In addition, each patient will serve as her own control, since we 
will be comparing the depth and duration of the nadirs post taxol 
following each dose of Taxol, during the dose escalation scheme. 
In this process, we predict that the depth and duration of the 
nadirs following each dose of Taxol will become less marked as 
the dose of Taxol is increased in each succeeding cycle, since 
the percentage of genetically-modified cells will be increasing 
through selection. This is in contrast to the depth and duration 
of the nadirs following each dose of Taxol, in the patient in 
whom no genetically-modified cells are present, would be more and 
more severe with each succeeding cycle. In addition, we will be 
comparing the cells which are genetically-modified with the MDR-1 
retroviral sequences, with the depth and duration of the nadir 
following each succeeding Taxol. This analysis should serve as 
a test of the performance of the pVMDR-1 retroviral transgene. 
The Taxol will be administered as a 24-hour continuous infusion. 
GCSF will be given as a 5 mcg/ml subcutaneous injection daily 
following completion of the administration of Taxol chemotherapy. 
Since the patients who are not transplanted with MDR-1 modified 
cells, and who are receiving Taxol, are also receiving GCSF, in 
order to make our MDR transduction program of therapy comparable 
to the programs which are being given to advanced breast cancer 
patients who have not received genetically-modified cells, we 
have decided to administer GCSF. This has been approved by the 
NIH RAC in a previous protocol (RAC #9306-044) , as well as by our 
own institutional IRB. 
Before the beginning of the Taxol post transplant therapy, the 
patients must be totally recovered from the side effects of the 
transplant, they must have a performance status of 1 or less. 
The white cell count must be greater than 4,000/cu mm, the ANC 
must be 1800/cu mm or greater, and the platelet count must be 
equal to or greater than 100,000/cu mm. The patients must be 
afebrile, and have no evidence of ongoing infection before the 
initiation of the Taxol. 
In the diagram below, we have summarized the algorithm to be used 
for dose adjustments for all subsequent Taxol courses in the case 
of Grade II or lower levels of toxicity following the first 
course of Taxol at 60 mg/m^. This provides for a rapid 
escalation of the dose with each cycle, so that tumor icidal doses 
of therapy can be reached quickly. This algorithm also provides 
for the downward adjustment of the doses in the event of Grade IV 
toxicity. Grade III toxicity mandates a stable dose. Thus, this 
plan will combine restrictions on dose in the beginning, when the 
patients will be the most sensitive, and rapid escalation of the 
dose of Taxol, as fast as the evolution of the resistance to 
Taxol in the marrow of the patients post-transplant will allow. 
Recombinant DNA Research, Volume 19 
[531] 
