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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, 2022-01, Vol.14 (1), p.220 [Peer Reviewed Journal]

2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. ;2022 by the authors. 2022 ;ISSN: 2072-6694 ;EISSN: 2072-6694 ;DOI: 10.3390/cancers14010220 ;PMID: 35008384

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Title:
Arterial Administration of DNA Crosslinking Agents with Restraint of Homologous Recombination Repair by Intravenous Low-Dose Gemcitabine Is Effective for Locally Advanced Pancreatic Cancer
Author: Mori, Hiromu ; Tanoue, Shuichi ; Takaji, Ryo ; Ueda, Shinya ; Okahara, Mika ; Ueda, Saori Sugi
Subjects: arterial administration of DNA crosslinking agents ; Arteries ; Biopsy ; Bone marrow ; Cancer therapies ; Catheters ; Cellular biology ; Chemotherapy ; Deoxyribonucleic acid ; DNA ; DNA repair ; Drug dosages ; Epirubicin ; Gemcitabine ; Hemolytic uremic syndrome ; Homologous recombination ; Homologous recombination repair ; Intravenous administration ; intravenous low-dose gemcitabine ; Intubation ; locally advanced pancreatic cancer ; Medical prognosis ; Metastases ; Metastasis ; Mitomycin ; Mitomycin C ; Pancreatic cancer ; Patients ; Pneumonitis ; Radiation ; Survival ; Tumors ; Veins & arteries
Is Part Of: Cancers, 2022-01, Vol.14 (1), p.220
Description: (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.
Publisher: Switzerland: MDPI AG
Language: English
Identifier: ISSN: 2072-6694
EISSN: 2072-6694
DOI: 10.3390/cancers14010220
PMID: 35008384
Source: Geneva Foundation Free Medical Journals at publisher websites
PubMed Central
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DOAJ Directory of Open Access Journals

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

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