Skip to content
DraconiticResearch
Search Sources API
181,716 studies31 sourcesUpdated 38 min ago
Peer-reviewedCC BYInternational journal of colorectal disease

Proteinuria with extended VEGF inhibitor therapy in RAS-mutant metastatic colorectal cancer: incidence, interruptions, and exploratory survival analysis.

  • Daichi Watanabe1,2
  • Hironori Fujii3
  • Yuto Miura4
  • Misato Kani4
  • Wakana Chikaishi5
  • Jesse Yu Tajima5
  • Akitaka Makiyama6
  • Yunami Yamada1
  • Koichi Ohata1
  • Chiemi Hirose1
  • Hirotoshi Iihara1,7,8
  • Ryo Kobayashi1,4
2 more authors
  • Nobuhisa Matsuhashi5
  • Akio Suzuki1,4
8 affiliations
  1. 1Department of Pharmacy, Gifu University Hospital, Gifu, Japan.
  2. 2Innovative and Clinical Research Promotion Center, Gifu University Hospital, Gifu, Japan.
  3. 3Department of Pharmacy, Gifu University Hospital, Gifu, Japan. [email protected].
  4. 4Laboratory of Advanced Medical Pharmacy, Gifu Pharmaceutical University, Gifu, Japan.
  5. 5Department of Surgical Oncology, Gifu University Graduate School of Medicine, Gifu, Japan.
  6. 6Cancer Center, Gifu University Hospital, Gifu, Japan.
  7. 7Patient Safety Division, Gifu University Hospital, Gifu, Japan.
  8. 8Laboratory of Pharmacy Practice and Social Science, Gifu Pharmaceutical University, Gifu, Japan.
Read full textPDFDOICite

Abstract

Purpose

Vascular 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

This 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

Among 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

Proteinuria 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.

Related

  1. Proteinuria as the cause of early dose modification in Japanese patients with metastatic colorectal cancer treated with fruquintinib: a multicenter real-world study
    Shohei Udagawa, Chihiro Ishizuka, Hiroki Osumi +15
    International Journal of Clinical OncologyPeer-reviewedCC BY 4.0Full textOncologyPMC
  2. Targeting Ion Channel Dysregulation in Colorectal Cancer: Identification of Clofilium as a Potent Inhibitor of Tumor Growth and Metastatic Potential
    Juanita Mathews, Sydney A. Palmer, Sammy Hansali +7
    OSF PreprintsPreprintCC BY 4.0Full textGeneral biologyPhysiologyOSF
  3. Efficacy and safety of cetuximab-irinotecan rechallenge versus regorafenib in ras wild-type metastatic colorectal cancer: a single-center exploratory randomized trial
    Hao Chen, Tao Jiang, Han Wang +9
    BMC CancerPeer-reviewedCC BYFull textOncologyDOAJ
  4. Short-term superiority in proteinuria control with exploratory longitudinal trajectories: finerenone-dapagliflozin combination in non-diabetic kidney disease
    Mali Zhu, Yingyi Deng, Lijun Su +3
    Frontiers in PharmacologyPeer-reviewedCC BY 4.0Full textPharmacology & toxicologyCrossrefEurope PMCPMC
  5. The conformation-selective PI3Kδ inhibitor roginolisib in patients with advanced or metastatic cancer, including metastatic uveal melanoma: first-in-human clinical trial
    Anna Maria Di Giacomo, Matteo Simonelli, Agnese Losurdo +37
    Nature CommunicationsPeer-reviewedCC BY-NC-ND 4.0Full text3 citedGeneral medicineCrossref

Cite

BibTeXRIS
BibTeX
@article{watanabe2026proteinuria,
  title = {{Proteinuria with extended VEGF inhibitor therapy in RAS-mutant metastatic colorectal cancer: incidence, interruptions, and exploratory survival analysis.}},
  author = {Daichi Watanabe and Hironori Fujii and Yuto Miura and Misato Kani and Wakana Chikaishi and Jesse Yu Tajima and Akitaka Makiyama and Yunami Yamada and Koichi Ohata and Chiemi Hirose and Hirotoshi Iihara and Ryo Kobayashi and Nobuhisa Matsuhashi and Akio Suzuki},
  journal = {International journal of colorectal disease},
  year = {2026},
  month = aug,
  doi = {10.1007/s00384-026-05210-x},
  url = {https://europepmc.org/article/MED/42957888},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Proteinuria with extended VEGF inhibitor therapy in RAS-mutant metastatic colorectal cancer: incidence, interruptions, and exploratory survival analysis.
AU  - Daichi Watanabe
AU  - Hironori Fujii
AU  - Yuto Miura
AU  - Misato Kani
AU  - Wakana Chikaishi
AU  - Jesse Yu Tajima
AU  - Akitaka Makiyama
AU  - Yunami Yamada
AU  - Koichi Ohata
AU  - Chiemi Hirose
AU  - Hirotoshi Iihara
AU  - Ryo Kobayashi
AU  - Nobuhisa Matsuhashi
AU  - Akio Suzuki
PY  - 2026
DA  - 2026/08/04
JO  - International journal of colorectal disease
DO  - 10.1007/s00384-026-05210-x
UR  - https://europepmc.org/article/MED/42957888
AB  - Purpose  Vascular 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  This 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  Among 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  Proteinuria 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.
SN  - 0179-1958
SN  - 1432-1262
ER  -