Arterial Administration of DNA Crosslinking Agents with Restraint of Homologous Recombination Repair by Intravenous Low-Dose Gemcitabine Is Effective for Locally Advanced Pancreatic Cancer

Hiromu Mori; Shuichi Tanoue; Ryo Takaji; Shinya Ueda; Mika Okahara; Saori Sugi Ueda

doi:10.3390/cancers14010220

Arterial Administration of DNA Crosslinking Agents with Restraint of Homologous Recombination Repair by Intravenous Low-Dose Gemcitabine Is Effective for Locally Advanced Pancreatic Cancer

Cancers (Basel). 2022 Jan 3;14(1):220. doi: 10.3390/cancers14010220.

Authors

Hiromu Mori^{1

2}, Shuichi Tanoue^{2

3}, Ryo Takaji², Shinya Ueda^{1

4

5}, Mika Okahara^{2

5}, Saori Sugi Ueda^{6

7}

Affiliations

¹ Department of Radiology, Nagato Memorial Hospital, Saiki 876-0835, Japan.
² Department of Radiology, Faculty of Medicine, Oita University, Yufu 879-5593, Japan.
³ Department of Radiology, School of Medicine, Kurume University, Kurume 830-0011, Japan.
⁴ San-Ai Medical Center, Department of Radiology, Oita 870-1151, Japan.
⁵ Department of Radiology, Shin-Beppu Hospital, Beppu 874-8538, Japan.
⁶ Department of Gastroenterology, Shin-Beppu Hospital, Beppu 874-8538, Japan.
⁷ San-Ai Medical Center, Department of Gastroenterology, Oita 870-115, Japan.

Abstract

(1) Background: Pretreatment by Rad51-inhibitory substances such as gemcitabine followed by arterial chemotherapy using antineoplastic agents causing DNA crosslink might be more beneficial for patients with locally advanced pancreatic cancers than conventional treatments. The efficacy of arterial administration of DNA crosslinking agents with pretreatment of intravenous low-dose gemcitabine for patients with unresectable locally advanced or metastatic pancreatic cancer (LAPC or MPC) is evaluated. (2) Methods: A single-arm, single-center, institutional review board-approved prospective study was conducted between 2005 and 2015. Forty-five patients (23 LAPC, 22 MPC) were included. Patients received a weekly low dose of gemcitabine intravenously for three weeks followed by arterial administration of mitomycin C and epirubicin hydrochloride at tumor-supplying arteries on the fifth or sixth week. This treatment course was repeated at 1.5-to-2-month intervals. Overall survival (OS), local progression-free survival (LPFS), and therapeutic response were evaluated. LAPC or MPC were divided according to treatment compliance, excellent or poor (1 or 2), to subgroups L1, L2, M1, and M2. (3) Results: OS of LAPC and MPC were 23 months and 13 months, respectively. The OS of LAPC with excellent treatment compliance (subgroup L1, 10 patients) was 33 months with 31 months of LPFS, and four patients (40%) had a complete response (CR). The OS of the L1 subgroup was significantly longer than those of other subgroups L2, M1, and M2, which were 17 months, 17 months, and 8 months, respectively. As Grade 3 adverse effects, severe bone marrow suppression, interstitial pneumonitis, and hemolytic uremic syndrome were observed in six (13.0%), three (6.5%), and three (6.5%) patients, respectively. (4) Conclusions: Arterial DNA crosslinking with the systemic restraint of homologous recombination repair can be a new treatment option for LAPC.

Keywords: arterial administration of DNA crosslinking agents; homologous recombination repair; intravenous low-dose gemcitabine; locally advanced pancreatic cancer.