A Phase I-II Evaluation of Veliparib (NSC #737664), Topotecan, and Filgrastim or Pegfilgrastim in the Treatment of Persistent or Recurrent Carcinoma of the Uterine Cervix. Issue 3 (March 2015)

• Record Type: Journal Article
• Authors: Kunos, Charles; Deng, Wei; Dawson, Dawn; Lea, Jayanthi S.; Zanotti, Kristine M.; Gray, Heidi J.; Bender, David P.; Guaglianone, Perry P.; Carter, Jori S.; Moore, Kathleen N.
• Is Part Of: International journal of gynecological cancer. Volume 25:Issue 3(2015:Mar.)
• Publication Date: 2015-03
• Subjects: Generative organs, Female -- Cancer -- Periodicals; 616.99465
• DOI: 10.1097/IGC.0000000000000380
• Languages: English
• ISSNs: 1048-891X

Abstract

<abstract> <title> <x xml:space="preserve">Abstract</x> </title> <sec> <title>Purpose</title> <p>The aim of this study was to evaluate the tolerability and efficacy of poly(ADP-ribose) polymerase (PARP) inhibition by veliparib during cytotoxic topotecan administration with filgrastim or pegfilgrastim neutrophil support in women with persistent or recurrent uterine cervix cancer.</p> </sec> <sec> <title>Experimental Design</title> <p>This phase I-II trial examined twice-daily oral veliparib (10 mg) given during once-daily intravenous topotecan (0.6 mg/m<sup>2</sup>) on days 1 to 5 of each treatment cycle. Cycles were repeated every 21 days until disease progression or until toxicity prohibited further therapy. Toxicity and objective response rate were primary endpoints.</p> </sec> <sec> <title>Results</title> <p>Twenty-seven women were enrolled. Frequently reported grade 3 or higher treatment-related toxicities were anemia (59%), thrombocytopenia (44%), leukopenia (22%), and neutropenia (19%). There were 2 partial responses (7% [90% confidence interval, 1%–22%]). Four patients had a disease progression date more than 6 months after the start of veliparib-topotecan therapy. Patients with low immunohistochemical expression (0–1+) of PARP-1 in their primary uterine cervix cancer were more likely to have a longer progression-free interval (hazard ratio, 0.25; <italic>P</italic> = 0.02) and survival (hazard ratio, 0.12; <italic>P</italic> = 0.005) after veliparib-topotecan therapy.</p> </sec> <sec> <title>Conclusions</title> <p>Clinical activity of a veliparib-topotecan combination was minimal in women with persistent or recurrent uterine cervix cancer. Women whose uterine cervix cancers express PARP-1 at low levels may benefit preferentially from PARP inhibitors combined with cytotoxic therapies, suggesting further study of PARP expression as an integral triage biomarker.</p> </sec> </abstract>