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)

作者：Owonikoko Taofeek K^*; Dahlberg Suzanne E; Khan Saad A; Gerber David E; Dowell Jonathan; Moss Rebecca A; Belani Chandra P; Hann Christine L; Aggarwal Charu; Ramalingam Suresh S

来源：Lung Cancer, 2015, 89(1): 66-70.

DOI：10.1016/j.lungcan.2015.04.015

• Small cell
• Veliparib
• PARP
• Phase I

Objectives: 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.
Materials and 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 (100 mg/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 100 mg (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-naive, 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 100 mg dose (DLT in 1 of 6 patients; grade 5 cardiac failure). Veliparib at 100 mg 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.

• 出版日期2015-7