Heather J Dalton, James Fiorica, Candace K McClure, Rodney P Rocconi, Fernando O Recio, John L Levocchio, Matthew O Burrell, Bradley J Monk
{"title":"In vitro chemoresponse in metachronous pairs of gyneclologic cancers.","authors":"Heather J Dalton, James Fiorica, Candace K McClure, Rodney P Rocconi, Fernando O Recio, John L Levocchio, Matthew O Burrell, Bradley J Monk","doi":"10.1186/2053-6844-1-7","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>While most gynecologic cancers respond to first-line cytotoxic chemotherapy, treatment of recurrent disease is frequently associated with acquired drug resistance. In order to find an in vitro surrogate of this clinical phenomenon, a tumor chemoresponse assay was studied.</p><p><strong>Methods/materials: </strong>Patients who had tissue submitted for repeated chemoresponse testing were identified through a retrospective search. Sixty-three patients met inclusion criteria (chemoresponse testing completed at primary diagnosis and upon recurrence of disease and assays completed ≥90 days apart). The Wilcoxon signed-rank test was used to compare chemoresponse, represented as a response index (RI), between primary and recurrent measurements. In a secondary analysis, response was categorized and coded as Responsive = 3, Intermediately Responsive = 2 and Non-Responsive = 1, and the paired t-test was used to compare chemoresponse between primary and recurrent measurement.</p><p><strong>Results: </strong>Median time between primary and recurrent tumor testing was 309 days (IQR 208-422). Drugs tested included carboplatin, cisplatin, docetaxel, doxorubicin, gemcitabine, paclitaxel, topotecan, and combination carboplatin/gemcitabine and carboplatin/paclitaxel. There were no differences in chemoresponse between primary and recurrent measurement when chemoresponse was represented by RI scores; although a trend toward increased resistance to paclitaxel upon recurrence was noted. When chemoresponse was analyzed as a continuous variable corresponding to categorized response, a significant shift toward increased resistance to paclitaxel at recurrence, and a marginally significant trend toward increased resistance to carboplatin at recurrence, were observed.</p><p><strong>Conclusions: </strong>We observed a trend toward increased chemoresistance at recurrence for paclitaxel, and a marginally significant trend toward increased chemoresistance to carboplatin, but no change in chemoresponsiveness between primary diagnosis and recurrence of disease for other common chemotherapy drugs, including common second-line agents such as doxorubicin, gemcitabine, and topotecan.</p>","PeriodicalId":91487,"journal":{"name":"Gynecologic oncology research and practice","volume":"1 ","pages":"7"},"PeriodicalIF":0.0000,"publicationDate":"2014-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/2053-6844-1-7","citationCount":"1","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Gynecologic oncology research and practice","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1186/2053-6844-1-7","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2014/1/1 0:00:00","PubModel":"eCollection","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 1
Abstract
Background: While most gynecologic cancers respond to first-line cytotoxic chemotherapy, treatment of recurrent disease is frequently associated with acquired drug resistance. In order to find an in vitro surrogate of this clinical phenomenon, a tumor chemoresponse assay was studied.
Methods/materials: Patients who had tissue submitted for repeated chemoresponse testing were identified through a retrospective search. Sixty-three patients met inclusion criteria (chemoresponse testing completed at primary diagnosis and upon recurrence of disease and assays completed ≥90 days apart). The Wilcoxon signed-rank test was used to compare chemoresponse, represented as a response index (RI), between primary and recurrent measurements. In a secondary analysis, response was categorized and coded as Responsive = 3, Intermediately Responsive = 2 and Non-Responsive = 1, and the paired t-test was used to compare chemoresponse between primary and recurrent measurement.
Results: Median time between primary and recurrent tumor testing was 309 days (IQR 208-422). Drugs tested included carboplatin, cisplatin, docetaxel, doxorubicin, gemcitabine, paclitaxel, topotecan, and combination carboplatin/gemcitabine and carboplatin/paclitaxel. There were no differences in chemoresponse between primary and recurrent measurement when chemoresponse was represented by RI scores; although a trend toward increased resistance to paclitaxel upon recurrence was noted. When chemoresponse was analyzed as a continuous variable corresponding to categorized response, a significant shift toward increased resistance to paclitaxel at recurrence, and a marginally significant trend toward increased resistance to carboplatin at recurrence, were observed.
Conclusions: We observed a trend toward increased chemoresistance at recurrence for paclitaxel, and a marginally significant trend toward increased chemoresistance to carboplatin, but no change in chemoresponsiveness between primary diagnosis and recurrence of disease for other common chemotherapy drugs, including common second-line agents such as doxorubicin, gemcitabine, and topotecan.