Evaluation of in vitro chemoresponse profiles in women with Type I and Type II epithelial ovarian cancers: An observational study ancillary analysis

Previs, Rebecca A.; Leath, Charles A.; Coleman, Robert L.; Herzog, Thomas J.; Krivak, Thomas C.; Brower, Stacey L.; Tian, Chunqiao; Secord, Angeles Alvarez

doi:10.1016/j.ygyno.2015.05.038

Cited by 10 publications

(12 citation statements)

References 29 publications

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“…Specifically, women whose tumor specimens demonstrated in vitro platinum resistance were at higher risk for disease progression compared to those with sensitive or intermediate sensitive assay results (median PFS: 11.8 vs 16.6 months, respectively, P < .001) [6]. In addition, our group compared in vitro assay response between Type I and Type II EOC and found that, despite the dogmatic belief that Type I EOC are chemoresistant, the majority (86%) of Type I tumors were chemosensitive to at least one cytotoxic agent and 35.7% were pan-S to all 7 agents tested [14]. Multi-drug resistance was twice as likely in women with Type I EOC compared to Type II EOC (pan-R, 14.3 vs. 6.8% ( p = 0.268); pan-S, 35.7 vs. 51.2% ( p = 0.183)), but did not reach statistical significance.…”

Section: Discussionmentioning

confidence: 99%

Analysis of in vitro chemoresponse assays in endometrioid endometrial adenocarcinoma: an observational ancillary analysis

Davidson

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Brower³

et al. 2016

gynaecol oncol res pract

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BackgroundChemotherapy plays a role in the treatment of endometrioid endometrial cancer (EEC); however, tumor grade may affect response. Our objective was to evaluate associations between tumor grade and in vitro chemoresponse.MethodsWe conducted an analysis of primary tumor samples from women with EEC undergoing in vitro chemoresponse testing. Results were classified as sensitive (S), intermediate (I), or resistant (R) to each drug tested. Correlations between tumor grade and response were examined.ResultsData was collected from 159 patients: 28 with grade 1 (18%), 52 with grade 2 (32%), and 79 (50%) with grade 3 tumors. Median age of patients was 62 (range 31–92). Most patients were Caucasian (83%) with advanced disease (Stage III: 50.9%; Stage IV: 13.2%). Overall chemoresponse was similar across all grades. Fifty percent, 56 and 51% for grade 1, 2, and 3 tumors, respectively, demonstrated S results to at least 1 agent. There was no association between grade and in vitro response to chemotherapy agents (p > 0.05) except a marginal association between grade and doxorubicin response (p = 0.08). Grade 1 and 2 cancers were more likely to demonstrate R results for doxorubicin compared to grade 3 cancers (G1: 19% vs G2: 25% vs G3: 8%; p = 0.08). In a subset tested for all 7 agents, only one patient tumor was pan-R and 4 were pan-S.ConclusionsBased on our data, grades 1–3 EEC have similar in vitro chemoresponse. These findings suggest that chemotherapy may be useful in advanced low grade EECs, but further clinical correlation is needed.

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Section: Discussionmentioning

confidence: 99%

Analysis of in vitro chemoresponse assays in endometrioid endometrial adenocarcinoma: an observational ancillary analysis

Davidson

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Brower³

et al. 2016

gynaecol oncol res pract

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“…In addition, in the subgroup of patients treated with assay-sensitive agents, progression-free survival (PFS) and OS are found to be improved, and further analysis has confirmed these results (14,15). Recently, an observational study has also evaluated chemosensitivity profiles of type 1 and type 2 epithelial ovarian cancer (EOC) (16). There is a dearth of large randomized prospective trials for ovarian cancer evaluating the survival of patients treated by empirically decided therapy versus selected chemotherapeutic regimen based on the in vitro chemosensitivity assay results (assay-directed therapy).…”

Section: Introductionmentioning

confidence: 88%

In vitro chemosensitivity in ovarian carcinoma: Comparison of three leading assays

