Our Solid Tumor Autologous Marrow Program Project Grant (STAMP) is designed to develop curative treatment for breast cancer, small cell lung cancer and refractory lymphoma. It is derived from the intersection of the paradigms of combination chemotherapy and marrow transplantation. The program has been an integrated basic and clinical science effort and has produced improved survival in metastatic breast and small cell lung cancer. The first project is the conduit for translation of the basic projects to the clinic. We select and apply preclinical leads to the clinic in quantitative experimental designs and parallel laboratory studies. In addition to dose, schedule and combination chemotherapy studies, we give major emphasis to the study of new agents appropriate for STAMP. The second project relates to the pharmacology of the AAs. We find that variability in cyclophosphamide pharmacokinetics has major implications for toxicity and response. We have developed new methodology for the study of cyclophosphamide biotransformation products. These and related studies of ifosfamide and thiotepa are designed to improve the safety and effectiveness of the STAMP program. We have found that cimetidine presumably inhibits detoxification of 40H CPA. Preliminary clinical pharmacokinetic studies show an increased concentration of 40H CPA, which is the activated metabolite, by the addition of cimetidine. The third project involves tumor vaccine development based on the evidence that lack of co-stimulatory factors such as, B-7 in antigen presenting cells, precludes the development of in vivo tumor immunity. The vaccine will consist of a vaccinia virus which contains the B-7 stimulatory gene along with the tumor antigen gene. Phase 1 studies will be performed in stage IV breast cancer patients and definitive studies in patients with microscopic tumor (MRT) (stage I and IIIA). The fourth project includes our minimal residual tumor (MRT) approach. The detection of MRT in patients in complete remission from STAMP has major therapeutic implications. Our preliminary studies, using keratin and other antibodies indicate that with confocol microscopy and immunofluorescence, one tumor cell in a million can be detected. Also, we will evaluate novel targets employing subtractive hybridization and palindrome PCR.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
5P01CA038493-11
Application #
2007472
Study Section
Cancer Centers and Research Programs Review Committee (CCRP)
Project Start
1985-07-01
Project End
1998-11-30
Budget Start
1996-12-01
Budget End
1997-11-30
Support Year
11
Fiscal Year
1997
Total Cost
Indirect Cost
Name
Dana-Farber Cancer Institute
Department
Type
DUNS #
149617367
City
Boston
State
MA
Country
United States
Zip Code
02215
Wheeler, C; Khurshid, A; Ibrahim, J et al. (2001) Incidence of post transplant myelodysplasia/acute leukemia in non-Hodgkin's lymphoma patients compared with Hodgkin's disease patients undergoing autologous transplantation following cyclophosphamide, carmustine, and etoposide (CBV). Leuk Lymphoma 40:499-509
Gong, J; Avigan, D; Chen, D et al. (2000) Activation of antitumor cytotoxic T lymphocytes by fusions of human dendritic cells and breast carcinoma cells. Proc Natl Acad Sci U S A 97:2715-8
Chang, M S; Sasaki, H; Campbell, M S et al. (1999) HRad17 colocalizes with NHP2L1 in the nucleolus and redistributes after UV irradiation. J Biol Chem 274:36544-9
Sehn, L H; Antin, J H; Shulman, L N et al. (1998) Primary diffuse large B-cell lymphoma of the mediastinum: outcome following high-dose chemotherapy and autologous hematopoietic cell transplantation. Blood 91:717-23
Ayash, L J; Elias, A; Ibrahim, J et al. (1998) High-dose multimodality therapy with autologous stem-cell support for stage IIIB breast carcinoma. J Clin Oncol 16:1000-7
Teicher, B A; Ara, G; Keyes, S R et al. (1998) Acute in vivo resistance in high-dose therapy. Clin Cancer Res 4:483-91
Teicher, B A; Ikebe, M; Ara, G et al. (1997) Transforming growth factor-beta 1 overexpression produces drug resistance in vivo: reversal by decorin. In Vivo 11:463-72
Gong, J; Chen, L; Chen, D et al. (1997) Induction of antigen-specific antitumor immunity with adenovirus-transduced dendritic cells. Gene Ther 4:1023-8
Wheeler, C; Eickhoff, C; Elias, A et al. (1997) High-dose cyclophosphamide, carmustine, and etoposide with autologous transplantation in Hodgkin's disease: a prognostic model for treatment outcomes. Biol Blood Marrow Transplant 3:98-106
Holden, S A; Emi, Y; Kakeji, Y et al. (1997) Host distribution and response to antitumor alkylating agents of EMT-6 tumor cells from subcutaneous tumor implants. Cancer Chemother Pharmacol 40:87-93

Showing the most recent 10 out of 87 publications