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

作者：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

来源：International Journal of Gynecological Cancer, 2015, 25(3): 484-492.

DOI：10.1097/IGC.0000000000000380

• Veliparib
• Topotecan
• Cervical cancer
• Poly (ADP-ribose) polymerase

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/m(2)) 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.

• 出版日期2015-3