Tatar

Boyraz

Selçuk

et al. 2016

J Turkish German Gynecol Assoc

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Material and Methods:Fresh tumoral tissue samples of 26 newly diagnosed primary ovarian cancer patients were studied with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolyum bromide (MTT) assay, adenosine triphosphate-tumor chemosensitivity assay (ATP-TCA) and differential staining cytotoxicity (DISC) assays. Chemosensitivity of tumors were studied for paclitaxel, carboplatin, docetaxel, topotecan, gemcitabine, and doxorubicin with each of the three assays. Subgroup analysis was performed for stage, grade, and histologic type. Results:The in vitro chemosensitivity results of MTT, ATP, and DISC assays were found to be similar. The subgroups in which in vitro assays would be more useful were encountered for patients with advanced stage and serous histology ovarian carcinoma. Conclusions:In vitro chemosensitivity can be determined in ovarian carcinoma with ATP, MTT, or DISC assays before the initiation of chemotherapy. These three assays correlate well with each other and are particularly useful for serous and advanced cancers. Large prospective studies comparing standard versus assay-directed therapy with an endpoint of overall survival are required before routine clinical utilization of these assays. (J Turk Ger Gynecol Assoc 2016; 17: 35-40) Keywords: Ovarian cancer, in vitro chemosensitivity, ATP, MTT, DISC Received: 20 January, 2016 Accepted: 22 January, 2016 In vitro chemosensitivity in ovarian carcinoma:Comparison of three leading assays Black and Speer in 1950s (9). The chemosensitivity tests allow detecting the cytotoxic, cytostatic, and apoptotic effects of the chemotherapeutic agent outside the organism. Such an approach is particularly thought to prevent the harmful toxic effects of these agents. Many molecular and cellular assays have been developed to date for the in vitro detection of chemosensitivity. The molecular methods detect the chemosensitivity at the protein or gene level (10,11). Although a single gene may be sufficient for the evaluation, a cytotoxic drug sometimes generates an excessive cellular response (12, 13). Cellular methods provide the efficacy results for multiple drugs simultaneously. Several tests based on cellular methods, including 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolyum bromide (MTT) chemosensitivity assay, adenosine triphosphate-tumor chemosensitivity assay (ATP-TCA), and differential staining cytotoxicity (DISC) assays, have been described in the literature. Despite the logic that any method that predicts the chemosensitivity of a tumor for an individual patient would be helpful for better regimens, no chemosensitivity assay has achieved widespread clinical use to date. In a study from USA with 262 patients, all the patients were treated empirically, but a chemosensitivity assay was also performed concomitantly for all. In addition, in the subgroup of patients treated with assay-sensitive agents, progression-free survival (PFS) and OS are found to be improved, and further analysis has confirmed these results (14,15). Recently, an observational study h...

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“…Importantly, the chemoresponse assay identified at least one alternative chemotherapy option that was either sensitive or intermediate-sensitive in nearly 60% of carboplatin-resistant tumors, indicating that use of the chemoresponse assay to select therapy may provide an opportunity to improve patient outcomes by informing more effective first-line treatment options. In addition, an exploratory ancillary data analysis compared pre-treatment chemoresponse assay results in 383 women with advanced stage Type I and Type II disease [62]. Thirty women were classified as Type I (grade 1 serous and endometrioid as well as clear cell and mucinous cancers) and the remaining 353 were classified as Type II (grade 2–3 serous and endometrioid as well as undifferentiated cancers).…”

Section: Predictors Of Outcome In Patients Treated With Chemotheramentioning

confidence: 99%

“… CI, confidence interval; EOC, epithelial ovarian cancer; HR, hazard ratio; ICER/LYS, incremental cost-effectiveness rating per life-year saved; OS, overall survival; PFI, progression-free interval; PFS, progression-free survival. a Reference 64, b reference 61, c reference 63, d reference 58, e reference 11, f reference 62, g reference 66, h reference 65, i reference 25, j reference 68, k reference 67. …”

Section: Figmentioning

confidence: 99%

Evolution of Chemosensitivity and Resistance Assays as Predictors of Clinical Outcomes in Epithelial Ovarian Cancer Patients

Monk

Herzog²,

Tewari³

2016

CPD

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Epithelial ovarian cancer (EOC) is responsible for more cancer-related deaths than any other malignancy of the female reproductive system. The standard of care for advanced EOC involves a combination of cytoreductive surgery and platinum-based chemotherapy. Although a majority of patients respond to a platinum-containing regimen, many fail to respond to first-line treatment (platinum-refractory disease) or experience disease progression within 6 months of completing treatment (platinum-resistant disease). Even in patients who initially respond to platinum-based therapy, secondary development of platinum resistance is common. Many chemotherapeutic regimens with comparable efficacy and toxicities are available, leaving the determination of optimal therapy to the physician’s discretion. There have been many efforts over the years to develop accurate predictors of outcomes in patients treated with chemotherapy to help inform treatment decisions. Predictive treatment markers are particularly relevant in a disease such as EOC, where a large number of similarly efficacious chemotherapy regimens are available. Chemosensitivity and resistance assays (CSRAs) are attractive approaches to interrogate the efficacy and complex biology of EOC. Some early predictive cellular tests, such as the early clonogenic assays, were limited by technical and logistical issues. Over time, changes in these assays have improved their prognostic and predictive value, but there is still a lack of widespread adoption due to methodological difficulties or limited clinical validation. Herein, we provide an overview of the evolution of CSRAs used to predict outcomes in patients treated with chemotherapy that have been evaluated for use in EOC, with a focus on the latest generation chemoresponse assay.

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Evaluation of in vitro chemoresponse profiles in women with Type I and Type II epithelial ovarian cancers: An observational study ancillary analysis

Cited by 10 publications

References 29 publications

Analysis of in vitro chemoresponse assays in endometrioid endometrial adenocarcinoma: an observational ancillary analysis

Analysis of in vitro chemoresponse assays in endometrioid endometrial adenocarcinoma: an observational ancillary analysis

In vitro chemosensitivity in ovarian carcinoma: Comparison of three leading assays

Evolution of Chemosensitivity and Resistance Assays as Predictors of Clinical Outcomes in Epithelial Ovarian Cancer Patients

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