Table 1.
Summary of clinical studies of CED in the treatment of malignant gliomas.
| Reference | Therapeutic agent | Trial phase | Diagnosis (n) | Infusion volume | Infusion rate | Treatment responders (n/total pts) |
MeST | Drug-related adverse events (rate) |
|---|---|---|---|---|---|---|---|---|
| Laske et al., 1997 [64] | Tf-CRM107 (TransMID) | I/II | GBM (9) AA (5) AO (1) |
5-180 mL | 0.24-0.6 mL/h | 9/15 | 74 wks (responders) 36 wks (non-responders) |
Seizures (27%), local toxicity (20%), transit elevation of ALT, AST (93%), mild hypoalbuminemia (80%) |
|
| ||||||||
| Weaver et al., 2003 [70] | Tf-CRM107 (TransMID) | II | Recurrent AA/GBM (44) | 5-180 mL | 0.2 mL/h/catheter 2 catheters |
12/34 | 37 wks | Symptomatic progressive cerebral edema (24%), seizure (9%) |
|
| ||||||||
| Rand et al., 2000 [65] | IL-4 PE38KDEL (NBI-3001) | I | GBM (9) | 30-185 mL | 0.3-0.6 mL/h | - | - | Headache (11%), seizures (22%), anomia (11%), dysphasia (11%), communicating hydrocephalus (22%), weakness (22%), nausea (11%) |
|
| ||||||||
| Weber et al., 2001 [66] Weber et al., 2003 [90] |
IL-4 PE38KDEL (NBI-3001) | I | GBM (25) AA (6) |
40-100 mL | - | - | Headache (45%), seizures (84%), weakness (32%), aphasia (23%), speech disorder (10%), hypoesthesia (16%), coma (10%), wound infection (10%), pyrexia (10%), nausea (23%) | |
|
| ||||||||
| Kunwar et al., 2003 [68] Kunwar et al., 2006 [61] Kunwar et al., 2007 [80] |
IL13- PE38QQR | I | MG (5) GBM (46) |
19.2-51.8 mL 72 mL |
0.4-0.54 mL/h intratumoral 0.75 mL/h intraparenchymal |
- | - | Headache (41 %), convulsion (14 %), sensory disturbance (25 %), aphasia/speech disorder (18 %), asthenia (16 %), hemiparesis (14 %), facial paresis (12 %), memory impairment (8 %), pyrexia (8 %), nausea (8 %) |
|
| ||||||||
| Vogelbaum et al., 2007 [81] | IL13- PE38QQR | I | GBM (22) anaplastic mixed OA (1) |
72 mL | 0.75 mL/h | - | - | Headache (50%), fatigue (73%), nausea (41%), convulsion (14%), confusion (14%), aphasia (14%), dyspepsia (14%), pyrexia (14%) |
|
| ||||||||
| Kunwar et al., 2010 [57] | IL13- PE38QQR | III | Recurrent GBM (296) | 72 mL | 0.75 mL/h | Not reported | 36.4 wks IL13- PE38QQR vs. 35.5 wks Gliadel wafer | Headache (0.4%), aphasia (1.2%), hemiparesis (0.8 %), Monoparesis (0.5%), hemiplegia (0.3%), gait disturbance (0.3%), coordination abnormal (0.3%), mental status changes (0.3%) |
|
| ||||||||
| Sampson et al., 2003 [91] Sampson et al., 2008 [92] |
TP-38 | I | GBM (17), AO (1), GSC (1), Metastasis (1) | 40 mL | 0.4 mL/h | - | - | Headache (47%), hemiparesis (20%), speech (20%), constitutional (20%), ocular/visual (13%), seizure (8%) |
|
| ||||||||
| Voges et al., 2003 [62] | LIPO-HSV-1-tk GCV | I/II | GBM (8) | 3.5 mL | 0.025-0.6 mL/h | 2/8 | 28.1 ± 3.0 wks | Transient worsening of motor aphasia (25%), fever (25%), leukocytosis (25%), ALT (37.5%), AST (25%), LDH (12.5%), CRP (25%) |
|
| ||||||||
| Lidar et al., 2004 [67] | Paclitaxel | I/II | GBM (13), AA/AO (1), Mixed AO (1) | 6-6.6 mL | 0.3 mL/h | 11/15 | 32.1 wks | Chemical meningitis (40%), neurological deterioration due to peritumoral edema and necrosis (20%) |
|
| ||||||||
| Pöpperl et al., 2005 [69] Tanner et al., 2007 [72] |
Paclitaxel | II | Recurrent GBM (8) | 36 mL | 0.3 mL/h | 0/8 | 42.9 wks | Temporary worsening of (pre-existing) neurological symptoms (63%), poor wound healing (25%), neurological deterioration (25%) |
|
| ||||||||
| Patel et al., 2005 [76] | 131I-chTNT-1/B mAb (Cotara) | I/II | Recurrent GBM (37) primary GBM (8) AA (6) |
