Journal of Clinical Oncology, 2006 ASCO Annual Meeting Proceedings (Post-Meeting Edition).
Vol 24, No 18S (June 20 Supplement), 2006: 14094
© 2006 American Society of Clinical Oncology

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Abstract

Phase 1 study of intra-arterial hepatic (IAH) delivery of doxorubicin-transdrug (DT) for patients with advanced hepatocellular carcinoma (HCC)

CHU de Lyon, Lyon, France; Centre Hospitalier Régional d’Orléans, Orleans, France; Hôpitaux Civils de Strasbourg, Strasbourg, France; CHU de Clermont-Ferrand, Clermont-Ferrand, France; Hôpital de la Pitié Salpétrière, Paris, France; Bioalliance Pharma, Paris, France

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Background: HCC is a highly chemoresistant due to MDR efflux pumps. DT is a newly cytotoxic chemotherapy composed of doxorubicin-loadded polyisohexylcyanoacrylate nanoparticles, allowing doxorubicin to overcome MDR pumps [Barraud, J Hepatol 2005; 42: 736]. Methods: 16 cirrhotic patients (pts) of Child-Pugh A with advanced HCC, transaminases/GGT <5N, platelets >100000/mm³, neutrophiles >1500/mm³, were enrolled in a multicentric noncontrolled study. A single IAH injection of 10, 20, 30, 35, or 40mg/m2 DT (respectively 3,3,4, and 3 pts) was performed, tolerance and efficacy being assessed 4 weeks later. Results: Grade 4 neutropenia (2pts at 40mg/m2) gave the Maximal Tolerated Dose. Grade 2–3 hypertransaminasemia (transient) occurred dose-independently. Two serious adverse events (SAE) were hypotension and acute respiratory distress syndrome. All adverse events (AE) (90% grade 1–2) occurring during injection were dose-independent, and completely and fastly recovered : cough (6pts), dyspnea (2pts), SaO2 decrease (2pts), tachycardia (2pts), bradycardia (2pts), hypotension (2pts). Anti-tumor efficacy of DT was evaluated by helicoidal CT-scan with contrast injection 4 weeks after injection : 3pts (20%) showed partial response with frank decrease of contrast enhancement at arterial perfusion, 8pts (50%) remained stable, and 5pts (30%) had progression. Conclusions: This phase 1 showed that a single IAH injection of DT was safe until 35 mg/m2 for Child-Pugh A patients with advanced HCC. This dosage will be retained for the phase 2 step comprising 3 injections at 4-week intervals which will aim at confirming the antitumour efficacy of DT for HCC.

Author Disclosure

Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bioalliance Pharma Bioalliance Pharma