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Moore K.N.,University of Oklahoma | Tian C.,Gynecologic Oncology Group Statistical Center | McMeekin D.S.,University of Oklahoma | Thigpen J.T.,University of Mississippi Medical Center | And 2 more authors.

Background: This study evaluated whether progression-free interval (PFI) following primary chemotherapy (PCT) was predictive of overall survival (OS) after second-line chemotherapy in advanced/recurrent endometrial cancer (EC). Methods: This is a pooled analysis of patients who recurred after PCT and were treated with second-line chemotherapy on Gynecologic Oncology Group trials. PFI-1 measured from initiation of PCT to recurrence or treatment-free interval (TFI) measured from completion of PCT to initiation of second-line chemotherapy was evaluated in relation to clinical outcomes. Results: A total of 586 patients treated on 5 phase 3 PCT protocols were included. Baseline factors in primary setting associated with clinical outcome after PCT were also predictive of OS after second-line chemotherapy, including race, Gynecologic Oncology Group performance status, grade, and prior radiation therapy (P <.01). PFI-1 was the most significant factor predictive of survival after second-line chemotherapy, with a 30% reduction in the risk of death for PFI-1 >6 months compared with ≤6 months (hazard ratio [HR], 0.70; 95% confidence interval [CI], 0.59-0.84 [P <.0001]) and median OS after second-line chemotherapy of 10 versus 5 months. A total of 275 patients treated on 9 phase 2 second-line chemotherapy protocols were also evaluated, and TFI >3 months was associated with a 25% reduction in the risk of death (HR, 0.75; 95% CI, 0.57-0.97 [P =.030]) and median OS after second-line chemotherapy of 10 versus 7 months compared with TFI a;circ3 months. The tumor response to second-line chemotherapy was 9.6% versus 5.8%; the difference was not statistically significant. Conclusions: Time to recurrence after PCT is predictive of survival after recurrence in advanced/recurrent EC. However, there is no evidence that this variable can be used in selecting salvage chemotherapy. Cancer 2010. © 2010 American Cancer Society. Time to recurrence after primary chemotherapy is predictive of survival after recurrence in advanced endometrial cancer. However, there is no evidence that this variable provides significant prognostic information or can be used in selecting salvage chemotherapy. Copyright © 2010 American Cancer Society. Source

Dalton H.J.,University of Texas M. D. Anderson Cancer Center | Fiorica J.V.,First Physicians Group Gynecologic Oncology | Edwards R.P.,University of Pittsburgh | Benjamin I.,Arizona Cancer Center | And 8 more authors.
Anticancer Research

Background/Aim: An in vitro chemoresponse assay may aid effective therapy selection in epithelial ovarian cancer (EOC). This study explores changes in chemoresponse between paired primary and recurrent EOC tumors. Patients and Methods: Results from metachronous tumors were examined in 242 patients. Changes in in vitro chemoresponse, measured by the area under the dose response curve (AUC) between paired tumors were assessed. Results: A significant increase in AUC was identified in most first-line therapies over time. No significant difference was observed in most recurrent therapies. When the elapsed time between occurrences was <17 months, no difference was observed for any recurrent therapies, and half of first-line therapies exhibited significant increases in AUC. When ≥17 months, all 7 therapies showed significant increases. Conclusion: These results suggest an increase in chemoresistance over time, which is more pronounced for first-line therapies. This is consistent with clinical observations and suggests the biologic concordance between assay results and response to chemotherapy. Source

Grendys Jr. E.C.,Florida Gynecologic Oncology and Regional Cancer Center | Fiorica J.V.,First Physicians Group Gyn Onc | Orr Jr. J.W.,Florida Gynecologic Oncology and Regional Cancer Center | Holloway R.,Florida Hospital Cancer Institute | And 4 more authors.
Clinical and Translational Oncology

