Journal Article


J Crown
M Clynes
D Fennelly
S Kennedy
A Larkin
L O'Driscoll
R D Arnold
D E Mager
P Kinsella
C D Collins
and 3 others



female antagonists inhibitors drug therapy anti inflammatory agents non steroidal platelet count pathology blood pharmacokinetics chemotherapy adjuvant male middle aged adverse effects aged drug resistance neoplasm antibiotics antineoplastic sulindac myocardium immunohistochemistry prospective studies dose response relationship drug drug resistance multiple epirubicin creatinine therapeutic use humans adult metabolism troponin neoplasms p glycoprotein drug effects

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. (2006)

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. Sulindac had no effect on epirubicin pharmacokinetics. Among 15 patients with evaluable tumour, two partial responses were seen (malignant melanoma and breast cancer). Four others had prolonged stable disease. Epirubicin 75 mg/m(2) and sulindac 600 mg are the recommended doses for phase II studies for these agents in combination.
Collections Ireland -> Dublin City University -> PubMed

Full list of authors on original publication

J Crown, M Clynes, D Fennelly, S Kennedy, A Larkin, L O'Driscoll, R D Arnold, D E Mager, P Kinsella, C D Collins and 3 others

Experts in our system

John Crown
Dublin City University
Total Publications: 104
Martin Clynes
Dublin City University
Total Publications: 232
Susan Kennedy
Dublin City University
Total Publications: 40
Annemarie Larkin
Dublin City University
Total Publications: 26
Lorraine O'Driscoll
Trinity College Dublin
Total Publications: 164