Pilot trial of bone-targeted therapy with zoledronate, thalidomide, and interferon-γ for metastatic renal cell carcinoma

Authors

  • Nizar Tannir MD,

    1. Department of Genitourinary Medical Oncology, University of Texas M. D. Anderson Cancer Center, Houston, Texas
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    • Dr. Tannir has a family member who owns stock worth less than $100,000 in Novartis.

  • Eric Jonasch MD,

    1. Department of Genitourinary Medical Oncology, University of Texas M. D. Anderson Cancer Center, Houston, Texas
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  • Lance C. Pagliaro MD,

    1. Department of Genitourinary Medical Oncology, University of Texas M. D. Anderson Cancer Center, Houston, Texas
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  • Paul Mathew MD,

    1. Department of Genitourinary Medical Oncology, University of Texas M. D. Anderson Cancer Center, Houston, Texas
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  • Arlene Siefker-Radtke MD,

    1. Department of Genitourinary Medical Oncology, University of Texas M. D. Anderson Cancer Center, Houston, Texas
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  • Laurence Rhines MD,

    1. Department of Neurosurgery, University of Texas M. D. Anderson Cancer Center, Houston, Texas
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  • Patrick Lin MD,

    1. Department of Orthopedic Surgery, University of Texas M. D. Anderson Cancer Center, Houston, Texas
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  • Rita Tibbs MD,

    1. Department of Pathology, University of Texas M. D. Anderson Cancer Center, Houston, Texas
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  • Kim-Anh Do PhD,

    1. Department of Biostatistics and Applied Math, University of Texas M. D. Anderson Cancer Center, Houston, Texas
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  • Sue-Hwa Lin PhD,

    1. Department of Genitourinary Medical Oncology, University of Texas M. D. Anderson Cancer Center, Houston, Texas
    2. Department of Molecular Pathology, University of Texas M. D. Anderson Cancer Center, Houston, Texas
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  • Shi-Ming Tu MD

    Corresponding author
    1. Department of Genitourinary Medical Oncology, University of Texas M. D. Anderson Cancer Center, Houston, Texas
    • Department of Genitourinary Medical Oncology, Unit 1374, University of Texas M. D. Anderson Cancer Center, 1155 Herman Pressler, PO Box 304139, Houston, TX 77230
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    • Fax: (713) 745-1625


Abstract

BACKGROUND.

The purpose of the study was to evaluate the efficacy and safety of a bone-targeted regimen consisting of zoledronate, thalidomide, and interferon-γ in patients with renal cell carcinoma and bone metastases.

METHODS.

Eligible patients had radiographic evidence of bone metastasis. Impending pathologic fractures or spinal cord compressions must have been controlled by surgery or radiation therapy before enrollment. Zoledronate (4 mg) was given intravenously every 4 weeks, thalidomide (300 mg) was given orally once a day, and interferon-γ (100 μg) was given subcutaneously once a week. Patients were evaluated for time to skeletal-related events, the appearance of calcification in osteolytic metastases, and levels of the bone formation/resorption markers.

RESULTS.

Fifteen patients were treated between November 2002 and November 2003; 12 had previously undergone surgery, radiation, or embolization for their bone metastases; 11 had more than 3 sites of bone involvement; and 9 also had nonosseous metastases in the lung, liver, lymph node, pancreas, or adrenal gland. The median time to progression was 8.3 weeks (range, 2.1–48 weeks). The median time to a skeletal-related event was 12.0 weeks (range, 3.9–46.4 weeks). Two patients discontinued treatment because of adverse drug reactions (1 deep venous thrombosis and 1 myocardial infarction). Two patients experienced pain improvement and developed calcification in osseous metastases; these patients also showed favorable changes in bone marker levels.

CONCLUSIONS.

In this pilot study a bone-targeted regimen combining zoledronate, thalidomide, and interferon-γ was well tolerated and might provide clinical benefit for a small subset of patients with renal cell carcinoma and bone metastases. Cancer 2006. © 2006 American Cancer Society.

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