Abstract
Proper administration timing, dose-intensity, efficacy/toxicity ratio of triplet docetaxel (DTX), 5-fluorouracil (5-FU), and oxaliplatin (OXP) should be improved to safely perform three-drugs intensive first line in advanced gastric cancer (GC). This dose-finding study investigated recommended 5-FU and OXP doses, safety of triplet regimen and preliminary activity. Schedule: 12h-timed-flat-infusion 5-FU 700-1000 mg/m2/d 1-2, 8-9, 15-16, 22-23, with 100 mg/m2/d increase for dose level; DTX 50 mg/m2 d 1, 15 fixed dose, OXP at three increasing dose-levels 60-70-80 mg/m2 d 8, 22, every 4 weeks. Intra- and inter-patients dose-escalation was planned. Ten fit <75 years patients were enrolled: median age 59; young-elderly 4 (40%). From first to fifth dose level, 5 patients (1 per cohort) were enrolled according to intra-patient dose escalation, no dose-limiting toxicity (DLT) were reported. At sixth level, 1 DLT, G2 diarrhea, was reported, thus other 2 patients were enrolled, DLT 1/3 patients (33%). Maximum tolerated dose (MTD) was not reached. 5-FU and OXP recommended doses (RD) were 1000 mg/m2/d and 80 mg/m2, respectively. To confirm RD, other 3 patients were enrolled, without DLT. Cumulative G3-4 toxicities were: neutropenia 50%, leu...Continue Reading
References
Mar 1, 1989·Controlled Clinical Trials·R Simon
Jan 1, 1997·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·A WebbM Meehan
Aug 6, 1997·Journal of the National Cancer Institute·R SimonM C Christian
Apr 29, 1998·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·M ExtermannL Balducci
Feb 3, 2000·Journal of the National Cancer Institute·P TherasseS G Gwyther
Apr 17, 2002·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·P RossA Norman
Nov 28, 2002·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·C LouvetA de Gramont
Dec 1, 2005·American Journal of Clinical Oncology·Francesco GiulianiUNKNOWN Gruppo Oncologico dell' Italia Meridionale (prot. 2106)
Feb 1, 2006·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Jaffer A AjaniDirk Strumberg
Nov 1, 2006·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Eric Van CutsemUNKNOWN V325 Study Group
Nov 30, 2006·Cancer·Heinz-Joseph LenzJaffer A Ajani
Aug 1, 2007·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Arnaud D RothUNKNOWN Swiss Group for Clinical Cancer Research
Jan 4, 2008·The New England Journal of Medicine·David CunninghamUNKNOWN Upper Gastrointestinal Clinical Studies Group of the National Cancer Research Institute of the United Kingdom
Feb 20, 2008·The Lancet Oncology·Wasaburo KoizumiMasahiro Takeuchi
Mar 20, 2008·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Salah-Eddin Al-BatranUNKNOWN Arbeitsgemeinschaft Internistische Onkologie
Jun 19, 2008·Annals of Oncology : Official Journal of the European Society for Medical Oncology·M DankR Bugat
Aug 2, 2008·Annals of Oncology : Official Journal of the European Society for Medical Oncology·S-E Al-BatranE Jäger
Dec 24, 2008·Cancer Chemotherapy and Pharmacology·Alexandra LearyJ Oates
Jan 21, 2009·Annals of Oncology : Official Journal of the European Society for Medical Oncology·Y-K KangP I McCloud
May 29, 2009·Annals of Oncology : Official Journal of the European Society for Medical Oncology·A F C OkinesD Cunningham
Jul 17, 2009·Annals of Oncology : Official Journal of the European Society for Medical Oncology·M MoehlerUNKNOWN Arbeitsgemeinschaft Internistische Onkologie, Germany
Feb 18, 2010·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Jaffer A AjaniSilvia Falcon
Apr 30, 2010·Oncology Reports·M F MorelliC Ficorella
Aug 24, 2010·Lancet·Yung-Jue BangUNKNOWN ToGA Trial Investigators
Oct 21, 2010·BMC Cancer·Gemma BrueraEnrico Ricevuto
Jan 29, 2011·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Eliza HawkesDavid Cunningham
May 7, 2011·Expert Opinion on Biological Therapy·Gemma Bruera, Enrico Ricevuto
Jan 18, 2012·Neoplasma·A InalA Isikdogan
Jun 15, 2012·Clinical Colorectal Cancer·Corrado FicorellaEnrico Ricevuto
Aug 1, 2013·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·J A AjaniV Moiseyenko
Oct 8, 2013·Lancet·Charles S FuchsUNKNOWN REGARD Trial Investigators
Nov 6, 2013·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Shuichi HironakaIchinosuke Hyodo
Dec 7, 2013·BioMed Research International·Gemma BrueraEnrico Ricevuto
Dec 10, 2013·Gastric Cancer : Official Journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association·Luigi Di LauroMarcello Maugeri-Saccà
Dec 18, 2013·Journal of Experimental & Clinical Cancer Research : CR·Marcello Maugeri-SaccàLuigi Di Lauro
Sep 23, 2014·The Lancet Oncology·Hansjochen WilkeUNKNOWN RAINBOW Study Group
Oct 8, 2014·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Rosine GuimbaudOlivier Bouché
Nov 25, 2014·Annals of Oncology : Official Journal of the European Society for Medical Oncology·E Van CutsemP Rougier
Oct 7, 2015·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Manish A ShahDavid P Kelsen
Jan 6, 2017·Oncotarget·Gemma BrueraEnrico Ricevuto
Jan 1, 2015·Annals of Oncology : Official Journal of the European Society for Medical Oncology·E Van CutsemP Rougier