1. Identifying the need to refine the potential patient risk factors for niraparib-induced thrombocytopenia
- Author
-
Elizabeth K Nugent, Tran N. Le, Chenchen H. Sun, Grace Martin, Joseph A. Lucci, Judith A. Smith, and Anjali Gaikwad
- Subjects
Blood Platelets ,0301 basic medicine ,medicine.medical_specialty ,Indazoles ,Patient risk ,Renal function ,Poly(ADP-ribose) Polymerase Inhibitors ,Gastroenterology ,03 medical and health sciences ,0302 clinical medicine ,Piperidines ,Maintenance therapy ,Risk Factors ,Internal medicine ,Humans ,Medicine ,Platelet ,Hypoalbuminemia ,Dosing ,Aged ,Ovarian Neoplasms ,business.industry ,Obstetrics and Gynecology ,Middle Aged ,medicine.disease ,Thrombocytopenia ,030104 developmental biology ,Oncology ,030220 oncology & carcinogenesis ,Toxicity ,Female ,business ,Ovarian cancer - Abstract
Objective Niraparib is a poly (ADP-ribose) polymerase inhibitor (PARP) approved for use in maintenance therapy for ovarian cancer that is associated with the unpredictable grade 3/4 thrombocytopenia. This study was conducted to refine patient dosing recommendations for niraparib based upon clinical practice observations of grade 3/4 thrombocytopenia. Methods and materials Six patient cases were reviewed to identify similarities in patient factors. An in vitro study was conducted using healthy volunteer blood spiked with Niraparib concentrations ranging from 0 ng/mL to 5000 ng/mL. Manual platelet counts were evaluated at different time intervals for each concentration and compared to untreated controls. Data was then analyzed based on percent change in platelet count versus untreated control for each concentration/time point. Results In three patients with body weight > 80 kg and platelet count >200 × 109/L, decreased creatinine clearance (CrCl) Conclusion The data suggests that renal insufficiency and hypoalbuminemia may be associated with the development of niraparib-induced thrombocytopenia. Moreover, the preliminary in vitro studies also demonstrated a concentration-dependent relationship between niraparib and direct toxicity to platelets.
- Published
- 2019