{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T15:04:46Z","timestamp":1788015886907,"version":"build-2784847793"},"reference-count":0,"publisher":"S. Karger AG","license":[{"start":{"date-parts":[[2025,5,26]],"date-time":"2025-05-26T00:00:00Z","timestamp":1748217600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2025,5,26]],"date-time":"2025-05-26T00:00:00Z","timestamp":1748217600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Liver Cancer"],"abstract":"<jats:p>Introduction: Combining systemic agents with hepatic arterial infusion chemotherapy (HAIC) has produced promising outcomes in advanced hepatocellular carcinoma (HCC). Raltitrexed, an antimetabolite recognized for its extended plasma half-life, enables shorter infusion schedules. This study aimed to assess the efficacy, safety, and potential predictive biomarkers of a therapeutic approach incorporating camrelizumab, lenvatinib, and a HAIC protocol using raltitrexed plus oxaliplatin (RALOX) in patients with intermediate to advanced HCC.\nMethods: Participants in this single-arm phase II study (NCT05003700) had Barcelona Clinic Liver Cancer (BCLC) stage B or C HCC. They received RALOX-HAIC in tandem with camrelizumab and lenvatinib for a maximum of six cycles, continuing until either disease progression or unacceptable toxicity. The primary outcome measure was the objective response rate (ORR).\nResults: Thirty-nine individuals underwent at least one tumor review after baseline. The confirmed ORR was 66.7% (95% CI, 49.8\u201380.9). The median progression-free survival was 13.8 months (95% CI, 10.5\u201320.5), and the median overall survival was 21.2 months (95% CI, 14.3\u201321.2). Grade 3-4 treatment-related adverse events occurred in 79.5% of the subjects, with the most common being decreased neutrophil count (41%), decreased platelet count (30.8%), and increased aspartate aminotransferase (23.1%). All side effects were, as anticipated, controllable, and no treatment-related deaths were reported. Serum IL2, CXCL13, and CCL19 levels significantly differed between stable disease and partial response patients (P &lt; 0.05 and |fold change| &gt; 1.5). Furthermore, risk stratification based on these three biomarkers revealed shorter progression-free survival and overall survival in high-risk versus low-risk subgroups (P &lt; 0.05). These results suggested that the serum concentrations of IL-2, CXCL13, and CCL19 emerged as potential predictors of clinical benefits under this triple-combination protocol.\nConclusion: The triple regimen of camrelizumab, lenvatinib, and RALOX-HAIC exhibited notable antitumor capabilities and acceptable tolerability in patients with advanced HCC. Moreover, baseline levels of IL-2, CXCL13, and CCL19 may function as predictive indicators of the response to this first-line therapeutic strategy.\n<\/jats:p>","DOI":"10.1159\/000546575","type":"journal-article","created":{"date-parts":[[2025,5,26]],"date-time":"2025-05-26T16:01:58Z","timestamp":1748275318000},"page":"1-21","source":"Crossref","is-referenced-by-count":8,"title":["Camrelizumab combined with Lenvatinib and RALOX-HAIC for unresectable hepatocellular carcinoma (Cal Era): a prospective, single-arm, phase II trial"],"prefix":"10.1159","author":[{"given":"Mengya","family":"Zang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyun","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7367-5701","authenticated-orcid":false,"given":"Huajin","family":"Pang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rong","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenli","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongru","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peilin","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaiyan","family":"Su","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guosheng","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanfeng","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinzhang","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"127","published-online":{"date-parts":[[2025,5,26]]},"container-title":["Liver Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/karger.com\/article-pdf\/doi\/10.1159\/000546575","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/karger.com\/article-pdf\/doi\/10.1159\/000546575","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,26]],"date-time":"2025-05-26T16:01:58Z","timestamp":1748275318000},"score":1,"resource":{"primary":{"URL":"https:\/\/karger.com\/article\/doi\/10.1159\/000546575"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,26]]},"references-count":0,"URL":"https:\/\/doi.org\/10.1159\/000546575","archive":["Portico"],"relation":{"is-supplemented-by":[{"id-type":"doi","id":"10.6084\/m9.figshare.29148413","asserted-by":"subject"}]},"ISSN":["2235-1795","1664-5553"],"issn-type":[{"value":"2235-1795","type":"print"},{"value":"1664-5553","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,26]]}}}