600 mg/m2), cisplatin (105 mg/m2) (CEP), filgrastim (6 micrograms/kg/day) and PBSC collection; (3) cyclophosphamide (6 g/m2), thiotepa (500 mg/m2), carboplatin (800 mg/m2), (CTCb) followed by PBSC infusion. All patients received AFM, 107 (94%) received CEP, 93 (82%) received CTCb and PBSC as per protocol and 99 (87%) ultimately received HDC and PBSC. There was one infectious death after AFM and all other deaths were associated with progressive disease. Fifty-two patients (46%) are alive, 21 (18%) without progression, at a median 31 months (range 22-47). The probabilities of survival and progression-free survival at 3.5 years were 0.40 and 0.17, respectively. All 62 patients with visceral disease and/or a prior history of doxorubicin adjuvant therapy have relapsed or progressed. We conclude that the sequential administration of AFM, CEP and CTCb followed by PBSC resulted in long-term PFS only in patients who were NED, had bone-only disease or had lymph node or soft tissue disease with or without bone disease. Other strategies, aimed at improving responses to initial therapy, improving HDC regimens and/or developing immunomodulatory therapies, will be necessary to improve PFS for patients who fail doxorubicin adjuvant or who have visceral disease.