Abstract
Doxorubicin Transdrug (DT), a nanoformulation of doxorubicin, was demonstrated to overcome the chemoresistance of hepatocellular carcinoma (HCC) in preclinical models. Its efficacy and safety were thus investigated in phase I and randomised phase II trials in unresectable HCC. Phase I was a single dose of DT through the hepatic intra-arterial (HIA) route, dose-escalating 3+3 trial, evaluating five-dose levels from 10 to 40 mg/m2 with maximal tolerated dose (MTD) as primary endpoint. The multicentre phase II trial randomly assigned (2:1 ratio) patients to receive either 30 mg/m2 of DT through HIA route every 4 weeks for up to three courses or best standard of care (BSC). Progression-free survival (PFS) rate at 3 months was the primary endpoint. Overall survival (OS) and disease control rate (DCR) were secondary endpoints. In phase I, haematological and respiratory limited toxicities were reported at 35 and 40 mg/m2, giving MTD at 30 mg/m2. Partial response rate was 10%, and stable disease 70%. Phase II was discontinued due to three severe acute respiratory distress events in the DT group while 17 patients had received 30 mg/m2 DT and 11 BSC. At 3 months, PFS was 64% (95% CI 31 to 89) vs 75% (95% CI 35 to 97), and DCR 35% vs 27% ...Continue Reading
References
Aug 4, 1992·Biochemical Pharmacology·C CuvierM F Poupon
Aug 1, 1988·Cancer·C L LaiH J Lin
May 4, 1994·Journal of the National Cancer Institute·J G ParkM M Gottesman
Sep 13, 1994·Proceedings of the National Academy of Sciences of the United States of America·G J ZamanH J Broxterman
Jan 1, 1994·Cancer Chemotherapy and Pharmacology·A Colin de VerdièreP Couvreur
Jan 1, 1994·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·S BennisJ Robert
Jan 1, 1997·British Journal of Cancer·A C de VerdièreP Couvreur
Oct 11, 2001·Journal of Hepatology·J BruixUNKNOWN EASL Panel of Experts on HCC
Jun 7, 2002·Lancet·Josep M LlovetUNKNOWN Barcelona Liver Cancer Group
Sep 5, 2003·Annals of Oncology : Official Journal of the European Society for Medical Oncology·A Chanan-KhanF M Muggia
Apr 14, 2005·Journal of Hepatology·Luc BarraudLudmila Vitvitski
Sep 6, 2005·Toxicology·Janos Szebeni
May 25, 2007·The Oncologist·Heinz-Josef Lenz
Jul 20, 2007·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Robert G GishGerard T Kennealey
May 15, 2008·Journal of the National Cancer Institute·Josep M LlovetUNKNOWN Panel of Experts in HCC-Design Clinical Trials
Jul 25, 2008·The New England Journal of Medicine·Josep M LlovetUNKNOWN SHARP Investigators Study Group
Dec 20, 2008·The Lancet Oncology·Ann-Lii ChengZhongzhen Guan
Jun 28, 2011·Nanomedicine : Nanotechnology, Biology, and Medicine·János SzebeniYechezkel Barenholz
Aug 28, 2013·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Shukui QinYan Sun
Aug 28, 2013·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Josep M LlovetJoong-Won Park
Oct 2, 2013·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Ann-Lii ChengEric Raymond
Jul 25, 2014·JAMA : the Journal of the American Medical Association·Andrew X ZhuLi-Tzong Chen
Dec 31, 2014·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Andrew X ZhuYoon-Koo Kang
Dec 10, 2016·Lancet·Jordi BruixUNKNOWN RESORCE Investigators
Citations
May 8, 2018·Nanomaterials·Spiridon V SpirouOliviero L Gobbo
Feb 6, 2019·Journal of Drug Targeting·Simona MuraJulien Nicolas
Oct 11, 2019·Cancers·Sven H LoosenChristoph Roderburg
Nov 28, 2019·Expert Opinion on Drug Delivery·Giovanni TosiJörg Kreuter
Jun 25, 2019·ESMO Open·Christoph C Zielinski
Feb 7, 2020·International Journal of Molecular Sciences·Gabriel N A RegoLionel F Gamarra
Jun 6, 2018·Nanomaterials·Spiridon V SpirouClaudia Innocenti
Jan 4, 2020·Pharmaceutical Research·Christelle ZandanelChristine Vauthier
Mar 21, 2019·Journal of Drug Targeting·Christine Vauthier
Jun 20, 2020·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Roman KloecknerJordi Bruix
May 23, 2019·Cancer Immunology Research·Zhen TaoKe Chen
Dec 29, 2020·Journal of Controlled Release : Official Journal of the Controlled Release Society·Fatemeh ArasteMona Alibolandi
Feb 8, 2021·Ultrasound in Medicine & Biology·Sofie SnipstadSigrid Berg
Feb 23, 2021·Frontiers in Pharmacology·Agnese GagliardiDonato Cosco
May 25, 2021·Advanced Science·Weisen ZhangNicolas H Voelcker
Jul 19, 2021·Chemico-biological Interactions·Tatiana N PashirovaPatrick Masson
Aug 28, 2021·Biology·Giulio Eugenio VallatiPierleone Lucatelli
Oct 3, 2021·International Journal of Pharmaceutics·Christelle ZandanelChristine Vauthier