Abstract

This proposal outlines a series of Phase I trials testing the use of intensive doses of standard multiagent chemotherapy, multiagent chemotherapy with newer drugs, and a radiolabeled monoclonal antibody, all with autologous hematopoietic cell support (AHCS), to improve the treatment of patients with advanced or high risk breast cancer. Each trial will be accompanied by a total pharmacokinetic (PK) and pharmacodynamic analysis of each component of the treatment and various clinical outcomes. The goal os to produce an intensive multicomponent treatment regimen capable of substantial improvement in the treatment of previously incurable breast cancer. Based on eight years of prior experience with the cyclophosphamide/cisplatin/BCNU (CPA/cDDP/BCNU) combination with AHCS, we will perform Phase I trials of the combination of Taxol/CPA/cDDP, Taxol/CPA/cDDP/BCNU, and a randomized trial of CPA/cDDP/BCNU where the research arm will test administration of BCNU using a PK-directed model. These trials emphasize single drug or strategy modifications of previous regimens to allow easiest interpretation of outcome. An intensively dosed radiolabeled anti-breast cancer monoclonal antibody will also be studied. Phase II trials of the optimal of these approaches and combinations of them are proposed. Finally, a multicomponent multimodality regimen will be developed to incorporate a maximal effort to improve treatment activity in this area.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA061532-04
Application #
2443048
Study Section
Special Emphasis Panel (SRC (72))
Program Officer
Xie, Heng
Project Start
1994-09-20
Project End
1999-12-31
Budget Start
1997-07-01
Budget End
1999-12-31
Support Year
4
Fiscal Year
1997
Total Cost
Indirect Cost

  Institution

Name
University of Colorado Denver
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
065391526
City
Aurora
State
CO
Country
United States
Zip Code
80045

  Publications

Nieto, Yago; Franklin, Wilbur A; Jones, Roy B et al. (2004) Prognostic significance of occult tumor cells in the apheresis products of patients with advanced breast cancer receiving high-dose chemotherapy and autologous hematopoietic progenitor cell support. Biol Blood Marrow Transplant 10:415-25
Nieto, Yago; Nawaz, Samia; Jones, Roy B et al. (2002) Prognostic model for relapse after high-dose chemotherapy with autologous stem-cell transplantation for stage IV oligometastatic breast cancer. J Clin Oncol 20:707-18
Johnson, Timothy K; Cole, William; Quaife, Robert A et al. (2002) Biokinetics of yttrium-90--labeled huBrE-3 monoclonal antibody. Cancer 94:1240-8
Nieto, Y; Xu, X; Cagnoni, P J et al. (1999) Nonpredictable pharmacokinetic behavior of high-dose cyclophosphamide in combination with cisplatin and 1,3-bis(2-chloroethyl)-1-nitrosourea. Clin Cancer Res 5:747-51
Nieto, Y; Cagnoni, P J; Bearman, S I et al. (1999) Acute encephalopathy: a new toxicity associated with high-dose paclitaxel. Clin Cancer Res 5:501-6
Cagnoni, P J; Matthes, S; Day, T C et al. (1999) Modification of the pharmacokinetics of high-dose cyclophosphamide and cisplatin by antiemetics. Bone Marrow Transplant 24:1-4
Bearman, S I; Overmoyer, B A; Bolwell, B J et al. (1997) High-dose chemotherapy with autologous peripheral blood progenitor cell support for primary breast cancer in patients with 4-9 involved axillary lymph nodes. Bone Marrow Transplant 20:931-7
Stemmer, S M; Cagnoni, P J; Shpall, E J et al. (1996) High-dose paclitaxel, cyclophosphamide, and cisplatin with autologous hematopoietic progenitor-cell support: a phase I trial. J Clin Oncol 14:1463-72
Cagnoni, P J; Shpall, E J; Bearman, S I et al. (1996) Paclitaxel-containing high-dose chemotherapy: the University of Colorado experience. Semin Oncol 23:43-8
Bearman, S I; Shpall, E J; Jones, R B et al. (1996) High-dose chemotherapy with autologous hematopoietic progenitor cell support for metastatic and high-risk primary breast cancer. Semin Oncol 23:60-7

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