{
  "abstract": "Purpose\n\nVascular endothelial growth factor inhibitors (VEGFIs) are essential for the treatment of metastatic colorectal cancer (mCRC). Given the ineffectiveness of epidermal growth factor receptor inhibitors in managing RAS-mutant mCRC, long-term VEGFI therapy is often required; however, it is associated with an increased risk of proteinuria. As the use of VEGFI in later-line mCRC treatment has become more prevalent, proteinuria has emerged as a critical dose-limiting toxicity. However, its effect on the treatment outcomes remains unclear. This study examined the incidence of proteinuria during extended VEGFI use and its effect on overall survival (OS) in RAS-mutant mCRC.Methods\n\nThis single-center retrospective study analyzed patients with RAS-mutant stage IV mCRC treated with first-line VEGFIs at Gifu University Hospital. Proteinuria incidence was estimated using the Kaplan-Meier method. OS from a 12-month landmark was compared according to the occurrence of dipstick proteinuria 2+ or greater within the first year using Cox regression.Results\n\nAmong 185 patients, the Kaplan-Meier cumulative incidence of dipstick proteinuria 2+ or greater was 11%, 37%, and 45% at 1, 2, and 3 years, respectively. Of 123 patients in the 12-month landmark cohort, 13 had early-onset proteinuria. The age- and sex-adjusted HR for subsequent mortality was 1.81 (95% CI 0.84-3.86; p = 0.128).Conclusions\n\nProteinuria accumulated during extended VEGFI therapy. Early-onset proteinuria may be associated with poorer subsequent OS, although the wide confidence interval precludes a definitive conclusion. These findings underscore the importance of careful proteinuria monitoring during long-term VEGFI treatment.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Pharmacy, Gifu University Hospital, Gifu, Japan.",
    "Innovative and Clinical Research Promotion Center, Gifu University Hospital, Gifu, Japan.",
    "Department of Pharmacy, Gifu University Hospital, Gifu, Japan. fujii.hironori.u5@f.gifu-u.ac.jp.",
    "Laboratory of Advanced Medical Pharmacy, Gifu Pharmaceutical University, Gifu, Japan.",
    "Department of Surgical Oncology, Gifu University Graduate School of Medicine, Gifu, Japan.",
    "Cancer Center, Gifu University Hospital, Gifu, Japan.",
    "Patient Safety Division, Gifu University Hospital, Gifu, Japan.",
    "Laboratory of Pharmacy Practice and Social Science, Gifu Pharmaceutical University, Gifu, Japan."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 14,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Daichi Watanabe",
      "orcid": "0000-0002-5377-0901"
    },
    {
      "affs": [
        2
      ],
      "name": "Hironori Fujii"
    },
    {
      "affs": [
        3
      ],
      "name": "Yuto Miura"
    },
    {
      "affs": [
        3
      ],
      "name": "Misato Kani"
    },
    {
      "affs": [
        4
      ],
      "name": "Wakana Chikaishi"
    },
    {
      "affs": [
        4
      ],
      "name": "Jesse Yu Tajima"
    },
    {
      "affs": [
        5
      ],
      "name": "Akitaka Makiyama"
    },
    {
      "affs": [
        0
      ],
      "name": "Yunami Yamada"
    },
    {
      "affs": [
        0
      ],
      "name": "Koichi Ohata"
    },
    {
      "affs": [
        0
      ],
      "name": "Chiemi Hirose"
    },
    {
      "affs": [
        0,
        6,
        7
      ],
      "name": "Hirotoshi Iihara"
    },
    {
      "affs": [
        0,
        3
      ],
      "name": "Ryo Kobayashi"
    },
    {
      "affs": [
        4
      ],
      "name": "Nobuhisa Matsuhashi"
    },
    {
      "affs": [
        0,
        3
      ],
      "name": "Akio Suzuki"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/9n2fkprphy7ny.bib",
  "cited_by": 0,
  "doi": "10.1007/s00384-026-05210-x",
  "fulltext_url": "https://europepmc.org/articles/PMC13719852",
  "id": "9n2fkprphy7ny",
  "issns": [
    "0179-1958",
    "1432-1262"
  ],
  "landing_url": "https://europepmc.org/article/MED/42957888",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Research"
    ],
    [
      "openalex",
      "2730|Colorectal Cancer Treatments and Studies"
    ]
  ],
  "openalex": "W7172453794",
  "pdf_url": "https://europepmc.org/articles/PMC13719852?pdf=render",
  "pmcid": "PMC13719852",
  "pmid": "42957888",
  "published": "2026-08-04",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/9n2fkprphy7ny.ris",
  "sources": [
    {
      "first_seen": "2026-11-01T00:20:47Z",
      "native_id": "MED:42957888",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42957888"
    },
    {
      "first_seen": "2026-11-02T12:23:44Z",
      "native_id": "PMC13719852",
      "source": "pmc",
      "url": "https://doi.org/10.1007/s00384-026-05210-x"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2730|Colorectal Cancer Treatments and Studies",
      "subfield": "oncology"
    }
  ],
  "title": "Proteinuria with extended VEGF inhibitor therapy in RAS-mutant metastatic colorectal cancer: incidence, interruptions, and exploratory survival analysis.",
  "title_text": "Proteinuria with extended VEGF inhibitor therapy in RAS-mutant metastatic colorectal cancer: incidence, interruptions, and exploratory survival analysis.",
  "type": "peer-reviewed",
  "updated_at": "2026-11-03T12:20:50Z",
  "url": "https://research.draconitic.com/paper/9n2fkprphy7ny",
  "venue": "International journal of colorectal disease",
  "versions": []
}