Sequential Treatment Including High-Dose Chemotherapy With Peripheral Blood Stem Cell Support in Patients With High-Risk Stage II-III Breast Cancer

Abstract

The authors determined outcomes for patients with localized high-risk breast cancer undergoing sequential outpatient treatment with conventional-dose adjuvant therapy, chemotherapy, and growth factor mobilization of peripheral blood stem cells (PBSC) and high-dose chemotherapy (HDC) with PBSC support in community cancer centers. Ninety-six patients with stage II-IIIB noninflammatory breast cancer with 10 or more positive lymph nodes and a median age of 46 years (range, 22-60 years) were treated with: 1) doxorubicin, 5-fluorouracil, and methotrexate (AFM), four courses at 2-week intervals; 2) cyclophosphamide (4 g/m2) and etoposide (600 mg/m2) (CE), followed by filgrastim (6 microg/kg per day) and PBSC harvest; and 3) cyclophosphamide (6 g/m2), thiotepa (500 mg/m2), and carboplatin (800 mg/m2) (CTCb), followed by PBSC infusion. All 96 patients received AFM, 95 (99%) received CE, and 95 (99%) received CTCb with a median hospital stay of 12 days (5-34 days) for all phases of treatment. Sixty-nine patients (72%) are alive, 55 (57%) without relapse at a median follow-up of 53 months (range, 37-77 months). One patient (1%) died of acute myeloid leukemia and all other deaths were associated with recurrent breast cancer. The probabilities of event-free survival (EFS) at 4 years for patients with or without locally advanced disease were 0.37 and 0.69, respectively (p = 0.004), and 0.71 and 0.48 for patients who were estrogen/progesterone receptor (ER/PR) positive or ER/PR negative, respectively (p = 0.016). In multivariate analyses, locally advanced disease (relative risk, 2.3; p = 0.021) and ER/PR-negative hormone receptor status (relative risk, 2.2; p = 0.014) were the only adverse risk factors for EFS identified. Patients with zero, one, or two of these adverse risk factors had 4-year EFS of 0.80, 0.56, and 0.33, respectively. The sequential administration of AFM, CE, and CTCb followed by PBSC in an outpatient community setting was well tolerated in patients with high-risk stage II-III breast cancer. More intensive or more novel treatment strategies will be required to decrease relapses in patients who have ER/PR-negative tumors and/or have locally advanced disease.

High-dose busulfan, melphalan and thiotepa as consolidation for non-inflammatory high-risk breast cancer

“…Table 6 summarizes the principal features of the reported clinical trials which include 30 or more patients with stage II (у10 lymph nodes) and stage III non-inflammatory breast cancer patients with a minimal follow-up of 2 years. [15][16][17][18][19][20][21][22] Two treatment strategies have been evaluated in these trials: HDC/ASCI either as consolidation therapy after initial conventional dose therapy 15,16,[18][19][20][21][22] or as first-line therapy. 17 As shown in Table 6, 616 high-risk non-inflammatory breast cancer patients with a median age of 44 years have been treated in phase II trials.…”

“…While a wide range of regimens and trials have evaluated this approach in metastatic disease, relatively few trials have investigated the therapeutic potential of HDC/ASCI in high-risk non-inflammatory breast cancer. [15][16][17][18][19][20][21][22] The use of STAMP-I (cyclophosphamide, carmustine and cisplatin), 15 STAMP-V (cyclophosphamide, thiotepa and carboplatin), [18][19][20][21] CAVP/CCVP (cyclophosphamide, etoposide and either cisplatin or doxorubicin) 16 and CEP (cyclophosphamide, etoposide and cisplatin) 22 has resulted in event-free survival (EFS) probabilities ranging from 0.48 to 0.72 at 3.5 years after diagnosis 16,17,19,21 or from the first day of adjuvant chemotherapy 15,18,20,22 in patients with high-risk non-inflammatory breast cancer.…”

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

“…Patients in the adjuvant group (n = 15) were referred after modified radical mastectomy and axillary lymph node dissection and received four to six courses of standard-dose doxorubicinbased chemotherapy prior to mobilization of PBSC. 24,35 After clinicopathologic determination of IBC by core biopsy and physical examination, 24 patients in the neoadjuvant group received four courses of doxorubicin-based chemotherapy prior to definitive surgery and received mobilization chemotherapy after surgery. Seventeen patients in the neoadjuvant group were treated with doxorubicin-based induction and chemotherapy mobilization prior to mastectomy.…”

“…Seventeen patients in the neoadjuvant group were treated with doxorubicin-based induction and chemotherapy mobilization prior to mastectomy. 24,35 All patients received high-dose chemotherapy with PBSC support after modified radical mastectomy and axillary lymph node dissection.…”

“…[19][20][21][22][23][24][25][26] Evaluation of HDC with stem cell support in patients with IBC is a logical extension of these studies.…”