Table 2.
Completed glioma virotherapy trials
Trial Phase | Disease | Virus and Effectors | Delivery and Dosing | Results | Median Survival, mo | Year [Reference] |
---|---|---|---|---|---|---|
I/II | Recurrent GBM | NDV-HUJ | Intrapatient dose escalation with 0.1–11 BIU + 3 cycles of 55 BIU i.v. or 2 × 11 BIU/wk i.v. | Maximum tolerated dose not reached; 1/11 CR, not durable; virus recoverable from body fluids | 7.4 | 2006 [64] |
IB | Recurrent GBM | G207: ICP6-inactivated and ICP34.5-deleted HSV | 1.5 × 108 pfu i.t. 2–5 days before surgery + 1 × 109 pfu into resection cavity | No dose-limiting toxicities; no CR or PR; immune cell infiltration posttreatment detectable | 6.6 | 2009 [58] |
I | Recurrent malignant gliomas | Reovirus | 1 × 107–1 × 109 TCID50 i.t. | Maximum tolerated dose not reached; 1/11 SD; virus shedding detectable, but not persistent | 4.8 | 2008 [72] |
I | Recurrent malignant glioma | ONYX-015: E1B and E3-deleted AdV | 1 × 107–1 × 1010 pfu into resection cavity | Maximum tolerated dose not reached; immune cell infiltration in recurrences of treated tumors | 6.2 | 2004 [60] |
I | High-grade glioma | HSV1716: ICP34.5-deleted HSV | 1 × 105 pfu into resection cavity + radio- and chemotherapy as needed | No virus-associated toxicity; 3/12 SD | n.d. | 2004 [54] |
I | Malignant glioma | HSV1716: ICP34.5-deleted HSV | 1 × 105 pfu i.t. + resection 4–9 days later | No adverse effects; 1/12 CR; viral DNA recoverable; indication for intratumoral viral replication | n.d. | 2002 [53] |
I | Recurrent malignant glioma | HSV1716: ICP34.5-deleted HSV | 1 × 105 pfu i.t + standard of care | Well tolerated; no reactivation of latent HSV | n.d. | 2000 [52] |
I | Malignant glioma | G207: ICP6-inactivated and ICP34.5-deleted HSV | 1 × 106–3 × 109 pfu i.t. | No virus-associated toxicity; viral DNA recoverable | 6.2 | 2000 [57] |
Abbreviations: BIU, billion infectious units (ie, 1 × 109 50% egg infectious dose); CR, complete response; n.d., not determined; PR, partial response; SD, stable disease; TCID50, 50% tissue cell infectious dose.