Efficacy of oncolytic virus combined with HAIC of mFOLFOX for IMCC: A single-center, single-arm, prospective study.
Authors: Wang Tianxiao , Zang Chaoran , Zhang Yuewei , Ren Zhizhong , Liu Ying , Yang Xiaowei , Wang Yaqin 
Published: July 2024

e16265

Background: Hepatic arterial infusion chemotherapy (HAIC) is a well-established treatment for liver cancer. Our previous studies have demonstrated the effectiveness of HAIC with modified FOLFOX (mFOLFOX) for intrahepatic cholangiocarcinoma. However, intrahepatic mass-forming cholangiocarcinoma (IMCC) patients often lose the therapeutic opportunity due to obstructive jaundice caused by huge tumor compression. On the other hand, recombinant human adenovirus type 5 Injection (H101), an oncolytic virus (OVs), has direct anticancer effects and enhances cell-mediated immune responses. Therefor, this clinical study was designed to improve the prognosis of IMCC by the combination of OVs injection and HAIC. Methods: In this study, patients with unresectable IMCC and confirmed by biopsy were enrolled. H101 was used by ultrasound-guided injections 1-3 days before HAIC (a dosage of ≤10 cm, 1.0×1012 vp; ≥10 cm, 1.5×1012 vp). Then, patients were treated with HAIC, which is a night-administration regimen of 50 mg oxaliplatin plus 1.5g 5-fluorouracil and leucovorin, continuous infusion for 2-3 days. Patients received 4-6 cycles of treatment. The primary outcome was progression-free survival (PFS), the secondary outcomes were overall survival (OS), objective response rate (ORR), disease control rate (DCR), and quality of life (QOL). Efficacy assessments were conducted every four weeks following mRECIST v1.1 criteria. Quality of life was assessed by the WHOQOL-BREF scale. Results: From April 1, 2022 to February 1, 2024, 11 patients were enrolled. The median age was 57 years (range 36-73) and the mean tumor diameter was 8.6cm (range 4.3-11.7cm). The primary endpoint was met with a mPFS of 9.6 months. The mOS was 13.2 months. ORR was 36.3% (4/11), and DCR was 90.9% (10/11). CA-199 decreased from 2036.47 to 560.55 U/ml (P < 0.01). The CD8+ T cells increased significantly (306.94 VS. 448.7 cell/ul, P < 0.05), but the CD4+ T cells were with a steady tendency (425.41 VS. 583.50 cell/ul, P = 0.32). In addition, all patients were placed 1-3 biliary drains before enrollment. After OVs plus HAIC treatment, 7 patients had removed or closed their biliary tract drainage tubes, and the QOL score increased from 71.23 to 77.18. Significantly, during the puncture operation, the tumor texture became softer during the multi-cycle OVs plus HAIC treatment. It explains why the tumor pressure on the biliary tract was quickly relieved and the biliary drainage tube was removed in most enrolled IMCC patients. Conclusions: The combination of OVs injection and HAIC with mFOLFOX showed promising anti-tumor and immune-activation efficacy in IMCC. Meanwhile, this strategy has an effect on relieving the pain and malnutrition of long-term biliary drainage and improving the quality of life of patients. Even more, the OVs plus HAIC regimen may be more effective, if combined with the immune checkpoint inhibitors in the future. Clinical trial information: NCT05124002 .