The objective of this review is to summarize recent scientific and medical literature regarding chemoresponse assays or chemotherapy sensitivity and resistance assays (CSRAs), specifically as applied to epithelial ovarian cancer. A total of sixty-seven articles, identified through PubMed using the key words "in vitro chemoresponse assay," "chemo sensitivity resistance assay," "ATP," "HDRA," "EDR," "MiCK," and "ChemoFx," were reviewed. Recent publications on marker validation, including relevant clinical trial designs, were also included. Recent CSRA research and clinical studies are outlined in this review. Published findings demonstrate benefits regarding patient outcome with respect to recent CSRAs. Specifically, analytical and clinical validations, as well as clinical utility and economic benefit, of the most common clinically used CSRA in the United States support its use to aid in making effective, individualized clinical treatment selections for patients with ovarian cancer. © 2014 The Author(s). Source

Plamadeala V.,Precision Therapeutics | Huang S.,Precision Therapeutics | McCreary S.M.,Precision Therapeutics | Reitze N.J.,Precision Therapeutics | And 6 more authors.
Applied Immunohistochemistry and Molecular Morphology

A formalin-fixed paraffin-embedded tissue-based prognostic assay to assess the risk for recurrence in stage II colon cancer has recently been clinically validated. This study describes the analytical performance and quality control measures of the assay. The reportable range was determined to be [-1.129, 1.414] in risk score units. The accuracy was evaluated with a split sample comparison within the production lab and between the production lab and a reference lab. The concordance between the replicates within the production lab was 79% (95% confidence interval, 64%-91%). There was no evidence of bias, and the concordance was 78% (95% confidence interval, 61%-90%) between the labs. The lab-to-lab concordance was further evaluated by simulating risk scores from the full reportable range. The simulation suggested a higher concordance. The sensitivity study demonstrated that the percentage of tumor tissue did not impact the risk score and that RNA concentration of 9.5 ng/μL was a conservative determination of the analyte lower limit of quantification. From the precision study, the repeatability and reproducibility estimates were 0.1267 and 0.0548 in risk score units, respectively. Furthermore, multifaceted quality control measures were implemented, such as proper tissue processing steps, high-risk and low-risk controls, nontemplate control, and a gene expression-based classifier to evaluate the cDNA amplification kit, a key reagent in the assay. In conclusion, this study demonstrates the strong analytical performance of the assay and further supports its use as an objective standardized prognostic test for stage II colon cancer. © 2013 by Lippincott Williams and Wilkins. Source

Suchy S.L.,Precision Therapeutics | Landreneau R.J.,University of Pittsburgh | Schuchert M.J.,University of Pittsburgh | Wang D.,Precision Therapeutics | And 2 more authors.
Cancer Biology and Therapy

Purpose: Pemetrexed is the only FDA approved treatment for mesothelioma and is a second line agent for treatment of non-small cell lung carcinoma (NSCLC). Pemetrexed is inhibited by folate and its analogs, which are components of many culture media, making it challenging to study pemetrexed in vitro. In order to accurately evaluate pemetrexed's effects in vitro, the protocol for a standard chemosensitivity assay, the ChemoFx drug response marker, had to be modified. Experimental Design: Novel rinse and media change steps were assessed and then added to the assay protocol in order to observe pemetrexed activity. The intraday and interday stability of pemetrexed were also established under the adapted protocol. Then, the modified protocol was used to examine pemetrexed in 65 ex vivo lung cancer specimens. Results: Substituting 5% RPMI + EGF for BEGM allowed pemetrexed to exert its anticancer activity in the ChemoFx DRM. ChemoFx classified 6.2% of the lung specimens as responsive, 9.2% as intermediate responsive and 84.6% as non-responsive to pemetrexed. Conclusions: Adapting the ChemoFx protocol allowed for the accurate evaluation of pemetrexed anticancer activity in ex vivo lung specimens. ChemoFx evaluation may provide an indication of a patient's clinical response to the drug prior to pemetrexed treatment. Having this information when treatment options are being considered could avoid wasted time, unnecessary costs and needless side effects that are the result of an inappropriate chemotherapy regimen. © 2013 Landes Bioscience. Source

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