Abstract
Current treatments for metastatic breast cancer are not associated with significant survival benefits despite response rates of over 50%. High-dose therapy with autologous bone marrow transplantation (ABMT) has been investigated, particularly in North America, and prolonged survival in up to 25% of women has been reported, but with a significant treatment-related mortality. However, in patients with haematological malignancies undergoing autologous transplantation, haematopoietic reconstruction is significantly quicker and mortality lower than with ABMT, when peripheral blood progenitor cells (PBPCs) are used. In 32 women with metastatic breast cancer, we investigated the feasibility of PBPC mobilisation with high-dose cyclophosphamide and granulocyte colony-stimulating factor (G-CSF) after 12 weeks' infusional induction chemotherapy and the subsequent efficacy of the haematopoietic reconstitution after conditioning with melphalan and either etoposide or thiotepa. PBPC mobilisation was successful in 28/32 (88%) patients, and there was a rapid post-transplantation haematopoietic recovery: median time to neutrophils > 0.5 x 10(9) l-1 was 14 days and to platelets > 20 x 10(9) l-1 was 10 days. There was no procedure-related mortality, and the major morbidity was mucositis (WHO grade 3-4) in 18/32 patients (56%). In a patient group of which the majority had very poor prognostic features, the median survival from start of induction chemotherapy was 15 months. Thus, PBPC mobilisation and support of high-dose chemotherapy is feasible after infusional induction chemotherapy for patients with metastatic breast cancer, although the optimum drug combination has not yet been determined.
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Selected References
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- Antman K., Ayash L., Elias A., Wheeler C., Hunt M., Eder J. P., Teicher B. A., Critchlow J., Bibbo J., Schnipper L. E. A phase II study of high-dose cyclophosphamide, thiotepa, and carboplatin with autologous marrow support in women with measurable advanced breast cancer responding to standard-dose therapy. J Clin Oncol. 1992 Jan;10(1):102–110. doi: 10.1200/JCO.1992.10.1.102. [DOI] [PubMed] [Google Scholar]
- Bezwoda W. R., Seymour L., Dansey R. D. High-dose chemotherapy with hematopoietic rescue as primary treatment for metastatic breast cancer: a randomized trial. J Clin Oncol. 1995 Oct;13(10):2483–2489. doi: 10.1200/JCO.1995.13.10.2483. [DOI] [PubMed] [Google Scholar]
- Craig J. I., Anthony R. S., Stewart A., Thomson E. B., Gillon J., Parker A. C. Peripheral blood stem cell mobilization using high-dose cyclophosphamide and G-CSF in pretreated patients with lymphoma. Br J Haematol. 1993 Sep;85(1):210–212. doi: 10.1111/j.1365-2141.1993.tb08675.x. [DOI] [PubMed] [Google Scholar]
- Dunphy F. R., Spitzer G., Fornoff J. E., Yau J. C., Huan S. D., Dicke K. A., Buzdar A. U., Hortobagyi G. N. Factors predicting long-term survival for metastatic breast cancer patients treated with high-dose chemotherapy and bone marrow support. Cancer. 1994 Apr 15;73(8):2157–2167. doi: 10.1002/1097-0142(19940415)73:8<2157::aid-cncr2820730821>3.0.co;2-1. [DOI] [PubMed] [Google Scholar]
- Elias A. D., Mazanet R., Wheeler C., Anderson K., Ayash L., Schwartz G., Tepler I., Pap S., Pelaez J., Hunt M. GM-CSF potentiated peripheral blood progenitor cell (PBPC) collection with or without bone marrow as hematologic support of high-dose chemotherapy: two protocols. Breast Cancer Res Treat. 1991 Dec;20 (Suppl):S25–S29. doi: 10.1007/BF01908241. [DOI] [PubMed] [Google Scholar]
- Frei E., 3rd, Antman K., Teicher B., Eder P., Schnipper L. Bone marrow autotransplantation for solid tumors--prospects. J Clin Oncol. 1989 Apr;7(4):515–526. doi: 10.1200/JCO.1989.7.4.515. [DOI] [PubMed] [Google Scholar]
- Gregory W. M., Smith P., Richards M. A., Twelves C. J., Knight R. K., Rubens R. D. Chemotherapy of advanced breast cancer: outcome and prognostic factors. Br J Cancer. 1993 Nov;68(5):988–995. doi: 10.1038/bjc.1993.467. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hester J. P., Wallerstein R. O. Peripheral blood stem cell transplantation for breast cancer patients with bone marrow metastases using GM-CSF priming. Transfus Sci. 1993 Jan;14(1):65–69. doi: 10.1016/0955-3886(93)90057-2. [DOI] [PubMed] [Google Scholar]
