Patients will be continuously monitored while in the CRC. After the four day period in the Clinical 
Research Center they will be discharged. Depending on clinical status, they will either be discharged to 
the Oncology Division or home; but all patients will be asked to return at day 7 for a blood sample and a 
fluid sample. After completion of the virus vector infusions, patients will proceed with pleurodesis and/or 
chemotherapy options as clinically indicated to temporarily control their disease. 
The clinical endpoints of this study include measures of delivery and efficacy. 
Delivery endpoints include: 
1) analysis of fluid to determine if non-tumor cells are infected by the retroviral vector 
2) analysis of blood to determine if the retroviral vector is detectable in peripheral blood 
Efficacy endpoints are site specific, so each site will be described separately: 
Acites: 
1) Abdominal girth 
2) Time to reaccumulation of fluid after peracentesis 
3) CT scan of abdomen to assess tumor extent (when evaluable) 
4) Percent of tumor cells which integrate and/or express the retroviral vector (PCR,blot) 
5) Number of viable cancer cells per ml of fluid 
6) Cytologic evaluation of differentiation and apoptosis 
7) Measurement of c-fos or c-myc expression 
Pleural Effusion: 
1) Time to reaccumulation of fluid after thoracentesis 
2) Chest X-ray to assess extent of fluid and tumor 
3) Percent of tumor cells which integrate and/or express the retroviral vector (PCR,blot) 
4) Number of viable cancer cells per ml of fluid 
5) Cytologic evaluation of differentiation and apoptosis 
6) Measurement of c-fos or c-myc expression 
Carcinomatous Meningitis: 
1) Mental status 
2) Signs of increased intracranial pressure 
3) Percent of tumor cells which integrate and/or express the retroviral vector (PCR,blot) 
4) Number of viable cancer cells per ml of fluid 
5) Cytologic evaluation of differentiation and apoptosis 
6) Measurement of c-fos or c-myc expression 
These clinical endpoints may be inconclusive in terms of efficacy in the absence of a control 
populationbut will help on the assessment of toxicity. Efficacy willbe tested once the delivery endpoints 
(which may require multiple injections) are achieved. The latter are the realistic aims of this project at this 
time. "Efficacy" of the antisense vector may be invaluable since patients will be allowed to proceed with 
the standard management of their metastatic effusion (i.e. chemotherapy) after our studies are completed. 
We decided this because at this stage this project is more of an assessment of tumor cell retroviral delivery 
and felt it was ethically unjustified to withhold established palliative therapy. The sensitivity of the 
molecular studies should be able to detect integration or uptake in at least 5% of tumor or non-tumor cells. 
Followup studies will be done at 2 weeks, 4 weeks, and then every two months during the first year. 
Patients will be followed at least yearly for the rest of their lives for retroviral gene therapy safety 
monitoring. 
Recombinant DNA Research, Volume 20 
[171] 
