Endometrial carcinoma in vitro chemosensitivity testing of single and combination chemotherapy regimens using the novel microculture kinetic apoptosis assay: implications for endometrial cancer treatment

被引:13
作者
Ballard, Karen S. [1 ]
Homesley, Howard D. [1 ]
Hodson, Charles [1 ]
Presant, Cary A. [2 ]
Rutledge, James [3 ]
Hallquist, Allan [2 ]
Perree, Mathieu [2 ]
机构
[1] E Carolina Univ, Dept Obstet & Gynecol, Brody Sch Med, Greenville, NC 27834 USA
[2] DiaTech Oncol, Nashville, TN USA
[3] Data Vis, Dayton, OH USA
关键词
Chemosensitivity assay; Chemotherapy; Endometrial cancer; PHASE-II TRIAL; RECURRENT ADENOCARCINOMA; PACLITAXEL; CISPLATIN; DOXORUBICIN;
D O I
10.3802/jgo.2010.21.1.45
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Objective: The in vitro microculture kinetic (MiCK) apoptosis assay has been used to predict single or combination chemotherapy response in leukemia patients. This feasibility study addressed MiCK in endometrial cancer specimens. Methods: Endometrial cancer specimens from total abdominal hysterectomies were processed at a central laboratory. Single cell suspensions of viable endometrial cancer cells were plated in individual wells. Single and combination regimens were tested: combinations of doxorubicin, cisplatin, and paclitaxel and carboplatin and paclitaxel (Gynecologic Oncology Group [GOG] 209 endometrial cancer phase III trial arms) as well as single agent testing with paclitaxel, carboplatin, doxorubicin, cisplatin, ifosfamide, and vincristine (active agents in GOG trials). Apoptosis was measured continuously over 48 hours. Results: Fifteen of nineteen patients had successful assays. The highest mean chemo sensitivity was noted in the combination of cisplatin, doxorubicin, and paclitaxel with lower mean chemosensitivity for carboplatin and paclitaxel. Combination chemotherapy had higher chemosensitivity than single drug chemotherapy. However, in 25% of patients a single drug had higher chemosensitivity than combination chemotherapy. As single agents, ifosfamide, cisplatin, and paclitaxel had the highest kinetic unit values. Conclusion: Using a panel of agents simulating clinical dose regimens, the MiCK assay was feasible in evaluating in vitro chemosensitivity of endometrial cancer. MiCK assay results correlated with GOG clinical trial results. However, 25% of patients might be best treated with single agent chemotherapy selected by MiCK. Ifosfamide, cisplatin, and paclitaxel appear to have high activity as single agents. MiCK may be useful in future new drug testing and individualizing endometrial cancer patient's chemotherapy management.
引用
收藏
页码:45 / 49
页数:5
相关论文
共 22 条
[1]   Approximate is better than "exact" for interval estimation of binomial proportions [J].
Agresti, A ;
Coull, BA .
AMERICAN STATISTICIAN, 1998, 52 (02) :119-126
[2]  
[Anonymous], J CLIN ONCOL S
[3]  
[Anonymous], 1989, JMP VERS 7
[4]   A phase II trial of paclitaxel in patients with advanced or recurrent adenocarcinoma of the endometrium: A Gynecologic Oncology Group study [J].
Ball, HG ;
Blessing, JA ;
Lentz, SS ;
Mutch, DG .
GYNECOLOGIC ONCOLOGY, 1996, 62 (02) :278-281
[5]   A PHASE-II TRIAL OF VINCRISTINE IN ADVANCED OR RECURRENT ENDOMETRIAL CARCINOMA - A GYNECOLOGIC ONCOLOGY GROUP-STUDY [J].
BROUN, GO ;
BLESSING, JA ;
EDDY, GL ;
ADELSON, MD .
AMERICAN JOURNAL OF CLINICAL ONCOLOGY-CANCER CLINICAL TRIALS, 1993, 16 (01) :18-21
[6]   Phase III trial of doxorubicin plus cisplatin with or without paclitaxel plus filgrastim in advanced endometrial carcinoma: A gynecologic oncology group study [J].
Fleming, GF ;
Brurietto, VL ;
Cella, D ;
Look, KY ;
Reid, GCH ;
Munkarah, AR ;
Kline, R ;
Burger, RA ;
Goodman, A ;
Burks, RT .
JOURNAL OF CLINICAL ONCOLOGY, 2004, 22 (11) :2159-2166
[7]  
Kravtsov VD, 1998, BLOOD, V92, P968
[8]  
Kravtsov VD, 1996, LAB INVEST, V74, P557
[9]   Comparative analysis of different methodological approaches to the in vitro study of drug-induced apoptosis [J].
Kravtsov, VD ;
Daniel, TO ;
Koury, MJ .
AMERICAN JOURNAL OF PATHOLOGY, 1999, 155 (04) :1327-1339