Randomized, Multicenter, Phase II Study of CO-101 Versus Gemcitabine in Patients With Metastatic Pancreatic Ductal Adenocarcinoma: Including a Prospective Evaluation of the Role of hENT1 in Gemcitabine or CO-101 Sensitivity

Poplin, Elizabeth; Wasan, Harpreet; Rolfe, Lindsey; Raponi, Mitch; Ikdahl, Tone; Bondarenko, Igor; Давиденко, Ірина; Бондарь, В. Ю.; Garin, A.; Boeck, Stefan; Ormanns, Steffen; Heinemann, Volker; Bassi, Claudio; Evans, T.R.J.; Andersson, Roland; Hahn, Hejin P.; Picozzi, Vince; Dicker, Adam P.; Mann, Elaina; Voong, Cynthia; Kaur, Paramjit; Isaacson, Jeff; Allen, Andrew R.

doi:10.1200/jco.2013.51.0826

Cited by 151 publications

(126 citation statements)

References 23 publications

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“…CA 19-9 has been used as a diagnostic and prognostic marker, but no data exist to suggest that patients with a particular level of CA 19-9 would benefit from one treatment over another (1). Human equilibrative nucleoside transporter (hENT1) has demonstrated some promise in predicting response to gemcitabine in the adjuvant setting (29,30); however, the only prospective study to date of hENT1 in patients with MPC revealed no association of hENT1 level with efficacy (31). A number of other biomarkers, such as carcinoembryonic antigen (CEA), pancreatic antioncofetal antigen, tissue polypeptide antigen, and cancer antigen 125 (CA 125), have been studied in pancreatic cancer (1), but more research is needed to validate their utility.…”

Section: (32)mentioning

confidence: 99%

SPARC Expression Did Not Predict Efficacy of nab-Paclitaxel plus Gemcitabine or Gemcitabine Alone for Metastatic Pancreatic Cancer in an Exploratory Analysis of the Phase III MPACT Trial

Hidalgo

Plaza

Musteanu

et al. 2015

Clinical Cancer Research

118

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Purpose: nab-Paclitaxel plus gemcitabine was superior to gemcitabine alone for patients with metastatic pancreatic cancer (MPC) in the phase III MPACT trial. This study evaluated the association of secreted protein acidic and rich in cysteine (SPARC) levels with efficacy as an exploratory endpoint.Experimental Design: Patients with previously untreated MPC (N ¼ 861) received nab-paclitaxel plus gemcitabine or gemcitabine alone. Baseline SPARC level was measured in the tumor stroma and epithelia (archival biopsies) and plasma. Experiments were performed in pancreatic cancer mouse models in which SPARC was intact or deleted.Results: SPARC was measured in the tumor stroma of 256 patients (30%), the tumor epithelia of 301 patients (35%), and plasma of 343 patients (40%). Stroma-evaluable samples were from metastases (71%), from the pancreas (11%), or of unidentifiable origin (insufficient tissue to determine; 17%). For all patients, stromal SPARC level [high (n ¼ 71) vs. low (n ¼ 185)] was not associated with overall survival (OS; HR, 1.019; P ¼ 0.903); multivariate analysis confirmed this lack of association. There was no association between stromal SPARC level and OS in either treatment arm. Neither tumor epithelial SPARC nor plasma SPARC was associated with OS. Results from a SPARC knockout mouse model treated with nab-paclitaxel plus gemcitabine revealed no correlation between SPARC expression and tumor progression or treatment efficacy.Conclusions: SPARC levels were not associated with efficacy in patients with MPC. This exploratory analysis does not support making treatment decisions regarding nab-paclitaxel plus gemcitabine or gemcitabine alone in MPC based on SPARC expression.

