aflibercept + capecitabine + oxaliplatin

This combination is being studied as a treatment regimen for metastatic colorectal cancer. The combination is also known as XELOX (capecitabine/oxaliplatin) with ziv-aflibercept. ## Drug Components and Mechanism The combination consists of three distinct agents: 1. **Ziv-aflibercept**: A recombinant fusion protein containing portions of VEGFR1 and VEGFR2 extracellular domains. It binds to VEGF-A, VEGF-B, and placental growth factor (PlGF), inhibiting VEGF-mediated angiogenesis[6][8]. 2. **Capecitabine**: An oral fluoropyrimidine carbamate that functions as a prodrug, converting to 5-fluorouracil in tumor tissue. It's considered interchangeable with intravenous 5-FU based on similar efficacy and safety profiles[9]. 3. **Oxaliplatin**: A platinum-based chemotherapy agent that causes DNA damage through DNA crosslinking, particularly intrastrand and interstrand crosslinking. Its diamino cyclohexane (DACH) structure prevents cross-resistance with other platinum compounds like cisplatin and carboplatin[7]. ## Clinical Development A Phase II clinical trial (NCT02079220) has been conducted to evaluate the anti-tumor activity, safety, and tolerability of ziv-aflibercept in combination with XELOX chemotherapy in the first-line treatment of patients with metastatic colorectal cancer[1][10]. The trial investigated two different dosing schedules: - **Arm A (every 2 week schedule)**: - Capecitabine: 1,000 mg/m² orally twice daily on Days 1-7, repeating every 14 days - Oxaliplatin: 85 mg/m² IV on Day 1, repeating every 14 days - Ziv-aflibercept: 4 mg/kg IV on Day 1, repeating every 14 days - **Arm B (every 3 week schedule)**: - Capecitabine: 850 mg/m² orally twice daily on Days 1-14, repeating every 21 days - Oxaliplatin: 130 mg/m² IV on Day 1, repeating every 21 days - Ziv-aflibercept: 6 mg/kg IV on Day 1, repeating every 21 days[1] While ziv-aflibercept is FDA-approved in combination with FOLFIRI (5-fluorouracil, leucovorin, and irinotecan) for second-line treatment of metastatic colorectal cancer, its combination with XELOX represents an investigational approach[4][6]. Another study demonstrated that the combination of capecitabine and ziv-aflibercept showed acceptable safety and tolerability, with progression-free survival at 2 months significantly greater than historical controls in patients with chemotherapy-refractory metastatic colorectal cancer[9]. This combination represents an important area of investigation in the evolving landscape of antiangiogenic therapies for colorectal cancer, alongside other agents like bevacizumab and regorafenib.

Other names

XELOX (capecitabine/oxaliplatin) with ziv-aflibercept