- Hryniuk W., Bush H. The importance of dose intensity in chemotherapy of metastatic breast cancer. J Clin Oncol. 1984 Nov;2(11):1281–1288. doi: 10.1200/JCO.1984.2.11.1281. [DOI] [PubMed] [Google Scholar]
- Jackson G. H., Lennard A. L., Taylor P. R., Carey P., Angus B., Lucraft H., Evans R. G., Proctor S. J. Autologous bone marrow transplantation in poor-risk high-grade non-Hodgkin's lymphoma in first complete remission. Newcastle and Northern Lymphoma Group. Br J Cancer. 1994 Sep;70(3):501–505. doi: 10.1038/bjc.1994.335. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Jones A. L., Smith I. E., O'Brien M. E., Talbot D., Walsh G., Ramage F., Robertshaw H., Ashley S. Phase II study of continuous infusion fluorouracil with epirubicin and cisplatin in patients with metastatic and locally advanced breast cancer: an active new regimen. J Clin Oncol. 1994 Jun;12(6):1259–1265. doi: 10.1200/JCO.1994.12.6.1259. [DOI] [PubMed] [Google Scholar]
- Kritz A., Crown J. P., Motzer R. J., Reich L. M., Heller G., Moore M. P., Hamilton N., Yao T. J., Heelan R. T., Schneider J. G. Beneficial impact of peripheral blood progenitor cells in patients with metastatic breast cancer treated with high-dose chemotherapy plus granulocyte-macrophage colony-stimulating factor. A randomized trial. Cancer. 1993 Apr 15;71(8):2515–2521. doi: 10.1002/1097-0142(19930415)71:8<2515::aid-cncr2820710814>3.0.co;2-2. [DOI] [PubMed] [Google Scholar]
- Lazarus H. M., Reed M. D., Spitzer T. R., Rabaa M. S., Blumer J. L. High-dose i.v. thiotepa and cryopreserved autologous bone marrow transplantation for therapy of refractory cancer. Cancer Treat Rep. 1987 Jul-Aug;71(7-8):689–695. [PubMed] [Google Scholar]
- Myers S. E., Mick R., Williams S. F. High-dose chemotherapy with autologous stem cell rescue in women with metastatic breast cancer with involved bone marrow: a role for peripheral blood progenitor transplant. Bone Marrow Transplant. 1994 Apr;13(4):449–454. [PubMed] [Google Scholar]
- Peters W. P., Shpall E. J., Jones R. B., Olsen G. A., Bast R. C., Gockerman J. P., Moore J. O. High-dose combination alkylating agents with bone marrow support as initial treatment for metastatic breast cancer. J Clin Oncol. 1988 Sep;6(9):1368–1376. doi: 10.1200/JCO.1988.6.9.1368. [DOI] [PubMed] [Google Scholar]
- Somlo G., Doroshow J. H., Forman S. J., Leong L. A., Margolin K. A., Morgan R. J., Jr, Raschko J. W., Akman S. A., Ahn C., Nagasawa S. High-dose doxorubicin, etoposide, and cyclophosphamide with stem cell reinfusion in patients with metastatic or high-risk primary breast cancer. City of Hope Bone Marrow Oncology Team. Cancer. 1994 Mar 15;73(6):1678–1685. doi: 10.1002/1097-0142(19940315)73:6<1678::aid-cncr2820730621>3.0.co;2-u. [DOI] [PubMed] [Google Scholar]
- Tanaka J., Teicher B. A., Herman T. S., Holden S. A., Dezube B., Frei E., 3rd Etoposide with lonidamine or pentoxifylline as modulators of alkylating agent activity in vivo. Int J Cancer. 1991 Jun 19;48(4):631–637. doi: 10.1002/ijc.2910480424. [DOI] [PubMed] [Google Scholar]
- Tannir N., Spitzer G., Dicke K., Schell F., DiStefano A., Blumenschein G. Phase I-II study of high-dose mitomycin with autologous bone marrow transplantation in refractory metastatic breast cancer. Cancer Treat Rep. 1984 May;68(5):805–806. [PubMed] [Google Scholar]
- Vincent M. D., Powles T. J., Coombes R. C., McElwain T. J. Late intensification with high-dose melphalan and autologous bone marrow support in breast cancer patients responding to conventional chemotherapy. Cancer Chemother Pharmacol. 1988;21(3):255–260. doi: 10.1007/BF00262781. [DOI] [PubMed] [Google Scholar]
- van der Wall E., Nooijen W. J., Baars J. W., Holtkamp M. J., Schorangel J. H., Richel D. J., Rutgers E. J., Slaper-Cortenbach I. C., van der Schoot C. E., Rodenhuis S. High-dose carboplatin, thiotepa and cyclophosphamide (CTC) with peripheral blood stem cell support in the adjuvant therapy of high-risk breast cancer: a practical approach. Br J Cancer. 1995 Apr;71(4):857–862. doi: 10.1038/bjc.1995.165. [DOI] [PMC free article] [PubMed] [Google Scholar]