4.5-18 mL | 0.18-0.72 mL/h | 1/12 | 37.9 wks | headache (14%), convulsions (6%), simple partial seizures (4%), aphasia (6%), weakness (6%), hemiparesis (14%), facial palsy (4%), short-term memory loss (2%), fatigue (6%), nausea (4%) |
|
| ||||||||
| Sampson et al., 2006 [93] | I131-Ch81C6 | Recurrent GBM (10) | 4.5-18 mL | 0.18 mL/h | 3/10 | 30.3 wks | ||
|
| ||||||||
| Pandit-Taskar et al., 2018 [77] | I124-8H9 | I | Diffuse intrinsic pontine glioma | 0.25-4 mL | 0.05-0.45 mL/h | - | - | Headache (50%), ataxia (29%), facial palsy (36%), diplopia (25%), muscle weakness (22%), dysarthria (15%), anaemia (32%), platelet count decreased (25%), white blood cells decreased (67%), ALT (32%), AST (25%), hypoalbuminaemia (61%), rash (11%), skin infection (8%), vomiting (18%) |
|
| ||||||||
| Boiardi et al., 2005 [73] | Mitoxantrone | 0 | Recurrent MG (12) | - | - | Procedure problem (25%), infection (8%) | ||
|
| ||||||||
| Carpentier et al., 2006 [63] | CpG-ODN | I | Recurrent GBM (24) | 1 mL/catheter | 0.2 mL/h/catheter | - | - | Worsening of previous neurological condition (21%), partial seizures (21%), somnolence (8%), fever (21%), fatigue (25%), nausea (4%), lymphopenia (46%), ALT (25%), AST (4%) |
|
| ||||||||
| Carpentier et al., 2010 [74] | CpG-ODN | II | Recurrent GBM (31) | 1 mL/catheter 2 catheters |
0.2 mL/h/catheter | 3/31 | 28 wks | Worsening of previous neurological condition (65%), partial seizures (42%), general seizures (16%), fever (grade 2) (3%), fatigue (grade 2) (6%), hemorrhage leading to death 8 days after treatment (3%), lymphopenia (grade 2) (71%), lymphopenia (grade 3) (48%), ALT (10%) |
|
| ||||||||
| Hau et al., 2007 [86] | TGF-β2 inhibitor Trabedersen |
I/II | AA (5) GBM (19) |
23-81 mL/cycle up to 10 cycles | 0.24-0.32 mL/h | 24 | 146.6 wks AA 44.0 wks GBM |
Serious adverse events central and peripheral nervous system disorders (92%) |
|
| ||||||||
| Bogdahn et al., 2011 [75] | TGF-β2 inhibitor Trabedersen |
IIb | Recurrent/ refractory GBM, AA (145) | 40 mL/cycle up to 11 cycles | 0.24 mL/h | Not reported | AA: 39.1 mos (10 μM) vs. 35.2 mos (80 μM) vs. 21.7 mos (TMZ or PCV) GBM: 7.3 mos (10 μM) vs. 10.9 mos (80 μM) vs. 10 mos (TMZ or PCV) |
Headache (10%), nervous system disorders (59-66%), depressed level of consciousness (4-12%), hemiparesis (22-27%), aphasia (10-15%), neurological symptom (8-17%), convulsion (8-12%), injury poisoning, and procedural complications (16-17%), infections and infestations brain abscess (7-12%), psychiatric disorders (6-12%), blood and lymphatic system disorders (5-8%) |
|
| ||||||||
| Bruce et al., 2011 [78] | Topotecan | Ib | Recurrent GBM (10), AA (2), AE (2), AO (2) | 40 mL | 0.2 mL/h | - | - | Headache (31%), seizure (31%), worsened hemiparesis (31%), right-hand dyscoordination (13%), upper-extremity weakness (6%), poor wound healing (13%), intracerebral hemorrhage (6%), thrombocytopenia/leukopenia (13%), gastrointestinal symptoms (25%) |
|
| ||||||||
| Desjardins et al., 2018 [87] | Recombinant poliovirus | II | Recurrent GBM (61) | 3.25 mL | 0.5 mL/h | - | 12.5 mos (PVSRIPO) vs. 11.3 mos (Historical control) | Headache (52%), hemiparesis (50%), seizure (45%), dysphasia (28%), cognitive disturbance (25%), hemianopia (19%), confusion (18%), paresthesia (13%), fatigue (12%), nausea (10%) |
Abbreviations. AA: anaplastic astroglioma; AE: anaplastic ependymoma; ALT: alanine aminotransferase; AST: aspartate aminotransferase; AO: anaplastic oligodendroglioma; GSC: gliosarcoma; MG: malignant glioma; n: number of patients; OA: oligoastrocytoma; pts: patients.