Phase I Study of IV Docetaxel and IP Oxaliplatin in Recurrent Ovarian and Fallopian Tube Cancer

abstract
 

Highlights

• •We defined the MTD of IV docetaxel and IP oxaliplatin in recurrent ovarian cancer.
• •Most patients had PR or SD, with patient-reported outcomes showing temporary but tolerable decrements in QoL.
• •IP oxaliplatin provides a significant peritoneal PK advantage.

Abstract

Objective

: 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(OV), fallopian tube(FT) or peritoneal(PP) cancer. Secondary objectives included response rate, time to progression, pharmacokinetics(PK) and quality of life(QoL).

Methods

: Patients received docetaxel 75 mg/m² IV day(d) 1 and oxaliplatin escalating from 50 mg/m² IP d2 every 3 weeks using a 3 + 3 design. Treatment continued until disease progression, remission, or intolerable toxicity. Plasma and IP samples were taken to determine drug concentrations. MD Anderson Symptom Inventory and symptom interference scale were completed weekly.

Results

: Thirteen patients were included. Median number of cycles was 6(range 1–10). Ten patients had measureable disease. Best response was partial response(PR-2), stable disease(SD-7), and progressive disease(PD-1). Twenty-one grade 3–4 toxicities were noted, commonly hematologic. Two patients had DLTs: prolonged neutropenia(1) and abdominal pain(1). MTD was d1 docetaxel 75 mg/m² IV and d2 oxaliplatin 50 mg/m² 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 oxaliplatin doses of 50 mg/m², total unbound drug exposure(AUC) averaged 8 times larger and C_max reached concentrations 50-fold greater in IP fluid compared to plasma.

Conclusions

: Docetaxel 75 mg/m² IV d1 and oxaliplatin 50 mg/m² IP d2 is the MTD. Most patients had PR or SD. Patient-reported outcomes demonstrate temporary but tolerable decrements in QoL. IP oxaliplatin provides PK advantages over IV administration.