Abstract
To determine the feasibility, time to progression, and event-free survival, twenty-two women with metastatic breast cancer received two cycles of high-dose chemotherapy (HDCT) followed by peripheral blood stem cell transplantation (PBSCT) early after first-line induction chemotherapy. The median age of the ten (45.5%) pre- and 12 (54.5%) postmenopausal women was 48 (range: 33–60) years. Sixteen patients (72.7%) had at least two or more metastatic sites involved. Protocol induction and mobilization chemotherapy including granulocyte-colony stimulating-factor (G-CSF) consisted of two cycles with adriamycin (60 mg/m2) i.v. and paclitaxel (200 mg/m2) i.v. After collection of at least 4×106/kg bodyweight peripheral blood stem cells, the first HDCT-course of adriamycin (60 mg/m2), paclitaxel (200 mg/m2) cyclophosphamide (4 g/m2), and thiotepa (800 mg/m2) (ATCT) was given to at least stable disease (SD) patients. Six to eight weeks later, the second HDCT-ATCT was administered. Each HDCT-cycle was followed by PBSCT with a median of 3.81×106/kg bodyweight CD-34 positive cells (range: 1.85–10.38). All women showed median leukocyte engraftment (>1,000×109/l) on day +9.4 (range: 7–13) and median platelet engraftment (>20,000×109/l) on day +12.3 (range: 8–15). There were no apparent differences in the clinical course and non-hematologic toxicity between the two HDCT-cycles. Of the 21 patients evaluable for response, eight (38.1%) patients achieved complete remission (CR), ten (47.6%) patients showed a partial remission (PR), two patients (9.5%) no change, and one patient (4.8%) progressive disease. After a median observation time of 36 (range 28–55) months, six (28.6%) women are alive, four (19.0%) of them in continuous CR, including two women with stable bone lesions, respectively, and 15 (71.4%) died due to progressive disease. Median time to progression (TTP) was 8 (range 4–19) months. A high initial response rate of early HDCT, including the most active drugs adriamycin and paclitaxel, can be achieved with tolerable toxicity in metastatic breast cancer. New approaches for maintaining primary tumor response achieved with efficacious high-dose chemotherapy are warranted.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Antman KH, Rowlings PA, Vaughan WP, et al (1997) High-dose chemotherapy with autologous hematopoetic stem cell support for breast cancer in North America. J Clin Oncol 15:1870–1879
Stadtmauer EA, O'Neill A, Goldstein LJ, et al (2000) Conventional dose chemotherapy compared with high dose chemotherapy plus autologous hematopoetic stem-cell transplantation. N Engl J Med 324:1069–1076
Lotz JP, Cure H, Janvier H, et al (1999) High-dose chemotherapy (HD-CT) with hematopoetic stem cell transplantation (HSCT) for metastatic breast cancer (MBC): results of the French protocol PEGASE 04. Proc Am Soc Clin Oncol 18:161 [abstr]
Mandan B, Broadwater G, Rubin P, et al (2000) Improved survival with consolidation high-dose cyclophosphamide, cisplatin and carmustin (HD-CPB) compared with observation in women with metastatic breast cancer (MBC) and only bone metastases treated with induction adriamycin, 5-fluorouracil, and methotrexate (AFM): a phase III prospective randomized comparative trial. Proc Am Soc Clin Oncol 19:184 [abstr]
Berry DA, Broadwater G, Klein JP, et al (2002) High-dose versus standard chemotherapy in metastatic breast cancer: comparison of Cancer and Leukemia Group B trials with data from the Autologous Blood and Marrow Transplant Registry. J Clin Oncol 20:743–750
Tomiak E, Piccart M, Mignolet B, et al (1996) Characterisation of complete responders to combination chemotherapy for advanced breast cancer: a retrospective EORTC Breast Group study. Eur J Cancer 32:1876–1887
Perez EA, Vogel CL, Irwin DA, Kirsher JJ, Patel R (2001) Multicenter Phase II trial of weekly paclitaxel in women with metastatic breast cancer. J Clin Oncol 19:4216–4223
Budmann DR, Berry DA, Cirrincione CT, et al (1998) Dose and dose-intensity as determinants of outcome in the adjuvant treatment of breast cancer. The cancer and leukemia Group B. J Natl Cancer Inst 90:1205–1211
Fumoleau P, Bremond A, Kerbrat P, et al (1999) Better outcome of premenopausal node positive breast cancer patients treated with six cycles vs. three cycles of adjuvant chemotherapy: eight year follow up results of FASG01. Proc Am Soc Clin Oncol 18:67 [abstr 252]
Nabholtz JM, Gelmon K, Bontenbal M, et al (1996) Multicenter, randomized comparative study of two doses of paclitaxel in patients with metastatic breast cancer. J Clin Oncol 14:1858–1867
Paridaens R, Biganzoli L, Bruning P, et al (2000) Paclitaxel versus doxorubicin as first-line single-agent chemotherapy for metastatic breast cancer: a European Organization for Research and Treatment of Cancer Randomized Study with cross-over. J Clin Oncol 18:724–733
Sayer HG, Kath R, Vogt T, et al (2000) Efficacy of a fixed low dose G-CSF in reconstitution of hematopoiesis after double autologous blood stem cell transplantation in solid tumors. Blood 96 [Suppl]:11
Vogel W, Kunert C, Blumenstengel K, et al (1998) Correlation between granulocyte/macrophage-colony-forming units and CD-34 + cells in apheresis products from patients treated with different chemotherapy regimens and granulocyte-colony-stimulating factor to mobilize periheral blood progenitor cell. J Cancer Res Clin Oncol 24:341–345
Rahman Z, Champlin R, Rondon G, et al (1997) Phase I/II study of dose-intense doxorubicin/paclitaxel/cyclophosphamide with peripheral blood progenitor cells and cytokine support in patients with metastatic breast cancer. Semin Oncol 24 [Suppl 17]:77–80
Gianni L (2002) High-dose chemotherapy for breast cancer: any use for it? Ann Oncol 13:650–652
Gianni L, Munzone E, Capri G, et al (1995) Paclitaxel by 3-hour infusion in combination with bolus doxorubicin in women with untreated metastatic breast cancer: high antitumor efficacy and cardiac effects in a dose-finding and sequence-finding study. J Clin Oncol 11:2688–2699
O'Shaughnessy J, Miles D, Vukelja S, et al (2002) Superior survival with capecitabine plus docetaxel combination therapy in anthracycline-pretreated patients with advanced breast cancer: phase III trial results. J Clin Oncol 20:2812–2823
de Magalhaes-Siverman, Bloom E, Lembersky B, et al (1997) High-dose chemotherapy and autologous stem cell support followed by posttransplantation doxorubicin as intial therapy for metastatic breast cancer. Clin Cancer Research 3:193–197
Schmid P, Samonigg H, Nitsch T, et al (2002) Randomized trial of upfront tandem high dose chemotherapy(HD) compared to standard chemotherapy with doxorubicin and paclitaxel (AT) in metastatic breast cancer (MBC). Proc Am Soc Clin Oncol 21:171[abstr]
Author information
Authors and Affiliations
Corresponding author
Additional information
This study was supported by Deutsche Krebshilfe
Rights and permissions
About this article
Cite this article
Sayer, H.G., Schilling, K., Vogt, T. et al. Double high-dose chemotherapy with adriamycin, paclitaxel, cyclophosphamide, and thiotepa followed by autologous peripheral blood stem cell transplantation in women with metastatic breast cancer. J Cancer Res Clin Oncol 129, 361–366 (2003). https://doi.org/10.1007/s00432-003-0449-3
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00432-003-0449-3