Publications by authors named "Ihor Bondarenko"

2 Publications

  • Page 1 of 1

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.

J Clin Oncol 2013 Dec 12;31(35):4453-61. Epub 2013 Nov 12.

Elizabeth Poplin, Cancer Institute of New Jersey, New Brunswick, NJ; Mitch Raponi, Elaina Mann, Cynthia Voong, and Andrew Allen, Clovis Oncology, San Francisco, CA; Hejin Hahn and Vince Picozzi, Virginia Mason Medical Center, Seattle, WA; Adam Dicker, Radiation Therapy Oncology Group, Philadelphia, PA; Jeff Isaacson, Clovis Oncology, Boulder, CO; Harpreet Wasan, Hammersmith Hospital, London; Lindsey Rolfe and Paramjit Kaur, Clovis Oncology UK, Cambridge; T.R. Jeffrey Evans, University of Glasgow, Glasgow, United Kingdom; Tone Ikdahl, Oslo Universitetssykehus, Oslo, Norway; Ihor Bondarenko, Dnipropetrovsk State Medical Academy, Dnipropetrovsk; Volodymyr Bondar, Donetsk Regional Antitumor Center, Donetsk, Ukraine; Irina Davidenko, Clinical Oncology Center 1, Krasnodar; August Garin, Blokhin Russian Cancer Research Center, Moscow, Russia; Stefan Boeck, Steffen Ormanns, and Volker Heinemann, Ludwig-Maximilians-University of Munich, Munich, Germany; Claudio Bassi, Ospedale Policlinico G.B. Rossi, Verona, Italy; and Roland Andersson, Lund University, Lund, Sweden.

Purpose: Gemcitabine requires transporter proteins to cross cell membranes. Low expression of human equilibrative nucleoside transporter-1 (hENT1) may result in gemcitabine resistance in pancreatic ductal adenocarcinoma (PDAC). CO-101, a lipid-drug conjugate of gemcitabine, was rationally designed to enter cells independently of hENT1. We conducted a randomized controlled trial to determine whether CO-101 improved survival versus gemcitabine in patients with metastatic PDAC (mPDAC) with low hENT1. The study also tested the hypothesis that gemcitabine is more active in patients with mPDAC tumors with high versus low hENT1 expression.

Patients And Methods: Patients were randomly assigned to CO-101 or gemcitabine, after providing a metastasis sample for blinded hENT1 assessment. An immunohistochemistry test measuring tumor hENT1 was developed. To dichotomize the population, an hENT1 cutoff value was defined using primary PDAC samples from an adjuvant trial, and a high/low cutoff was applied. The primary end point was overall survival (OS) in the low hENT1 subgroup.

Results: Of 367 patients enrolled, hENT1 status was measured in 358 patients (97.5%). Two hundred thirty-two (64.8%) of 358 patients were hENT1 low. There was no difference in OS between treatments in the low hENT1 subgroup or overall, with hazard ratios (HRs) of 0.994 (95% CI, 0.746 to 1.326) and 1.072 (95% CI, 0.856 to 1.344), respectively. The toxicity profiles in both arms were similar. Within the gemcitabine arm, there was no difference in survival between the high and low hENT1 subgroups (HR, 1.147; 95% CI, 0.809 to 1.626).

Conclusion: CO-101 is not superior to gemcitabine in patients with mPDAC and low tumor hENT1. Metastasis hENT1 expression did not predict gemcitabine outcome.
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December 2013

Randomized phase II trial of letrozole plus anti-MUC1 antibody AS1402 in hormone receptor-positive locally advanced or metastatic breast cancer.

Clin Cancer Res 2011 Nov 30;17(21):6822-30. Epub 2011 Aug 30.

Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.

Purpose: AS1402 is a humanized immunoglobulin G1 antibody that targets the aberrantly glycosylated antigen MUC1, which is overexpressed in 90% of breast tumors and contributes to estrogen-mediated growth and survival of breast cancer cells in vitro by modulating estrogen receptor (ER) activity. Aromatase inhibitors have been reported to enhance antibody-dependent cell-mediated cytotoxicity elicited by antibodies in vitro. We compared the outcomes of patients with breast cancer treated with letrozole with or without AS1402.

Experimental Design: The study population included 110 patients with locally advanced or metastatic hormone receptor-positive breast cancer randomized to receive 2.5 mg letrozole only once daily or with a weekly 9 mg/kg AS1402 infusion. The primary endpoint was overall response rate. Secondary endpoints included progression-free survival, time to progression, and safety. AS1402 exposure and influence of allotypes of FcγRIIIa, FcγRIIa, and MUC1 were evaluated.

Results: The study was stopped early because of a trend toward worse response rates and a higher rate of early disease progression in the AS1402 + letrozole arm. Final analysis revealed no significant difference in efficacy between the study arms. Evaluated gene polymorphisms did not define patient subgroups with improved outcomes. Addition of AS1402 to letrozole was associated with manageable toxicity.

Conclusions: Because adding AS1402 to letrozole did not improve outcomes compared with letrozole only, blocking ER may be a better strategy for harnessing MUC1 modulation of the ER to a clinical advantage. FcγRIIIa, FcγRIIa, and MUC1 allotype did not predict outcome for patients treated with letrozole with or without AS1402.
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November 2011