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Phase I trial of thalidomide and Interleukin-2 in patients with metastatic renal cell carcinoma

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Summary

Background: The treatment of advanced renal cell cancer remains unsatisfactory, therefore new combination regimens such as thalidomide and IL-2 are of interest. A phase I trial of SC IL-2 and oral thalidomide was performed to identify the toxicity, maximum tolerated dose (MTD) and preliminary clinical activity of this regimen. Methods: 33 patients with advanced/metastatic RCC were enrolled. An established 8-week outpatient schedule of subcutaneously administered IL-2 in escalating doses, days 1–5, for 6 weeks with a 2 week rest was utilized with daily oral thalidomide. Cohorts of 4–6 patients were treated at 4 dose levels. Results: Toxicity was moderate to severe and related to dose level. All patients developed fever, chills and fatigue. 29/33 patients developed ≤Grade 2 desquamation of hands and feet and/or rash. Dose limiting toxicity (DLT) included Grade 3 neutropenia and pulmonary embolus. The maximum tolerated dose (MTD) of IL-2 and thalidomide was 9.0 MIU/m2 SC days 1–5, weeks 1 to 6 and 100 mg po daily, respectively. A median of 2 cycles of therapy was administered (range 1–9). 2/33 patients responded (1 CR—prior IL-2 therapy, 1 PR—no prior therapy) with an overall response of 6% (95% CI, 1–20%). One minimal response was converted to a surgical CR (remains disease free at 24 + months). Conclusion: Outpatient administration of IL-2 and thalidomide is possible with acceptable toxicity. Further evaluation of this regimen is underway.

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Authors and Affiliations

  1. Division of Hematology/Oncology, Department of Internal Medicine, Ohio State University, Columbus, Ohio, 43210

    Thomas Olencki

  2. Wenatchee Valley Medical Center, 820 N Chelan Ave, Wenatchee, Washington, 98801

    Sareena Malhi

  3. Cleveland Clinic Taussig Cancer Center, Cleveland Clinic Foundation, Cleveland, Ohio, 44195

    Tarek Mekhail, Robert Dreicer, Paul Elson, Laura Wood & Ronald M. Bukowski

  4. Division of Hematology/Oncology, Department of Internal Medicine, Ohio State University, A433A Starling Loving Hall, 320 W 10th Ave, Columbus, Ohio, 43210

    Thomas Olencki

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  1. Thomas Olencki
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  2. Sareena Malhi
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  3. Tarek Mekhail
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  4. Robert Dreicer
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  5. Paul Elson
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  6. Laura Wood
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  7. Ronald M. Bukowski
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Correspondence to Thomas Olencki.

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Olencki, T., Malhi, S., Mekhail, T. et al. Phase I trial of thalidomide and Interleukin-2 in patients with metastatic renal cell carcinoma. Invest New Drugs 24, 321–326 (2006). https://doi.org/10.1007/s10637-005-5211-z

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  • DOI: https://doi.org/10.1007/s10637-005-5211-z

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