Phase I study of intravenous (IV) docetaxel and intraperitoneal (IP) oxaliplatin in recurrent ovarian and fallopian tube cancer

被引:6
作者
Taylor, Sarah E. [1 ]
Li, Ruosha [2 ]
Petschauer, Jennifer S. [3 ]
Donovan, Heidi [2 ]
O'Neal, Sara [3 ]
Keeler, Amanda W. [3 ]
Zamboni, William C. [3 ]
Edwards, Robert P. [1 ]
Zorn, Kristin K. [4 ]
机构
[1] UPMC, Magee Womens Hosp, Div Gynecol Oncol, Pittsburgh, PA USA
[2] Univ Pittsburgh, Sch Nursing, Pittsburgh, PA 15261 USA
[3] Univ N Carolina, Eshelman Sch Pharm, Div Pharmacotherapy & Expt Therapeut, Chapel Hill, NC USA
[4] Univ Arkansas, Med Sci, Little Rock, AR 72204 USA
关键词
Intraperitoneal chemotherapy; Ovarian cancer; Recurrent; Phase I trial; GYNECOLOGIC-ONCOLOGY-GROUP; PRETREATED PATIENTS; PLATINUM-RESISTANT; PACLITAXEL; CHEMOTHERAPY; CISPLATIN; TRIAL; PHARMACOKINETICS; GEMCITABINE; COMBINATION;
D O I
10.1016/j.ygyno.2015.06.026
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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/m(2) IV day (d) 1 and oxaliplatin escalating from 50 mg/m(2) 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 Grades 3-4 toxicities were noted, commonly hematologic. Two patients had DLTs: prolonged neutropenia (1) and abdominal pain (1). MTD was d1 docetaxel 75 mg/m(2) IV and d2 oxaliplatin 50 mg/m(2) IP. Symptom burden peaked week one and returned to baseline by week two of each cycle on dose level I. Dose level 2 had persistently high symptom burden and interference. At IP oxaliplatin doses of 50 mg/m(2), 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/m(2) IV d1 and oxaliplatin 50 mg/m(2) IP d2 is the MM. Most patients had PR or SD. Patient-reported outcomes demonstrate temporary but tolerable decrements in QoL. IP oxaliplatin provides PK advantages over IV administration. (C) 2015 Elsevier Inc. All rights reserved.
引用
收藏
页码:548 / 553
页数:6
相关论文
共 26 条
[1]   Intraperitoneal cisplatin plus intravenous cyclophosphamide versus intravenous cisplatin plus intravenous cyclophosphamide for stage III ovarian cancer [J].
Alberts, DS ;
Liu, PY ;
Hannigan, EV ;
OToole, R ;
Williams, SD ;
Young, JA ;
Franklin, EW ;
ClarkePearson, DL ;
Malviya, VK ;
DuBeshter, B ;
Adelson, MD ;
Hoskins, WJ .
NEW ENGLAND JOURNAL OF MEDICINE, 1996, 335 (26) :1950-1955
[2]  
[Anonymous], 2004, OX PACK INS, P10016
[3]   Intraperitoneal cisplatin and paclitaxel in ovarian cancer [J].
Armstrong, DK ;
Bundy, B ;
Wenzel, L ;
Huang, HQ ;
Baergen, R ;
Lele, S ;
Copeland, LJ ;
Walker, JL ;
Burger, RA .
NEW ENGLAND JOURNAL OF MEDICINE, 2006, 354 (01) :34-43
[4]  
Chollet P, 1996, ANN ONCOL, V7, P1065
[5]  
Cleeland CS, 2000, CANCER-AM CANCER SOC, V89, P1634, DOI 10.1002/1097-0142(20001001)89:7<1634::AID-CNCR29>3.0.CO
[6]  
2-V
[7]   Phase I safety and pharmacokinetic study of SU-014813 in combination with docetaxel in patients with advanced solid tumours [J].
de Jonge, M. J. A. ;
Dumez, H. ;
Kitzen, J. J. E. M. ;
Beuselinck, B. ;
Verweij, J. ;
Courtney, R. ;
Battista, A. ;
Brega, N. ;
Schoffski, R. .
EUROPEAN JOURNAL OF CANCER, 2011, 47 (09) :1328-1335
[8]   Evaluation of the Symptom Representation Questionnaire (SRQ) for assessing cancer-related symptoms [J].
Donovan, Heidi Scharf ;
Ward, Sandra ;
Sherwood, Paula ;
Serlin, Ronald C. .
JOURNAL OF PAIN AND SYMPTOM MANAGEMENT, 2008, 35 (03) :242-257
[9]  
Extra JM, 1998, SEMIN ONCOL, V25, P13
[10]   Phase II study of oxaliplatin in platinum-resistant and refractory ovarian cancer: A gynecologic group study [J].
Fracasso, PM ;
Blessing, JA ;
Morgan, MA ;
Sood, AK ;
Hoffman, JS .
JOURNAL OF CLINICAL ONCOLOGY, 2003, 21 (15) :2856-2859