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Phase I trial of PEG-interferon and recombinant IL-2 in patients with metastatic renal cell carcinoma

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Abstract

Purpose

Pegylated interferon α-2b (PEG-Intron®) is a conjugate of polyethylene glycol (PEG) and interferon alpha-2b, has a prolonged half-life, and an increased area under the curve (AUC) for interferon α-2b. The combination of PEG-Intron® with recombinant interleukin-2 (rIL-2) was investigated in a phase 1 trial. To determine the maximal tolerable dose (MTD) and preliminary efficacy of concurrent subcutaneous (SC) administration of PEG-Intron® and rIL-2 in patients with metastatic renal cell carcinoma (RCC).

Methods

Cohorts of 3–6 patients received escalating doses of PEG-Intron® (I-1.5, II- 1.5, III-3.0, IV-3.0, V-4.5 μg/kg SC) given weekly in combination with rIL-2 administered three times weekly (TIW) for 6 weeks. rIL-2 dose levels were escalated in weeks 1 and 4 (I-10.0, II-15.0, III-15.0, IV-20.0, V-20.0 MIU/m2 SC), and 5.0 MIU/m2 SC TIW was administered during weeks 2, 3, 5 and 6.

Results

Thirty-four patients (24 men; 10 women) were accrued at dose levels I (n = 4), II (n = 4), III (n = 6), IV (n = 14), and V (n = 6) between October 2000 and October 2002. All but one patient had prior nephrectomy (n = 33) and all but one patient (97%) had received no prior systemic therapy. Patients received a median of four cycles of treatment (range 1–9). Dose limiting toxicity occurred at dose level V and included grade 4 neutropenia and hypoxemia. A partial response was found in 5 pts (15%). Median progression-free and overall survival were 9.0 (95% C.I. 5.6–13.1 months) and 31.9 months (95% C.I. 17.2–61.9 months), respectively.

Conclusion

The combination of PEG-Interferon and SC rIL-2 can be administered with acceptable toxicity.

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Acknowledgement

We thank the Nursing Staff of the Experimental Therapeutics Program of the Cleveland Clinic Taussig Cancer Center.

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Authors and Affiliations

  1. Experimental Therapeutics Program, Department of Hematology and Medical Oncology/ R33, The Cleveland Clinic Taussig Cancer Center, 9500 Euclid Ave, Cleveland, OH, 44195, USA

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

  2. Department of Immunology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH, 44195, USA

    James Finke & Ronald M. Bukowski

  3. GU Oncology Program, Baylor Sammons Cancer Center, Dallas, TX, USA

    Thomas E. Hutson

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  1. Saby George
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  2. Thomas E. Hutson
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  3. Tarek Mekhail
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  8. Ronald M. Bukowski
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Correspondence to Ronald M. Bukowski.

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Supported by a grant from Schering-Plough Inc. and the Zito Chair for Cancer Research and the Rudy Fund for Cancer Research.

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George, S., Hutson, T.E., Mekhail, T. et al. Phase I trial of PEG-interferon and recombinant IL-2 in patients with metastatic renal cell carcinoma. Cancer Chemother Pharmacol 62, 347–354 (2008). https://doi.org/10.1007/s00280-007-0594-5

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  • DOI: https://doi.org/10.1007/s00280-007-0594-5

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