Selective intra-arterial mitomycin-C infusions for treatment-refractory colorectal liver metastases Journal Article
| Authors: | Sotirchos, V. S.; Silk, M. T.; Camacho, J. C.; Schatoff, E. M.; Kunin, H. S.; Alexander, E. S.; Zhao, K.; Connell, L. C.; Sofocleous, C. T.; Kemeny, N. E. |
| Article Title: | Selective intra-arterial mitomycin-C infusions for treatment-refractory colorectal liver metastases |
| Abstract: | Background: Mitomycin-C is an older drug which has a synergistic mechanism of action with irinotecan. This study evaluated the outcomes of selective intra-arterial mitomycin-C infusions in combination with bi-weekly systemic irinotecan for treatment of liver-dominant metastatic colorectal cancer (CRC) which progressed after hepatic arterial infusion (HAI) pump chemotherapy with floxuridine and at least two lines of systemic chemotherapy. Methods: An IRB-approved retrospective review of patients receiving at least two sessions of selective monthly mitomycin-C infusions in interventional radiology (IR) was performed. Anatomic and metabolic imaging was initially obtained at 4 weeks after the second infusion, and every 2–3 months thereafter. Response was evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and European Organization for Research and Treatment of Cancer (EORTC) criteria. Patient, disease and procedural parameters were recorded. Progression-free survival (PFS), liver progression-free survival (LPFS) and overall survival (OS) were assessed with Kaplan Meier methodology. Results: From January 2019 to April 2023, 46 patients underwent a total of 190 selective infusions (range 2–10; median 4). Twenty-three/46 (50%) patients had KRAS mutations and 35/46 (76.1%) had extrahepatic disease at the time of the first infusion. On initial follow-up, liver disease control was observed in 38/46 using RECIST 1.1 (82.6%; partial response 13%, stable disease 69.6%) and 26/31 using EORTC criteria (83.9%; complete response 6.5%, partial response 48.4%, stable disease 29%). Median PFS, LPFS and OS were 4.1 [95% confidence interval (CI): 3.2–4.9], 5.5 (95% CI: 2.5–8.4) and 9.6 (95% CI: 8.2–11.1) months respectively. The infusions were discontinued in 26 (56.5%) patients due to disease progression. Eighteen patients (39.1%) discontinued the infusion protocol due to toxicities/complications, including hepatic/biliary toxicity (26.1%), hepatic arterial thrombosis (15.2%) and/or pulmonary toxicity (8.7%). Conclusions: In this heavily pretreated population, addition of intra-arterial mitomycin-C was associated with initial liver disease control rates exceeding 80%. Toxicities were observed, particularly in patients with prolonged disease control who received ≥4 infusions. © AME Publishing Company. |
| Keywords: | adult; cancer chemotherapy; clinical article; treatment response; gene mutation; overall survival; disease course; fatigue; salvage therapy; bevacizumab; fluorouracil; drug withdrawal; liver transplantation; systemic therapy; follow up; progression free survival; computer assisted tomography; lung toxicity; multiple cycle treatment; bone marrow suppression; leukopenia; nausea; thrombocytopenia; carcinoembryonic antigen; retrospective study; cetuximab; irinotecan; panitumumab; pneumonia; alanine aminotransferase; alkaline phosphatase; aspartate aminotransferase; hypoalbuminemia; electronic medical record; folinic acid; drug infusion; interventional radiology; liver disease; hepatectomy; romiplostim; hyperbilirubinemia; liver function test; kaplan meier method; trastuzumab; cholecystectomy; mitomycin; oxaliplatin; stereotactic body radiation therapy; k ras protein; macrosalb tc 99m; floxuridine; percutaneous drainage; hepatic artery; cone beam computed tomography; digital subtraction angiography; colectomy; biliary tract disease; hepatic arterial infusion chemotherapy; metastatic colorectal cancer; liver arteriography; single photon emission computed tomography; hypertransaminasemia; pegfilgrastim; biloma; intrahepatic bile duct; yttrium 90; radioembolization; response evaluation criteria in solid tumors; cholangitis; treatment protocol; capecitabine plus oxaliplatin; hepatic artery thrombosis; colorectal liver metastasis; ramucirumab; human; male; female; article; pembrolizumab; durvalumab; interventional radiologist; positron emission tomography-computed tomography; primary tumor site; tipiracil plus trifluridine; arterially-directed therapies; colorectal liver metastases (clm); salvage treatments; integrated angiography computed tomography suite; interventional radiology suite |
| Journal Title: | Journal of Gastrointestinal Oncology |
| Volume: | 16 |
| Issue: | 1 |
| ISSN: | 2078-6891 |
| Publisher: | Pioneer Bioscience Publishing Company |
| Date Published: | 2025-02-28 |
| Start Page: | 92 |
| End Page: | 105 |
| Language: | English |
| DOI: | 10.21037/jgo-24-725 |
| PROVIDER: | scopus |
| PMCID: | PMC11921435 |
| PUBMED: | 40115936 |
| DOI/URL: | |
| Notes: | The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in the PDF. Corresponding MSK author is Vlasios S. Sotirchos -- Source: Scopus |
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