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A phase II trial of intraperitoneal interleukin-2 in patients with platinum-resistant or platinum-refractory ovarian cancer

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Abstract

Ovarian cancer patients with persistent (platinum-resistant) or progressive (platinum-refractory) disease respond poorly to second line chemotherapy and have low survival expectancy. New and improved therapeutic approaches are needed and immune biologics are one possibility. Interleukin-2 (IL-2) is a T-cell growth factor believed to be important in anti-tumor immunity. We performed a phase II clinical trial with intraperitoneal (IP) recombinant IL-2 administered in weekly infusions of 6 × 105 IU/m2. Thirty-one subjects were sequentially entered into the study and clinical responses were surgically confirmed in 24 patients. The primary end point of this study was clinical response with immunologic measurements as secondary end points. The IP regimen was generally well tolerated. Of the 24 patients assessed for response, there were 6 (4 complete, 2 partial) responses for an overall response rate of 25.0% [95% confidence interval (CI) of 11–45]. The median survival of the 31 patient cohort was 2.1 years (95% CI of 1.3–4.4), but for the 6 patients with responses the median survival has not been reached (range 24–120+ months). Eosinophil and lymphocyte numbers were continuously monitored during treatment. Peripheral blood eosinophils were markedly increased at the completion of treatment (p < 0.0001) and associated with increased circulating eotaxin (p = 0.03). We also found significant associations between changes in CD3 counts and survival (p = 0.05) and between IFNγ-secreting CD8 T cells at early time points and survival (p = 0.04). This study provides important evidence for IP IL-2 in platinum-resistant ovarian cancer and identifies several immune correlates of survival.

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Acknowledgments

This work was supported by NIH R21 CA74105-02S1, American Cancer Society, Chiron Therapeutics, PA Department of Health and the Magee-Womens Health Foundation.

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Authors and Affiliations

  1. Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Pittsburgh School of Medicine, 300 Halket Str, Pittsburgh, PA, 15213, USA

    Anda M. Vlad, Raluca A. Budiu & Robert P. Edwards

  2. Magee Womens Research Institute, 204 Craft Ave, Pittsburgh, PA, 15213, USA

    Anda M. Vlad, Raluca A. Budiu, Julia A. Thaller & Robert P. Edwards

  3. University of Pittsburgh Cancer Institute, 201 North Craig Str, Pittsburgh, PA, 15213, USA

    Diana E. Lenzner & Yun Wang

  4. Division of Gynecologic Oncology, Magee Womens Hospital, 300 Halket Str, Pittsburgh, PA, 15213, USA

    Kelly Colonello, Peggy A. Crowley-Nowick, Joseph L. Kelley, Fredric V. Price & Robert P. Edwards

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  1. Anda M. Vlad
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Correspondence to Robert P. Edwards.

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Vlad, A.M., Budiu, R.A., Lenzner, D.E. et al. A phase II trial of intraperitoneal interleukin-2 in patients with platinum-resistant or platinum-refractory ovarian cancer. Cancer Immunol Immunother 59, 293–301 (2010). https://doi.org/10.1007/s00262-009-0750-3

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