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ABSTRACT: Objective
We assessed the safety and maximum tolerated dose (MTD) of the poly ADP-ribose polymerase (PARP) inhibitor olaparib with intravenous (IV)/intraperitoneal (IP) cisplatin/paclitaxel and IV bevacizumab, followed by olaparib and bevacizumab maintenance, in patients with newly diagnosed ovarian cancer who had undergone primary debulking surgery.Methods
Treatment included: (Cycles 1-6) Day 1, IV paclitaxel 135 mg/m2/3 h + (from Cycle 2 onward) bevacizumab 15 mg/kg; Day 2, IP cisplatin 75 mg/m2; Days 2-8, olaparib (50/100/200 mg BID); Day 8, IP paclitaxel 60 mg/m2 of a 21-day cycle. Maintenance (Cycles 7-22) included: olaparib 300 mg BID and bevacizumab 15 mg/kg Day 1. The primary endpoint was MTD of olaparib, chemotherapy, and bevacizumab.Results
Seventeen women were treated (Cohort 1 [50 mg olaparib], 8 patients; Cohort 2 [100 mg], 3 patients; and Cohort 3 [200 mg], 6 patients). Median age was 57 years (47-73); 94% had stage III disease; 29% had a germline BRCA mutation. Two of 6 patients in Cohort 3 experienced a dose-limiting toxicity (DLT). Grade 3/4 toxicities included: neutropenia (56%), lymphopenia (31%), anemia (25%), and fatigue (19%). Most patients started (88%, 81%) and completed (75%, 50%) maintenance olaparib and bevacizumab, respectively; 36% of patients on olaparib maintenance required a dose reduction. Median PFS was 33 months (26.2-NA).Conclusions
The MTD of intermittently dosed olaparib with concurrent IV/IP cisplatin/paclitaxel and bevacizumab is 100 mg BID. Non-hematologic toxicities were predominantly low grade. One-third of patients on olaparib maintenance required dose reduction.
SUBMITTER: Cadoo KA
PROVIDER: S-EPMC7127949 | biostudies-literature | 2020 Apr
REPOSITORIES: biostudies-literature
Cadoo Karen A KA Grisham Rachel N RN O'Cearbhaill Roisin E RE Boucicaut Nicole N NN Henson Melissa M Iasonos Alexia A Zhou Qin Q Sarasohn Debra M DM Gallagher Jacqueline J Kravetz Sara S Zamarin Dmitriy D Makker Vicky V Sabbatini Paul J PJ Tew William P WP Aghajanian Carol C Konner Jason A JA
Gynecologic oncology 20200117 1
<h4>Objective</h4>We assessed the safety and maximum tolerated dose (MTD) of the poly ADP-ribose polymerase (PARP) inhibitor olaparib with intravenous (IV)/intraperitoneal (IP) cisplatin/paclitaxel and IV bevacizumab, followed by olaparib and bevacizumab maintenance, in patients with newly diagnosed ovarian cancer who had undergone primary debulking surgery.<h4>Methods</h4>Treatment included: (Cycles 1-6) Day 1, IV paclitaxel 135 mg/m<sup>2</sup>/3 h + (from Cycle 2 onward) bevacizumab 15 mg/kg; ...[more]