A phase II trial of intraperitoneal interleukin-2 in patients  with platinum-resistant or platinum-refractory ovarian cancer.
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 x 10(5) 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.
Vlad
Anda M
AM
Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Pittsburgh School of Medicine, 300 Halket Str, Pittsburgh, PA 15213, USA.
Budiu
Raluca A
RA
Lenzner
Diana E
DE
Wang
Yun
Y
Thaller
Julia A
JA
Colonello
Kelly
K
Crowley-Nowick
Peggy A
PA
Kelley
Joseph L
JL
Price
Fredric V
FV
Edwards
Robert P
RP
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D019008:Drug Resistance, Neoplasm; D004802:Eosinophilia / Q000276:immunology; D005260:Female; D006801:Humans; D007274:Injections, Intraperitoneal; D007376:Interleukin-2 / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008214:Lymphocytes / Q000276:immunology; D008218:Lymphocytosis / Q000276:immunology; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000401:mortality; D017671:Platinum Compounds / Q000627:therapeutic use; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D007376:Interleukin-2; D017671:Platinum Compounds; D011994:Recombinant Proteins
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