HOTDGOL ABSn»CT 
E^xrtocsolt (Give wnn*^-r arri titled not to «3fl3ead 75 charactetB per Iln») 
Introduction of Chemotherapy Resistance into Normal Marrow Cells 
[Albert Deisseroth, M.D., Ph.D., Gabriel Hortobagyi, 
SIDEV CBAUMAN: IM.D.. and Richard Champlin, M.D. 
•tetient TnimbiTity; (T^wnty lines not to «Moaed 75 ctaracUrm p«r line) 
1. Patients with Stage III/IV breast cancer who have failed initial therapy or 
reinduction therapy, and who have not been previously exposed to Taxol, and 
who have measurable disease, and who have not had irradiation to greater than 
20% of marrow bearing areas. Patients must be at least partially responsive 
to chemotherapy. 
2. Age 18 to 60 years 
3. Performance status 0-2 and acceptable cardiac, renal, hepatic, and 
pulmonary functions. 
4. Breast cancer patients must have a negative bone scan and 
immunohistochemmical staining tests (Appendix G) which are negative for 
breast cancer cells. 
Tre a ta nfin h Plan; (Include dose adHustugnt^ crwnty lin— not to expsed 7S daracterm p«r Him) 
1. Breast cancer patients with disease which is only partially responsive to 
conventional dose chemotherapy will have peripheral blood stem cells harvested 
with GCSF stimulation, following administration of non ablative dose of 
cyclophosphamide (4 gms/m^). Autologous peripheral blood stem cells will be 
subjected to concentration in the COBE machine concentrator and CD34 selection in 
the CellPro Stem Cell Concentrator. One half of these CD34 selected cells will 
then be modified with a safety-modified retrovirus which carries a cDNA for the 
multidrug resistance MRNA (MDR-1). 
2. Infusion of the modified and unmodified peripheral blood stem cells will take place 
on d 0, following delivery of high dose cytoxan (1.5 g/m^ on d -8-, -7, -6), thiotepa 
(200 mg/m^ d-8,-7,-6) and BCNU (150 mg/m^ d-8,-7,-6). Mesna will be given during the 
cyclophosphamide infusion. GCSF will be administered post transplant. Benadryl 25 
mg and solucortef 100 mg will be given before bone marrow infusion to prevent 
anaphylaxis. j ■ j -j-v, 
3. Patients will receive prophylactic oral antibiotics and blood products irradiated with 
2500 rads. , , 2 a ^ 
4. Following recovery from transplant, Taxol will be given starting at 60 mg/m Cl Q ^ • 
and then be given at increasing doses each course (see Section 5.4) to tolerance given 
every three weeks, for a total of 12 courses. 
Recombinant DNA Research, Volume 19 
[521] 
