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Abstract
Introduction. Metastatic colorectal cancer (mCRC) continues to demonstrate persistently high incidence and mortality rates. There remains an unmet need to reduce treatment-related complications and improve quality of life in mCRC patients receiving the mFOLFOX-6 + bevacizumab treatment. Emerging evidence suggests extracellular vesicles (EVs) play a significant role in colorectal carcinogenesis, with elevated levels observed in mCRC patients. These findings suggest potential utility for EVs - both as therapeutic targets through plasmapheresis-mediated reduction and as predictive biomarkers.
Aim. To evaluate the clinical efficacy and safety profile of combining plasmapheresis with first-line mFOLFOX-6/bevacizumab therapy in mCRC patients, with particular focus on EV levels.
Materials and Methods. This prospective, open-label, single-center study was conducted from June 2020 to April 2023 and included 58 patients with metastatic colorectal cancer (mCRC). Patients were divided into two groups: the experimental group (n = 28) received plasmapheresis combined with mFOLFOX-6/bevacizumab, while the control group (n = 30) received mFOLFOX-6/bevacizumab alone. Endpoints included objective response rate (ORR, RECIST 1.1), progression-free survival (PFS), and overall survival (OS), treatment toxicity (CTCAE v5.0), quality of life (EORTC QLQ-C30), and plasma EVs levels.
Results. Efficacy outcomes were comparable between groups: ORR: 39% (experimental) vs. 30% (control), p > 0.05; PFS: 10.7 vs. 10.0 months, p = 0.51; OS: 28.4 months (experimental) vs. median not reached (control), p = 0.43. The experimental group demonstrated significantly reduced complications: anemia (G1–2): 29% vs. 67%, p = 0.005; thrombocytopenia (G1–2): 4% vs. 27%, p = 0.005; hypertension (G1–2): 7% vs. 30%. Emotional functioning improved in the plasmapheresis group (p = 0.013), whereas the control group showed worsened physical functioning (p = 0.005) and increased fatigue (p < 0.001). A threshold EV level of 2.0 × 10¹¹ particles/mL was identified, above which tumor progression (> 0% growth) was observed (AUC 0.938, 95% CI 0.762–1.0, p = 0.043).
Conclusion. The addition of plasmapheresis to mFOLFOX-6/bevacizumab did not enhance antitumor efficacy but significantly reduced toxicity and improved quality of life in mCRC patients. EV levels post-plasmapheresis showed predictive potential for tumor growth, warranting further investigation.
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