title: A phase 1 safety study of veliparib combined with cisplatin and etoposide in extensive stage small cell lung cancer: A trial of the ECOG-ACRIN Cancer Research Group (E2511).
abstract: OBJECTIVE
  Veliparib (V) potentiated therapeutic efficacy of cisplatin (C) and etoposide (E) in preclinical models of SCLC. We conducted this phase 1 study to establish the safety of the combination in human subjects.
  
  
  METHODS
  The study employed the 3+3 dose escalation design to establish the safety and recommended phase 2 dose (RP2D) of V when combined with fixed doses of C (75 mg/m(2) on day 1) and E (100mg/m(2) on days 1-3) in a 21-day cycle. The starting dose of V was 60 mg (bid days 1-7) with plan to escalate to 100mg (days 1-7) or de-escalate to 40 mg (days 1-7) depending on the dose limiting toxicity (DLT) experience during cycle 1. Patients with treatment-naïve, extensive stage SCLC were included.
  
  
  RESULTS
  The study enrolled 9 patients: M/F (4/5); median age (60); White/African American (8/1). V was tolerated at the 60 mg (DLT in 0 of 3 patients) and 100mg dose (DLT in 1 of 6 patients; grade 5 cardiac failure). Veliparib at 100mg in combination with standard doses of C and E was established as the RP2D. Grades 3-5 adverse events irrespective of attribution during cycle 1 included: dehydration (1), diarrhea (1), fatigue (1), febrile neutropenia (1), heart failure (1), leukopenia (6), lymphopenia (1), nausea (2), neutropenia (8), respiratory failure (1), and thrombocytopenia (2). Investigator-assessed efficacy outcome in 7 evaluable patients were stable disease in 2/7 (28.6%), partial response in 4/7 (57.1%), and complete response in 1/7 (14.3%) patients.
  
  
  CONCLUSIONS
  This study demonstrated the safety of combining veliparib with cisplatin and etoposide in previously untreated SCLC patients.
authors.affiliation: The Winship Cancer Institute of Emory University, Atlanta, GA, United States. Electronic address: towonik@emory.edu.
authors.forename: Taofeek K
authors.initials: TK
authors.lastname: Owonikoko
authors.affiliation: Dana-Farber Cancer Institute, Boston, MA, United States.
authors.forename: Suzanne E
authors.initials: SE
authors.lastname: Dahlberg
authors.affiliation: University of Texas Southwestern Medical Center, Dallas, TX, United States.
authors.forename: Saad A
authors.initials: SA
authors.lastname: Khan
authors.affiliation: University of Texas Southwestern Medical Center, Dallas, TX, United States.
authors.forename: David E
authors.initials: DE
authors.lastname: Gerber
authors.affiliation: University of Texas Southwestern Medical Center, Dallas, TX, United States.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Dowell
authors.affiliation: Rutgers Cancer Institute of New Jersey and Robert Wood Johnson Medical School, Rutgers, The State University of New Jersey, New Brunswick, NJ 08903-2681, United States.
authors.forename: Rebecca A
authors.initials: RA
authors.lastname: Moss
authors.affiliation: Penn State Hershey Cancer Institute, Hershey, PA, United States.
authors.forename: Chandra P
authors.initials: CP
authors.lastname: Belani
authors.affiliation: The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD, United States.
authors.forename: Christine L
authors.initials: CL
authors.lastname: Hann
authors.affiliation: Abramson Cancer Center at the University of Pennsylvania, Philadelphia, PA, United States.
authors.forename: Charu
authors.initials: C
authors.lastname: Aggarwal
authors.affiliation: The Winship Cancer Institute of Emory University, Atlanta, GA, United States.
authors.forename: Suresh S
authors.initials: SS
authors.lastname: Ramalingam
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects*; D001562:Benzimidazoles / Q000008:administration & dosage / Q000009:adverse effects; D064146:Chemotherapy-Induced Febrile Neutropenia / Q000209:etiology; D002945:Cisplatin / Q000008:administration & dosage; D005047:Etoposide / Q000008:administration & dosage; D005221:Fatigue / Q000139:chemically induced; D005260:Female; D006333:Heart Failure / Q000139:chemically induced; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D055752:Small Cell Lung Carcinoma / Q000188:drug therapy* / Q000473:pathology; D013921:Thrombocytopenia / Q000139:chemically induced
chemical_list: D001562:Benzimidazoles; C521013:veliparib; D005047:Etoposide; D002945:Cisplatin
keywords: PARP; Phase I; Small cell; Veliparib