A phase I clinical and pharmacokinetic study of the multi-drug resistance protein-1 (MRP-1) inhibitor sulindac, in combination with epirubicin in patients with advanced cancer

Cancer Chemotherapy and Pharmacology
R O'ConnorJ Crown

Abstract

Multi-drug resistance mediated by ATP-binding cassette trans-membrane protein pumps is an important cause of cancer treatment failure. Sulindac has been shown to be a competitive substrate for the clinically important resistance protein, multi-drug resistance protein-1 (MRP-1), and thus might enhance the anti-cancer activity of substrate chemotherapeutic agents, e.g. anthracyclines. We conducted a dose-escalating, single arm, prospective, open label, non-randomised phase I trial of epirubicin (75 mg/m(2)) in combination with escalating oral doses of sulindac (0-800 mg) in patients with advanced cancer to identify an appropriate dose of sulindac to use in future resistance studies. Anthracycline and sulindac pharmacokinetics were studied in cycles 1 and 3. Seventeen patients (8 breast, 3 lung, 2 bowel, 1 melanoma, 1 renal, 1 ovarian and 1 of unknown primary origin, 16/17 having had prior chemotherapy) were enrolled. Eight patients received a full six cycles of treatment; 14 patients received three or more cycles. Dose-limiting toxicity was observed in two patients at 800 mg sulindac (1 renal impairment, 1 fatal haemoptysis in a patient with advanced lung cancer), and sulindac 600 mg was deemed to be the maximum tolerated dose. S...Continue Reading

References

Nov 11, 1976·Biochimica Et Biophysica Acta·R L Juliano, V Ling
Jan 1, 1992·Cancer Chemotherapy and Pharmacology·J R WadeB Whiting
Apr 1, 1981·The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society·S M HsuH Fanger
Jan 1, 1982·European Journal of Drug Metabolism and Pharmacokinetics·B VandelD Blum
Oct 1, 1982·Journal of Pharmacokinetics and Biopharmaceutics·K K Chan, M Gibaldi
Jun 1, 1994·Clinical Pharmacokinetics·J Robert
Jun 1, 1997·Clinical Pharmacokinetics·N M Davies, M S Watson
Dec 16, 1998·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·C P DuffyM Clynes
Jun 12, 1999·Biochemical and Biophysical Research Communications·A RollerM Weller
Jul 31, 1999·The Journal of Biological Chemistry·B D StrideR G Deeley
Nov 24, 1999·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·E H HermanV J Ferrans
Mar 31, 2000·Pharmacology & Therapeutics·A K LarsenA Skladanowski
Feb 21, 2002·World Journal of Gastroenterology : WJG·Y L WuJ Y Xu
Mar 26, 2003·Endocrine-related Cancer·F Leonessa, R Clarke
Apr 19, 2003·Cleveland Clinic Journal of Medicine·Carol A BurkeBret Lashner
Apr 25, 2003·Cancer Control : Journal of the Moffitt Cancer Center·Hilary Thomas, Helen M Coley
Sep 16, 2003·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Lajos PusztaiGabriel N Hortobagyi
Mar 17, 2004·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Peter L GreenbergJacob M Rowe
Sep 8, 2004·International Journal of Cancer. Journal International Du Cancer·Annemarie LarkinMartin Clynes
Feb 19, 2005·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Martin FilipitsRaimund Jakesz
Apr 23, 2005·Toxicology and Applied Pharmacology·Elaine M LeslieSusan P C Cole

❮ Previous
Next ❯

Citations

Jan 20, 2012·Chinese Journal of Cancer·Yue-Li SunZhe-Sheng Chen
Nov 22, 2007·Expert Opinion on Drug Metabolism & Toxicology·Robert O'ConnorLorraine O'Driscoll
Feb 6, 2008·Expert Opinion on Drug Metabolism & Toxicology·Suneet ShuklaSuresh V Ambudkar
Mar 29, 2014·Drug Metabolism Reviews·Tereza Kunická, Pavel Souček
Jan 6, 2012·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·V HanušováL Skálová
Jun 19, 2007·Biochimica Et Biophysica Acta·Jean-Pierre GilletJosé Remacle
Mar 25, 2017·Expert Opinion on Therapeutic Targets·Piyush BugdeYan Li
Jan 16, 2010·Nature Reviews. Cancer·Jamie I FletcherMurray D Norris
Dec 30, 2014·Cell Biochemistry and Biophysics·Haitao XuShulan Huang
Aug 18, 2009·The Oncologist·David S BossJan H M Schellens
Aug 30, 2016·World Journal of Gastroenterology : WJG·Tao HuChi Hin Cho
Jul 30, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Bruno M F GonçalvesMaria-José U Ferreira
Aug 12, 2010·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·V HanusováL Skálová
Aug 10, 2018·World Journal of Gastroenterology : WJG·Aleksandra Adamska, Marco Falasca
Apr 3, 2012·Drug Resistance Updates : Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy·Laleh Amiri-KordestaniSusan E Bates

❮ Previous
Next ❯

Related Concepts

Related Feeds

Antimicrobial Resistance (ASM)

Antimicrobial resistance poses a significant threat to the continued successful use of antimicrobial agents for the treatment of bacterial infections.

Antimicrobial Resistance

Antimicrobial resistance poses a significant threat to the continued successful use of antimicrobial agents for the treatment of bacterial infections.

Breast Cancer: Chemo-Resistance

Some cancers are difficult to treat and aggressive including the "triple-negative" breast cancer. This type of cancer is chemoresistant even before chemotherapy begins. Here are the latest discoveries chemo-resistance in breast cancer.

Related Papers

European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)
C P DuffyM Clynes
Cancer Metastasis Reviews
Robert W RobeySusan E Bates
© 2022 Meta ULC. All rights reserved