title: A Phase I study of the combination of oxaliplatin/docetaxel and vandetanib for the treatment of advanced gastroesophageal cancer.
abstract: BACKGROUND
  This study aimed to assess the safety and tolerability of the multitargeted tyrosine kinase inhibitor, vandetanib (V), in combination with two chemotherapeutic agents, oxaliplatin (O) and docetaxel (D) in advanced gastroesophageal (GE) cancer.
  
  
  METHODS
  This was a Phase I study (NCT00732745) with a standard 3+3 dose escalation design. The primary aim was to determine the optimal dose of the combination of vandetanib and OD chemotherapy.
  
  
  RESULTS
  Initial treatment for the first cohort consisted of oxaliplatin at 100 mg/m2 on day 1, docetaxel at 35 mg/m2 on days 1 and 8 and vandetanib 100 mg PO daily of 21-day treatment cycles. As dose limiting toxicity (DLT) was reached in 2 out of 3 patients in cohort 1 (one grade 3 and one grade 4 diarrhea with dehydration), 6 patients were treated then at dose level -1 (O 80 mg/m2 on day 1, D 30 mg/m2 on days 1 and 8, V 100 mg PO daily days 1-21) in which no further DLTs were observed. This dose was established as maximum tolerated dose and is the recommended phase 2 dose. 8 out of 9 enrolled patients had adenocarcinoma. At dose level 1, 1 of the 3 patients had a documented partial response and 2 patients had stable disease. At dose level -1, 1 of 6 patients achieved a complete response, 2 of 6 patients had stable disease, and 3 of 6 patients had progressive disease.
  
  
  CONCLUSIONS
  Vandetanib added to oxaliplatin and docetaxel showed manageable toxicity and limited activity in advanced GE cancer.
authors.affiliation: University Hospitals, Seidman Cancer Center, Case Western Reserve University, Case Comprehensive Cancer Center, Cleveland, OH, USA, bh2376@columbia.edu.
authors.forename: Balazs
authors.initials: B
authors.lastname: Halmos
authors.forename: Yuxia
authors.initials: Y
authors.lastname: Jia
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Bokar
authors.forename: Pingfu
authors.initials: P
authors.lastname: Fu
authors.forename: David J
authors.initials: DJ
authors.lastname: Adelstein
authors.forename: Rosalyn
authors.initials: R
authors.lastname: Juergens
authors.forename: Mary Beth
authors.initials: MB
authors.lastname: Rodal
authors.forename: Afshin
authors.initials: A
authors.lastname: Dowlati
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D000077143:Docetaxel; D004305:Dose-Response Relationship, Drug; D005770:Gastrointestinal Neoplasms / Q000188:drug therapy*; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000009:adverse effects; D000077150:Oxaliplatin; D010880:Piperidines / Q000008:administration & dosage / Q000009:adverse effects; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects; D011799:Quinazolines / Q000008:administration & dosage / Q000009:adverse effects; D040262:Receptors, Vascular Endothelial Growth Factor / Q000037:antagonists & inhibitors; D043823:Taxoids / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D010880:Piperidines; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D043823:Taxoids; D000077150:Oxaliplatin; D000077143:Docetaxel; D040262:Receptors, Vascular Endothelial Growth Factor; C452423:vandetanib
references.citation: Lancet. 2010 Aug 28;376(9742):687-97
references.pmid: 20728210
references.citation: J Clin Oncol. 2006 Oct 20;24(30):4922-7
references.pmid: 17050876
references.citation: J Clin Oncol. 2008 Nov 20;26(33):5407-15
references.pmid: 18936474
references.citation: J Clin Oncol. 2007 Sep 20;25(27):4270-7
references.pmid: 17878479
references.citation: J Clin Oncol. 2011 Mar 1;29(7):868-74
references.pmid: 21189380
references.citation: Clin Cancer Res. 2003 Dec 15;9(17):6461-8
references.pmid: 14695149
references.citation: J Cell Physiol. 2006 Aug;208(2):344-53
references.pmid: 16688779
references.citation: Nat Rev Clin Oncol. 2011 Apr 05;8(8):492-503
references.pmid: 21468131
references.citation: N Engl J Med. 2003 Dec 4;349(23):2241-52
references.pmid: 14657432
references.citation: J Clin Oncol. 2005 Nov 20;23(33):8389-95
references.pmid: 16293869
references.citation: Gastrointest Cancer Res. 2008 Mar;2(2):85-92
references.pmid: 19259300
references.citation: J Thorac Oncol. 2006 Nov;1(9):1002-9
references.pmid: 17409986
references.citation: Head Neck. 2012 Nov;34(11):1517-23
references.pmid: 22180262
references.citation: Anticancer Res. 2003 Jan-Feb;23(1B):785-91
references.pmid: 12680184
references.citation: Ann Oncol. 2008 Jan;19(1):104-8
references.pmid: 17897959
references.citation: J Clin Oncol. 2010 Feb 10;28(5):767-72
references.pmid: 20065189
references.citation: Surgery. 2002 Dec;132(6):960-6; discussion 966-7
references.pmid: 12490842
references.citation: Lancet Oncol. 2010 Jul;11(7):619-26
references.pmid: 20570559
references.citation: J Clin Oncol. 2007 Aug 1;25(22):3210-6
references.pmid: 17664468
references.citation: J Clin Oncol. 2012 Jan 10;30(2):134-41
references.pmid: 22025146
references.citation: J Gastroenterol Hepatol. 2002 Feb;17 Suppl:S172-5
references.pmid: 12000603
references.citation: Am J Clin Oncol. 2007 Aug;30(4):346-9
references.pmid: 17762433
references.citation: Oncologist. 2011;16(6):844-58
references.pmid: 21632459
references.citation: J Clin Endocrinol Metab. 2010 Jun;95(6):2664-71
references.pmid: 20371662
references.citation: Nat Clin Pract Endocrinol Metab. 2006 Jan;2(1):42-52
references.pmid: 16932252
references.citation: J Clin Oncol. 2007 Aug 1;25(22):3205-9
references.pmid: 17664467
references.citation: Anticancer Res. 2012 Apr;32(4):1403-8
references.pmid: 22493377
references.citation: Invest New Drugs. 2012 Aug;30(4):1684-9
references.pmid: 21863238
references.citation: J Clin Oncol. 2011 Oct 20;29(30):3968-76
references.pmid: 21844504
references.citation: Nature. 2005 Dec 15;438(7070):967-74
references.pmid: 16355214
references.citation: Ann Oncol. 2002 Sep;13(9):1469-78
references.pmid: 12196374
references.citation: J Clin Oncol. 2009 Jul 1;27(19):e3-4
references.pmid: 19470917