Phase I study of intravenous (IV) XXXX and intraperitoneal (IP) @entity901 in recurrent ovarian and fallopian tube cancer.

@entity901 @entity1 @entity137 @entity168 @entity6887 @entity10190 @entity1398 @entity601 @entity490 @entity1205
OBJECTIVE: The primary objective was to define the maximum tolerated dose (MTD) and dose-limiting @entity137 (DLT) of IV @entity1205 and IP @entity901 in @entity1 with recurrent ovarian (OV), @entity6887 . Secondary objectives included response rate, time to progression, pharmacokinetics (PK) and quality of life (QoL). METHODS: @entity1 received @entity1205 75mg/m(2) IV day (d) 1 and @entity901 escalating from 50mg/m(2) @entity10190 every 3weeks using a 3+3 design. Treatment continued until disease progression, remission, or intolerable @entity137 . Plasma and IP samples were taken to determine drug concentrations. @entity601 Anderson Symptom Inventory and symptom interference scale were completed weekly. RESULTS: Thirteen @entity1 were included. Median number of cycles was 6 (range 1-10). Ten @entity1 had measureable disease. Best response was partial response (PR-2), stable disease ( @entity168 -7), and progressive disease (PD-1). Twenty-one Grades 3-4 @entity137 were noted, commonly hematologic. Two @entity1 had DLTs: prolonged @entity1398 (1) and @entity490 (1). MTD was d1 @entity1205 75mg/m(2) IV and d2 @entity901 50mg/m(2) IP. Symptom burden peaked week one and returned to baseline by week two of each cycle on dose level 1. Dose level 2 had persistently high symptom burden and interference. At IP @entity901 doses of 50mg/m(2), total unbound drug exposure (AUC) averaged 8 times larger and Cmax reached concentrations 50-fold greater in IP fluid compared to plasma. CONCLUSIONS: @entity1205 75mg/m(2) IV d1 and @entity901 50mg/m(2) @entity10190 is the MTD. Most @entity1 had PR or @entity168 . @entity1 -reported outcomes demonstrate temporary but tolerable decrements in QoL. IP @entity901 provides PK advantages over IV administration.
