TY - JOUR T1 - 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: An NRG Oncology/Gynecologic Oncology Group Study JF - International Journal of Gynecologic Cancer JO - Int J Gynecol Cancer SP - 484 LP - 492 DO - 10.1097/IGC.0000000000000380 VL - 25 IS - 3 AU - Charles Kunos AU - Wei Deng AU - Dawn Dawson AU - Jayanthi S. Lea AU - Kristine M. Zanotti AU - Heidi J. Gray AU - David P. Bender AU - Perry P. Guaglianone AU - Jori S. Carter AU - Kathleen N. Moore Y1 - 2015/03/01 UR - http://ijgc.bmj.com/content/25/3/484.abstract N2 - Purpose 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.Experimental Design This phase I-II trial examined twice-daily oral veliparib (10 mg) given during once-daily intravenous topotecan (0.6 mg/m2) 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.Results 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; P = 0.02) and survival (hazard ratio, 0.12; P = 0.005) after veliparib-topotecan therapy.Conclusions 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. ER -