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01-02-2010 | Original Article

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

Authors: Anda M. Vlad, Raluca A. Budiu, Diana E. Lenzner, Yun Wang, Julia A. Thaller, Kelly Colonello, Peggy A. Crowley-Nowick, Joseph L. Kelley, Fredric V. Price, Robert P. Edwards

Published in: Cancer Immunology, Immunotherapy | Issue 2/2010

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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Title: A phase II trial of intraperitoneal interleukin-2 in patients with platinum-resistant or platinum-refractory ovarian cancer
Authors: Anda M. Vlad
Raluca A. Budiu
Diana E. Lenzner
Yun Wang
Julia A. Thaller
Kelly Colonello
Peggy A. Crowley-Nowick
Joseph L. Kelley
Fredric V. Price
Robert P. Edwards
Publication date: 01-02-2010
Publisher: Springer-Verlag
Published in: Cancer Immunology, Immunotherapy / Issue 2/2010
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-009-0750-3

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