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Section: (32)mentioning

confidence: 99%

SPARC Expression Did Not Predict Efficacy of nab-Paclitaxel plus Gemcitabine or Gemcitabine Alone for Metastatic Pancreatic Cancer in an Exploratory Analysis of the Phase III MPACT Trial

Hidalgo

Plaza

Musteanu

et al. 2015

Clinical Cancer Research

118

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“…All studies using the above murine antibody demonstrated a significant predictive value in response to gemcitabine in an adjuvant setting only (38-40) whereas those using the aforementioned rabbit monoclonal antibody did not (41). Data on advanced pancreatic cancer are scarce, with only two studies published to date, both of which used the SP120 rabbit monoclonal antibody to measure hENT1 expression, and no evidence of predictive value was identified (42,43). Thus, the role of hENT1 as a predictive marker of gemcitabine efficacy remains unclear, particularly in a metastatic pancreatic cancer setting.…”

Section: Discussionmentioning

confidence: 99%

Use of gemcitabine as a second-line treatment following chemotherapy with folfirinox for metastatic pancreatic adenocarcinoma

et al. 2017

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Abstract. There is a lack of prospective data about second-line treatments for metastatic pancreatic ductal adenocarcinoma patients. This is partially due to recent changes in first-line chemotherapy treatments. Despite this dearth of information, 50.0% of the patients who experience failure with first-line folinic acid, 5-fluorouracil, irinotecan and oxaliplatin (folfirinox) treatment are eligible for additional chemotherapy.

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“…Экспрессия hENT1, определяемая иммуногистохимически в опухоли с помощью антитела 10D7G2, оказалась пре-диктором повышенной эффективно-сти гемцитабина у пациентов, полу-чавших гемцитабин в адъювантном режиме в исследованиях ESPAC-3 и RTOG 9704 [54,55]. Предиктив ная роль hENT1 не была подтверждена при использовании другого антитела SP120 [56][57][58]. Возможной причиной расхождения результатов является плохая конкордантность данных антител [59].…”

Section: возможности индивидуализации терапии рака поджелудочной железыunclassified

Combination Chemotherapy Regimens in Pancreatic Cancer

Попова¹,

Pokataev²,

Тюляндин³

2017

Med. sov.

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Рак поджелудочной железы характеризуется агрессивным течением и высоким метастатическим потенциалом, в связи с чем в большинстве случаев заболевание выявляется на неоперабельных стадиях. Основным методом лечения местнораспро-страненного и метастатического рака поджелудочной железы является химиотерапия. До недавнего времени стандартом химиотерапии данной патологии считалась монотерапия гемцитабином, пока в клиническую практику не вошли более эффективные режимы комбинированной химиотерапии (FOLFIRINOX и комбинация nab-паклитаксела с гемцитабином). Назначение данных схем химиотерапии лимитирует относительно высокая токсичность, что делает невозможным их при-менение у ослабленных пациентов и у больных с серьезной сопутствующей патологией. В настоящей работе рассматривают-ся критерии выбора оптимального режима комбинированной химиотерапии на основе оценки состояния пациента, возмож-ности управления побочными эффектами химиотерапии, а также молекулярно-биологические характеристики опухоли.

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Randomized, Multicenter, Phase II Study of CO-101 Versus Gemcitabine in Patients With Metastatic Pancreatic Ductal Adenocarcinoma: Including a Prospective Evaluation of the Role of hENT1 in Gemcitabine or CO-101 Sensitivity

Abstract: CO-101 is not superior to gemcitabine in patients with mPDAC and low tumor hENT1. Metastasis hENT1 expression did not predict gemcitabine outcome.

Cited by 151 publications

References 23 publications

SPARC Expression Did Not Predict Efficacy of nab-Paclitaxel plus Gemcitabine or Gemcitabine Alone for Metastatic Pancreatic Cancer in an Exploratory Analysis of the Phase III MPACT Trial

SPARC Expression Did Not Predict Efficacy of nab-Paclitaxel plus Gemcitabine or Gemcitabine Alone for Metastatic Pancreatic Cancer in an Exploratory Analysis of the Phase III MPACT Trial

Use of gemcitabine as a second-line treatment following chemotherapy with folfirinox for metastatic pancreatic adenocarcinoma

Combination Chemotherapy Regimens in Pancreatic Cancer

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