Gene Therapy for Meningeal Carcinomatosis 
3.13 Phase C HStk-retro viral vector-producer cells will be injected into the right lateral 
ventricle via an Ommaya reservoir (repeat injections before GCV therapy) and into the 
lumbar subarachnoid space via a spinal catheter (repeat injections before GCV therapy). (4 
patients) 
3.14 Phase D 10 patients will be treated with the same regimen as in Phase C (or any previous 
phase if safety endpoints occur). 
3.2 Dosing Re gimen 
The dosing regimen is summerized in Table 1 1 for phases A - D. 
3.3 Risks. Hazards, and Discomforts 
3.31 Potential Surgical Complications 
Ommaya Reservoir Placement 
A CSF reservoir consists of a small bubble-type reservoir and ventricular catheter. The 
placement of the CSF reservoir is a minor and routine neurosurgical procedure. It can be done 
using either general anesthesia or local anesthesia. The procedure requires shaving the hair over 
the right frontal portion of the head, just in front of the coronal suture. The area is then prepped 
and draped in a sterile fashion. The skin is infiltrated with local anesthesia and a small incision is 
made just in front of the coronal suture and 3 cm to the right of the midline. A burr hole opening in 
the skull is made and a catheter is then placed into the lateral ventricle on that side. The catheter is 
then attached to the reservoir and the skin incision closed. The risks of this procedure are quite 
small. There is a minor risk that the catheter may damage the brain through which it passes. In 
addition, there is a small risk of infection. Patients will receive perioperative antibiotics during 
placement of the CSF reservoir. The location of the CSF reservoir will be confirmed by CT scan. 
After placement of the CSF reservoir, patients will be allowed to recover for 48 hours. 
Prior to administration of the murine producer cells, a CSF sample will be taken from the CSF 
reservoir and tested for the presence of malignant cells. 
The surgical procedure (Ommaya reservoir placement) carries a small risk of intracerebral 
or intraventricular hemorrhage which can cause loss of neurologic function, as well as the usual 
risks of anesthesia and infection with attendant non-neurological complications and death. The 
degree of risk depends on the preoperative condition of the patient and associated diseases (e.g. 
ischemic heart disease, renal failure, COPD etc.) however, die risks are generally less for minor 
procedures such as Ommaya reservoir placement under local anesthesia. 
Patients with malignant tumors have a significant predisposition to a variety of 
superimposed infections because of their state of immune suppression, as previously described. 
The probability of postoperative wound infection is also slightly increased because of the 
placement of the foreign material of the Ommaya reservoir . Antibiotic therapy (Rocephine) will be 
given as a prophylaxis during the surgical interventions and specific infections will be treated as 
needed. 
Lumbar Catheter Placement 
Percutaneous lumbar drainage of the subarachnoid space by an indwelling catheter placed at 
the bedside has been well described (16), and is a standard neurosurgical technique. The risks 
associated with CSF drainage by a small subarachnoid catheter are minimal. Some patients may 
develop a headache or backache following placement of the drain and prolonged headaches may 
develop in 1 to 5 % of patients. The headaches are usually relieved by bedrest and analgesics. If 
the headaches persist after removal of the catheter and last longer than one week it is possible to 
perform a "blood patch" (16). Catheters have been maintained for extended periods with minimal 
risk of infection. For a catheter maintained less than one week, the incidence of infection is less 
than 2 %. 
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Recombinant DNA Research, Volume 18 
