title: In vitro chemoresponse in metachronous pairs of gyneclologic cancers.
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
  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.
authors.affiliation: The University of Texas MD Anderson Cancer Center, Houston, TX USA.
authors.forename: Heather J
authors.initials: HJ
authors.lastname: Dalton
authors.affiliation: Sarasota Memorial Hospital, Sarasota, FL USA.
authors.forename: James
authors.initials: J
authors.lastname: Fiorica
authors.affiliation: Precision Therapeutics, Inc, Pittsburgh, PA USA.
authors.forename: Candace K
authors.initials: CK
authors.lastname: McClure
authors.affiliation: University of South Alabama Mitchell Cancer Institute, Mobile, AL USA.
authors.forename: Rodney P
authors.initials: RP
authors.lastname: Rocconi
authors.affiliation: South Florida Center for Gynecologic Oncology, Boca Raton, FL USA.
authors.forename: Fernando O
authors.initials: FO
authors.lastname: Recio
authors.affiliation: North Shore LIJ Health System, Biomedical Research Alliance of New York, Manhassett, NY USA.
authors.forename: John L
authors.initials: JL
authors.lastname: Levocchio
authors.affiliation: Georgia Gynecologic Oncology, Atlanta, GA USA.
authors.forename: Matthew O
authors.initials: MO
authors.lastname: Burrell
authors.affiliation: University of Arizona Cancer Center, Creighton University School of Medicine at Dignity Health St. Joseph's Hospital and Medical Center, 500 W. Thomas Road, Suite 600, Phoenix, AZ 85013 USA.
authors.forename: Bradley J
authors.initials: BJ
authors.lastname: Monk
keywords: Chemotherapy; Cross-resistance; Drug resistance; Gynecologic cancer; Recurrent ovarian