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Figure S1 from A Phase I Clinical, Pharmacokinetic, and Pharmacodynamic Study of Weekly or Every Three Week Ixabepilone and Daily Sunitinib in Patients with Advanced Solid Tumors

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posted on 2023-03-31, 18:23 authored by Alberto J. Montero, Deukwoo Kwon, Aurea Flores, Krisztina Kovacs, Jonathan C. Trent, Pasquale Benedetto, Caio Rocha-Lima, Jaime R. Merchan

Figure S1. Correlative Angiogenesis Biomarkers. A, levels of circulating endothelial cells in patients in schedule A and B at baseline (Pre-treatment). B, circulating endothelial precursor cells (EPCs) at baseline in patients in schedule A and B. C, baseline plasma angiogenic activity (PAA) at baseline in patients in schedule A and B.

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ARTICLE ABSTRACT

Purpose: To evaluate the safety, MTD, pharmacokinetics/pharmacodynamics, and early clinical activity of ixabepilone given either weekly or every 3 weeks in combination with daily sunitinib in patients with advanced solid tumors.Experimental Design: Eligible patients received either weekly (schedule A) or every 3 weeks (schedule B) ixabepilone at escalating doses (schedule A: 7.5, 15, or 20 mg/m2; schedule B: 20, 30, or 40 mg/m2), and oral sunitinib (37.5 mg daily), starting on day 8 of cycle 1. Dose-limiting toxicities (DLT) were assessed during cycle 1.Results: The ixabepilone and sunitinib combination was fairly well tolerated. DLTs were observed in 3 subjects (1 in schedule 3A and 2 in schedule 3B). The most common grade 3–4 hematologic and nonhematologic adverse events were leukopenia and fatigue, respectively. Four patients (3 in schedule A) achieved a partial response, while 13 patients had stable disease. Nine of 17 heavily pretreated colorectal cancer patients had clinical benefit. Coadministration of sunitinib with ixabepilone on a weekly (but not every 3 week) schedule was associated with a significant increase in the half-life and a significant decrease in the clearance of ixabepilone. Correlative studies demonstrated a significant association between higher baseline plasma angiogenic activity (PAA) and clinical benefit in schedule A patients. Weekly, but not every 3 weeks, ixabepilone led to a significant decrease in PAA postbaseline.Conclusions: Coadministration of ixabepilone with sunitinib has acceptable toxicity and encouraging clinical activity in heavily pretreated patients, particularly in patients with metastatic colorectal cancer. Clin Cancer Res; 22(13); 3209–17. ©2016 AACR.

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