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. 2008 Oct 23;13(7):1238–1247. doi: 10.1111/j.1582-4934.2008.00563.x

Table 2.

Clinical experience of virotherapy in liver cancers

Virus Route/ phase Cancer type/patient number Doses/schedule (vp: viral particles; pfu: plaque-forming units; other therapies in italics) AE (G3/G4 episodes; DLT; most freq. AE) Antitumoural response† PD Viral end-points: gene expression, replication, shedding, and pharma-cokinetics Immune response References
Ad-d/1520 (Onyx-015; AE1B-55K, AE3B) I (IT) GI liver mets/ 19 2 × 109 to 2 × 1012 vp/ days 1, 29, 57 No DLT; fever, asthenia, chills n.a. n.a. n.a. n.a. [7]
I (HAI) CRC liver mets/11 2 × 108 to 2 × 1012 vp/ days 1, 8, 22, 50, 78; 5-FU 425 mg/m2 iv days 22, 50, 78, Leucovorin 20 mg/m2 iv days 22,50, 78 No DLT; 30 G3/G4 AE; fever, chills, transaminitis n.a. (2 PR at high doses) n.a. Q-PCR + (blood, d 4) >2 × 1011 vp; 1-5 × 106 genome/ml (d 4) All Ab (50%+ at baseline) [26]
II (HAI) CRC liver mets/27 2 × 1012 vp/ days 1, 8, 22, 50, 78; 5-FU 425 mg/m2 iv days 22,50, 78, Leucovorin 20 mg/m2 iv days 22,50, 78 27 G3/G4 AE; fever, chills, ALP ↑ 3/27 (11%) chemo-refractory: 2/24 (8%) 11/27 (41%) 6/8 Q-PCR + (blood); 5/7 viremia (genome copies) on d 4 All Ab (50%+ at baseline); TNF, IFN-γ, IL-1, IL-6, IL-10 induction [27]
I/ II (IT, HAI, IV) Liver/ 16 1.5 × 108- 1.5 × 1010 vp7days 1,2,15,16,29,30 (IT); days 1-5 (HAI, IV); 5-FU 300 mg/m2 qd x 3m, oxaleplatin 85 mg/m2 q3w (extra-hepatic cases) No DLT; fever, chills 0 (3/6 CEA ↓ >50%) 1/7 (14%) ISH, EM, HE + (Bx) n.a. [24]
II (IV then IT) HCC/ 5 1.5 × 109 vpVday 1 (IV); days 2, 15, 16, 29, 30 (IT) 3 G3/G4 AE; fever, chills 1/5 (1/5 AFP ↓) 4/5 (80%) HE, EM + (Bx); serum PCR + (disappeared after 4 hrs) All Ab (100%+ at baseline) [25]
I/ II (IT, IP) Hepatobiliary / 19 3 × 108 to 5 × 108 vp* (IT) up to 1.5 × 109vp* total; 5 × 108 vp* (IP) for ascites 6 G3/G4 AE; fever, myalgia, abd pain 1/19 (8 others have AFP↓ > 50%) 6/19 (32%) 0 CPE (urine); 2/2 bile stent PCR +; 4/4 ascites PCR + (d 1-9) All Ab (100%+ at baseline) [22]
HSV-NV 1020 (Δ1 copy ICP34.5, ΔUL24, ΔUL56) I (HAI) CRC liver mets/ 12 3 × 106 to 1 × 108 pfu No DLT; fever, nausea, headache Reduced CEA in some patients n.a. 1 PCR + (serum, saliva) n.a. [29]
II (HAI) CRC liver mets/ 21 1 × 108 pfu x 4 No significant toxicity 0 (single agent); 3/11 PR (after C/T) 11/21 n.a. n.a. [30]
VV-JX-594 (ATK, GM-CSF-express-ing) I (IT) Primary and secondary liver tumours 1 × 108 to 3 × 109 pfu Fever, chills; DLT: transient hyper-bilirubinemia 70% (Choi); 30% (RECIST) 1/10 (10%) All Q-PCR+ (serum) All ↑ Ab (21%+ at baseline); TNF, IFN-γ induction [17], [18]

Abbreviations: AE: adverse effect; DLT: dose-limiting toxicity; HCC: hepatocellular carcinoma; CRC: colorectal carcinoma; IT: intratumoural; IP: intraperitoneal; IV: intravenous; HAI: hepatic arterial infusion; EM: electron microscopy; EUS: endoscopic ultrasound; R/T: radiotherapy; C/T: chemotherapy; n.a.: non-available; ND: not done; bx: biopsy; IHC: immunohistochemistry; PCR: polychain reaction; PD: progressive disease; PR: partial response; Q-PCR: quantitative PCR; ISH: in situ hybridization; ALP: alkine phosphate; vp: viral particle and pfu: plaque-forming unit.

*

Estimated based on particle-to-pfu ratio of 20.

Antitumoural response = complete remission + PR.