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.
OBJECTIVE: The in vitro microculture kinetic (MiCK) apoptosis assay has been used to predict single or combination chemotherapy response in leukemiapatients. 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 cancerpatient's chemotherapy management.
Entities:
Keywords:
Chemosensitivity assay; Chemotherapy; Endometrial cancer
Authors: J Tate Thigpen; Mark F Brady; Howard D Homesley; John Malfetano; Brent DuBeshter; Robert A Burger; Shu Liao Journal: J Clin Oncol Date: 2004-10-01 Impact factor: 44.544
Authors: Gini F Fleming; Virginia L Brunetto; David Cella; Katherine Y Look; Gary C Reid; Adnan R Munkarah; Richard Kline; Robert A Burger; Annekathryn Goodman; R Tucker Burks Journal: J Clin Oncol Date: 2004-06-01 Impact factor: 44.544
Authors: Yujia Wen; Lidija K Gorsic; Heather E Wheeler; Dana M Ziliak; Rong Stephanie Huang; Mary Eileen Dolan Journal: Pharmacogenet Genomics Date: 2011-08 Impact factor: 2.089
Authors: Emery Salom; Manuel Penalver; Howard Homesley; Matthew Burrell; Audrey Garrett; Cary A Presant; James Rutledge; Michael Chernick; Allan Hallquist; Mathieu Perree Journal: J Transl Med Date: 2012-08-08 Impact factor: 5.531
Authors: E C Grendys; J V Fiorica; J W Orr; R Holloway; D Wang; C Tian; J K Chan; T J Herzog Journal: Clin Transl Oncol Date: 2014-07-02 Impact factor: 3.405
Authors: Linda Bosserman; Karl Rogers; Carl Willis; Dirk Davidson; Pat Whitworth; Misagh Karimi; Gargi Upadhyaya; James Rutledge; Allan Hallquist; Mathieu Perree; Cary A Presant Journal: PLoS One Date: 2015-05-29 Impact factor: 3.240
Authors: Haifeng Qiu; Jing Li; Leslie H Clark; Amanda L Jackson; Lu Zhang; Hui Guo; Joshua E Kilgore; Paola A Gehrig; Chunxiao Zhou; Victoria L Bae-Jump Journal: Oncotarget Date: 2016-10-11