TY - JOUR
T1 - A phase i trial of pegylated liposomal doxorubicin (PLD), carboplatin, bevacizumab and veliparib in recurrent, platinum-sensitive ovarian, primary peritoneal, and fallopian tube cancer
T2 - An NRG Oncology/Gynecologic Oncology Group study
AU - Landrum, Lisa M.
AU - Brady, William E.
AU - Armstrong, Deborah K.
AU - Moore, Kathleen N.
AU - Disilvestro, Paul A.
AU - O'Malley, David M.
AU - Tenney, Meaghan E.
AU - Rose, Peter G.
AU - Fracasso, Paula M.
N1 - Publisher Copyright:
© 2015 Elsevier Inc.
PY - 2016
Y1 - 2016
N2 - Objective To determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs) of veliparib combined with PLD and carboplatin (CD) in patients with recurrent, platinum-sensitive epithelial ovarian cancer. To determine the tolerability at the MTD combined with bevacizumab. Methods Patients received PLD (30 mg/m2, IV) and carboplatin (AUC 5, IV) on day 1 with veliparib on days 1-7 (intermittent) or days 1-28 (continuous). Standard 3 + 3 design was used in the dose escalation phase with DLTs based on the first cycle. Once the MTDs were determined, cohorts of 6 patients were enrolled to each regimen with bevacizumab (10 mg/kg on days 1 and 15) to assess feasibility. DLTs were based on the first 4 cycles of treatment in the bevacizumab cohorts. Results In the dose-escalation phase, 27 patients were treated at 3 dose levels with DLTs noted in 6 patients including grade 4 thrombocytopenia (n = 4), and prolonged neutropenia > 7 days (n = 3). At the MTD of veliparib (80 mg p.o. b.i.d. for both dosing arms), myelosuppression was the DLT. At MTD, 12 additional patients were treated with bevacizumab with 9 patients experiencing DLTs including grade 4 thrombocytopenia (n = 4), prolonged neutropenia > 7 days (n = 1), grade 3 hypertension (n = 5), and grade 5 sepsis (n = 1). Conclusions The MTD of veliparib combined with CD is 80 mg p.o. b.i.d. in women with recurrent, platinum-sensitive ovarian cancer. With bevacizumab, DLTs were noted in 9 out of 12 patients. Lower doses of veliparib will need to be considered when given in combination with platinum-based therapies.
AB - Objective To determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs) of veliparib combined with PLD and carboplatin (CD) in patients with recurrent, platinum-sensitive epithelial ovarian cancer. To determine the tolerability at the MTD combined with bevacizumab. Methods Patients received PLD (30 mg/m2, IV) and carboplatin (AUC 5, IV) on day 1 with veliparib on days 1-7 (intermittent) or days 1-28 (continuous). Standard 3 + 3 design was used in the dose escalation phase with DLTs based on the first cycle. Once the MTDs were determined, cohorts of 6 patients were enrolled to each regimen with bevacizumab (10 mg/kg on days 1 and 15) to assess feasibility. DLTs were based on the first 4 cycles of treatment in the bevacizumab cohorts. Results In the dose-escalation phase, 27 patients were treated at 3 dose levels with DLTs noted in 6 patients including grade 4 thrombocytopenia (n = 4), and prolonged neutropenia > 7 days (n = 3). At the MTD of veliparib (80 mg p.o. b.i.d. for both dosing arms), myelosuppression was the DLT. At MTD, 12 additional patients were treated with bevacizumab with 9 patients experiencing DLTs including grade 4 thrombocytopenia (n = 4), prolonged neutropenia > 7 days (n = 1), grade 3 hypertension (n = 5), and grade 5 sepsis (n = 1). Conclusions The MTD of veliparib combined with CD is 80 mg p.o. b.i.d. in women with recurrent, platinum-sensitive ovarian cancer. With bevacizumab, DLTs were noted in 9 out of 12 patients. Lower doses of veliparib will need to be considered when given in combination with platinum-based therapies.
KW - PARP inhibitors
KW - Thrombocytopenia
KW - VEGF inhibitors
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U2 - 10.1016/j.ygyno.2015.11.024
DO - 10.1016/j.ygyno.2015.11.024
M3 - Article
C2 - 26616225
AN - SCOPUS:84961155071
SN - 0090-8258
VL - 140
SP - 204
EP - 209
JO - Gynecologic oncology
JF - Gynecologic oncology
IS - 2
ER -