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A phase I surrogate endpoint study of SU6668 in patients with solid tumors

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Abstract

Purpose. To evaluate the biologic effects of SU6668 in patients with solid tumors using comprehensive measures of pharmacokinetics (PK), functional imaging, and tissue correlative studies. Experimental design. Eligible patients with tumors accessible for core needle biopsy were treated with SU6668 at doses of 200 or 400 mg/m2/day. Functional computed tomography (CT) scan and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) were performed at baseline and repeated 4 weeks and 12 weeks after treatment for analysis of tumor angiogenesis. The PK was analyzed using a high-performance liquid chromatography assay. Tumor specimens obtained via core needle biopsy at baseline and 4 weeks later were analyzed for the biologic effects of SU6668. Results. Six of a total of seven patients received treatment for at least 3 months and underwent comprehensive correlative studies, including PK, imaging, and tissue biopsy. Functional CT showed that five of six patients had decreased blood flow in tumors in response to treatment, and DCE-MRI results indicated significant change of area under the signal intensity vs. time curve (AUC) and/or maximum slope (maximum rate of signal intensity change) in two of four patients evaluated with this technique. PK studies showed that the mean apparent oral clearance (Cloral) measured on day 1 was 6.3 ± 2.7 L/hr/m2, yielding a mean AUC of 16.6 ± 4.3 mg/L·hr. By day 22, the Cloral was 40% more than that observed on day 1. Conclusion. It is feasible to evaluate the biologic effects of antiangiogenic agents using comprehensive surrogate measures.

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Authors and Affiliations

  1. Department of Gastrointestinal Medical Oncology, University of Texas, M. D. Anderson Cancer Center, Houston, TX, USA

    Henry Q. Xiong & James L. Abbruzzese

  2. Department of Thoracic/Head & Neck Medical Oncology, University of Texas, M. D. Anderson Cancer Center, Houston, TX, USA

    Roy Herbst

  3. Department of Diagnostic Radiology, University of Texas, M. D. Anderson Cancer Center, Houston, TX, USA

    Silvana C. Faria, Marshall Hicks & Chusilp (Arthur) Charnsangavej

  4. Department of Pharmacy, University of Texas, M. D. Anderson Cancer Center, Houston, TX, USA

    Catherine Scholz & Timothy Madden

  5. Department of Cancer Biology, University of Texas, M. D. Anderson Cancer Center, Houston, TX, USA

    Darren Davis & David McConkey

  6. Department of Imaging Physics, University of Texas, M. D. Anderson Cancer Center, Houston, TX, USA

    Edward F. Jackson

  7. Department of Biostatistics, University of Texas, M. D. Anderson Cancer Center, Houston, TX, USA

    Kenneth Hess

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  1. Henry Q. Xiong
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  2. Roy Herbst
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  3. Silvana C. Faria
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  4. Catherine Scholz
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  5. Darren Davis
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  6. Edward F. Jackson
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  7. Timothy Madden
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  8. David McConkey
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  9. Marshall Hicks
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  10. Kenneth Hess
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  11. Chusilp (Arthur) Charnsangavej
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  12. James L. Abbruzzese
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Xiong, H.Q., Herbst, R., Faria, S.C. et al. A phase I surrogate endpoint study of SU6668 in patients with solid tumors. Invest New Drugs 22, 459–466 (2004). https://doi.org/10.1023/B:DRUG.0000036688.96453.8d

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  • DOI: https://doi.org/10.1023/B:DRUG.0000036688.96453.8d

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