Table 1.
Completed clinical trials of CED for human gliomas.
| Source | Drug (concentration) | Flow rate | Complications | Success/failure rate | Catheter placement |
|---|---|---|---|---|---|
| Laske | Tf-CRM107 (0.1–>1 ug/ml) | 0.5 uL/min increasing over 4 h to max of 4–10 ul/min for a total of 5 mL Infusion volumes increased up to 180 mL Infusions every 4–6 weeks until change seen | Reactive changes and edema (1 patient) | 9/15 patients >= 50% decrease in tumor volume | 1 to 3 catheters at selected sites in the tumor |
| Laske | Tf-CRM107 (0.67 ug/ml) | Up to 0.20 mL/h per catheter for 4–5 days until 40 mL delivered Second treatment 10 weeks after initial infusion | 8/44 cerebral edema 3/44 seizure |
Median survivial time 37 wks and mean survival time 45 weeks | 2 catheters at selected sites in the tumor |
| Wersall | mAb 425 | 4 ml/h for 1 h | 6/18 headache | Total median survival from diagnosis 39 week and from the start of mAb 18.5 week Expected median survival 24 week from start of therapy | 3 to 4 catheters in the tumor-bed tissue |
| Rand | IL-4 pseudomonas exotoxin (0.2 μg/ml up to 6 μg/ml) | 0.3–0.6 mL/h over a 4–8 day period (total infusion volume 30–185 mL) | 2/9 hydrocephalus 3/9 cerebral edema |
6/9 showed decreased enhancement after infusions but only one survived—the other tumors recurred | 1 to 3 catheters at selected sites in the tumor based on shortest possible route. When three were used, middle inserted into center of tumor and other two placed on opposing side adjacent to largest volume of white matter |
| Voges | HSV-1-tk | 0.025, 0.05, 0.1, 0.2, 0.4 mL/h, each at 2 h infusion time followed by 0.6 mL/h until final volume reached (30 or 60 mL) | – | Median survival time after infusion 28.1 weeks and median time to progression 8 weeks | Intracerebral |
| Weber | IL-4 pseudomonas exotoxin (6 μg/ml for 40 ml, 9 μg/ml for 40 ml, 15 μg/ml for 40 ml, or 9 μg/ml for 100 ml) | 6.94 μL/min for 40 mL groups and 17.36 μl/min for 100 mL group. Delivered over 96 h. | 26/31 seizures 10/31 (32%) cerebral edema (of those 10, 5 (50%) were serious) | Overall median survival 8.2 months with median survival of 5.8 months for GBM (highest 6-month survival for 6 μg/ml × 40 ml and 15 μg/ml × 40 ml) | 1 to 3 catheters placed intratumorally |
| Lidar | Paclitaxel (3 patients 7.2 mg/6 mL, all others 3.6 mg/6.6 mL) | 0.3 mL/h or 5 days in 24 h periods 20 cycles | 2/15 edema 1/15 hydrocephalus |
Median survival of 7.5 months | 1 catheter placed intratumorally |
| Patel | Cotara (0.5–3 mCi/cm3) | 0.18 mL/h through each catheter over 1 or 2 days (total volume 4.5–18 mL). After infusion, 0.5 mL diluent flush infused at 0.18 ml/h. 39 received first infusion, 16 received a second infusion | 10/51 brain edema (20%) | – | 1 to 2 catheters near or at center of enhancing tumor |
| Kunwar (103) | IL-13-PE38QQR (0.25–2 μg/mL for intratumoral and 0.25–1 μg/mL for intraparenchymal) | Intratumoral−0.4 or 0.54 mL/h for 48–96 h total Intraparenchymal−0.75 mL/h for 96 h to 6 days total | 27 headache (53%)—catheter placmt 6 aphasia (12%)—catheter placmt 21 headache (41%)—CED of drug 10 aphasia (20%)—CED of drug |
– | 1–2 for intratumoral and 1–3 catheters for intraparenchymal. One cohort with intratumoral placement followed by resection and then intraparenchymal administration. One cohort with intraparenchymal placement after tumor resection |
| Vogelbaum (91) | IL-13-PE38QQR (0.25 or 0.5 μg/ml) | 0.750 mL/h divided by # of catheters for 96 h | 5 deep vein thrombosis (23%) 3 peripheral edema (14%) 3 aphasia (14%) 3 convulsion (14%) |
– | 2 to 4 catheters placed intraparenchymally |
| Sampson | TP-38 (25, 50, or 100 ng/mL) | 0.4 mL/h for 50 h in each catheter (40 mL total) | Reflux and ineffective delivery in majority of patients (7/16 leak into subarachnoid space, 2/16 lead into ventricle, 4/16 pooling in necrotic area resection cavity, 3/16 successful infusion) | Overall median survival after therapy 28 weeks (20.1 for patients with residual disease and 33 for patients without residual disease) | 2 catheters placed to target residual tumor or deep white matter adjacent to areas of previously resected tumor |
| Carpentier | CpG-ODN | 0.333 mL/h for 6 h (2 mL infused total) | Seizure (5/31) | Median progression free survival 9.1 weeks and median overall survival 28 weeks | 2 catheters placed intracerebrally |
| Kunwar (88) | IL-13-PE38QQR (0.5 μg/ml) vs. Gliadel wafers | 0.75 mL/h over 96 h | 10/183 brain edema 39/183 aphasia |
Median survival 36.4 weeks compared to 35.4 weeks for gliadel wafers (for GBM confirmed group) | 2–4 catheters placed intraparenchymally |
| Bruce | Topotecan (0.02, 0.04, 0.0667, 0.1, or 0.133 mg/mL) | 200 μl/h in each catheter for 100 h (40 mL total) | 5/18 headache 5/18 seizure |
Median progression free survival 23 weeks and median overall survival 60 weeks | 2 catheters placed into enhancing tumor or adjacent brain |
| Desjardins | Polio-rhinovirus chimera | 500 μl/h over 6.5 h (3.25 mL total) | – | Median overall survival 12.5 mths compared to 11.3 mths historical and 6.6 mths NOVO-TTF-100 A treatment group | 1 catheter placed intratumorally |
| Vogelbaum (96) | Topotecan (0.067 mg/mL) | 0.396 mL/h over 96 h total (38 mL total) | – | – | 2 catheters each with 4 microcatheters; 1 placed intratumorally and 1 placed intraparenchymally |