Hepatic arterial infusion of GEMOX plus systemic gemcitabine chemotherapy combined with lenvatinib and PD-1 inhibitor in large unresectable intrahepatic cholangiocarcinoma

Int Immunopharmacol. 2024 Oct 25:140:112872. doi: 10.1016/j.intimp.2024.112872. Epub 2024 Aug 8.

Abstract

Purpose: To assess the efficacy and safety of hepatic arterial infusion chemotherapy (HAIC) of gemcitabine and oxaliplatin (GEMOX) plus systemic gemcitabine chemotherapy (GEM-SYS) in combination with lenvatinib and programmed cell death protein-1 (PD-1) inhibitor for patients with large unresectable intrahepatic cholangiocarcinoma (uICC).

Methods: From November 2019 to December 2022, 21 large uICC patients who underwent GEMOX-HAIC (Day 1) and GEM-SYS (Day 8) (3w/cycle) combined with lenvatinib and PD-1 inhibitor were retrospectively enrolled. Local tumor response, progression-free survival (PFS), overall survival (OS), and adverse events (AEs) were analyzed. Tumor response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. AEs were evaluated by the common terminology criteria for adverse events (CTCAE) version 5.0.

Results: After a median follow-up duration of 16.0 months (range 5-43.5 months), 17 patients had died. The median OS was 19.5 months (range 9-43.5 months), and the median PFS was 6.0 months (range 2.5-38.5 months). The 1-, 2-, and 3-year OS rates were 71.4 %, 42.9 %, and 19.0 %, respectively. The 1-, 2-, and 3-year PFS rates were 33.3 %, 19.0 %, and 9.5 %, respectively. Complete response, partial response, stable disease, and progressive disease were observed in 0 (0 %), 11 (52.3 %), 5 (23.8 %), and 5 (23.8 %) patients, respectively. The disease control rate and objective response rate were 76.1 % and 52.3 %, respectively. None of the enrolled patients experienced grade 5 AEs.

Conclusions: GEMOX-HAIC plus GEM-SYS in combination with lenvatinib and PD-1 inhibitor was effective and well tolerated for patients with large uICC.

Keywords: Hepatic arterial infusion chemotherapy; Immune checkpoint inhibitor; Intrahepatic cholangiocarcinoma; Tyrosine kinase inhibitor.

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols* / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols* / therapeutic use
  • Bile Duct Neoplasms* / drug therapy
  • Bile Duct Neoplasms* / mortality
  • Cholangiocarcinoma* / drug therapy
  • Cholangiocarcinoma* / mortality
  • Deoxycytidine* / administration & dosage
  • Deoxycytidine* / analogs & derivatives
  • Deoxycytidine* / therapeutic use
  • Female
  • Gemcitabine*
  • Hepatic Artery
  • Humans
  • Immune Checkpoint Inhibitors / administration & dosage
  • Immune Checkpoint Inhibitors / adverse effects
  • Immune Checkpoint Inhibitors / therapeutic use
  • Infusions, Intra-Arterial
  • Male
  • Middle Aged
  • Organoplatinum Compounds
  • Oxaliplatin / administration & dosage
  • Oxaliplatin / therapeutic use
  • Phenylurea Compounds* / administration & dosage
  • Phenylurea Compounds* / adverse effects
  • Phenylurea Compounds* / therapeutic use
  • Programmed Cell Death 1 Receptor / antagonists & inhibitors
  • Quinolines* / administration & dosage
  • Quinolines* / adverse effects
  • Quinolines* / therapeutic use
  • Retrospective Studies

Substances

  • Deoxycytidine
  • lenvatinib
  • Quinolines
  • Gemcitabine
  • Phenylurea Compounds
  • Oxaliplatin
  • Programmed Cell Death 1 Receptor
  • PDCD1 protein, human
  • Immune Checkpoint Inhibitors
  • Organoplatinum Compounds

Supplementary concepts

  • gemcitabine-oxaliplatin regimen