Abstract CT412: Phase I study of intraveneous docetaxel and intraperitoneal oxaliplatin in recurrent ovarian, fallopian tube and peritoneal cancer
Authors: Taylor Sarah E. , Li Ruosha , Petschauer Jennifer S. , Donovan Heidi , Zamboni William C. , Edwards Robert P. , Zorn Kristen K. 
Published: May 2015

Abstract
Objective
IP chemotherapy improves survival in advanced ovarian cancer but its use has been limited by toxicity with cisplatin-based regimens. The primary objective was to define the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of IV docetaxel and IP oxaliplatin in women with recurrent ovarian, fallopian tube or peritoneal cancer. Secondary objectives included response rate, time to progression, quality of life (QoL) and pharmacokinetics (PK).
Methods
Patients received docetaxel 75 mg/m2 IV on day (d) 1 and oxaliplatin escalating from 50 mg/m2 IP on d2 every 3 weeks using a 3 + 3 design. Response was evaluated every 2 cycles. Treatment continued until disease progression, remission, or intolerable toxicity. Plasma and IP samples were taken up to 72 hours after dosing to determine drug concentrations via inductively coupled plasma mass spectrometry. PK parameters were estimated for each patient with means then calculated for each dose level. Patients completed the Functional Assessment of Cancer Therapy - Ovarian before each treatment and the MD Anderson Symptom Inventory weekly to assess multi-dimensional QoL.
Results
Thirteen patients were included. Mean age was 60.9 years (range 38-76). Ten had ovarian and 3 had fallopian tube cancer. Six had ≥3 prior regimens. Two had secondary debulking immediately prior to study therapy. Median number of cycles was 6 (range 1-10). Ten patients had measureable disease. Of these, best response was partial response (PR-2), stable disease (SD-7), and progressive disease (1). A total of 21 grade 3-4 toxicities were noted, most commonly hematologic. Two patients had DLTs: prolonged neutropenia (1) and abdominal pain (1). Four patients had treatment delay and 3 had dose reduction. Treatment ended due to disease progression (7), toxicity (4), and remission (2). MTD was d1 docetaxel 75 mg/m2 IV and d2 oxaliplatin 50 mg/m2 IP as the escalated IP dose was deemed intolerable. Symptoms peaked during the first week after treatment and generally returned to baseline by the second. Well-being decreased initially but improved by cycle 4 for those on dose level 1.
Average unbound platinum AUC0-24 and Cmax in IP fluid for 50mg/m2 were 21.01 µg/mL•h and 6.70 µg/mL, respectively. Mean AUC0-24 and Cmax pharmacological advantage for unbound platinum were estimated at 8.58 and 49.98. At 75mg/m2 the mean unbound platinum AUC and Cmax were 55.92 µg/mL•h and 13.89 µg/mL, respectively. Mean AUC and Cmax pharmacologic advantage were estimated at 17.9 and 73.13. Mean plasma AUC0-last for docetaxel was 2290 ng/mL•h.
Conclusions
Docetaxel 75 mg/m2 IV on d1 and oxaliplatin 50 mg/m2 IP on d2 is the MTD. Most patients had PR or SD, even in a heavily pretreated population. At this dose level, patient-reported outcomes demonstrate temporary but tolerable decrements in QoL, IP oxaliplatin provides a significant peritoneal PK advantage.
Citation Format: Sarah E. Taylor, Ruosha Li, Jennifer S. Petschauer, Heidi Donovan, William C. Zamboni, Robert P. Edwards, Kristen K. Zorn. Phase I study of intraveneous docetaxel and intraperitoneal oxaliplatin in recurrent ovarian, fallopian tube and peritoneal cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr CT412. doi:10.1158/1538-7445.AM2014-CT412