title: Neoadjuvant continuous infusion of weekly 5-fluorouracil and escalating doses of oxaliplatin plus concurrent radiation in locally advanced oesophageal squamous cell carcinoma: results of a phase I/II trial.
abstract: Oxaliplatin and 5-fluorouracil have a significant activity in locally advanced oesophageal squamous cell cancer (OSCC). However, their optimal dosage and efficacy when combined with concurrent radiotherapy as neoadjuvant treatment are unknown. This non-randomised, phase I/II study aimed to define the maximum tolerated dose (MTD) and assessed the histopathological tumour response rate to neoadjuvant oxaliplatin in weekly escalating doses (40, 45, 50 mg m(-2)) and continuous infusional 5-fluorouracil (CI-5FU; 225 mg m(-2)) plus concurrent radiotherapy. Patients had resectable OSCC. Resection was scheduled for 4-6 weeks after chemoradiotherapy. During phase I (dose escalation; n=19), weekly oxaliplatin 45 mg m(-2) plus CI-5FU 225 mg m(-2) was established as the MTD and was the recommended dosage for phase II. Oesophageal mucositis was the dose-limiting toxicity at higher doses. During phase II, histopathological responses (<10% residual tumour cells within the specimen) were observed in 10 of 16 patients (63%; 95% confidence interval: 39-82%). Overall, 16 of the 25 patients (64%) who underwent resection had a histopathological response; tumour-free resection (R0) was achieved in 80%. Neoadjuvant weekly oxaliplatin 45 mg m(-2) plus CI-5FU 225 mg m(-2) with concurrent radiotherapy provides promising histological response rates and R0 resection rates in locally advanced OSCC.
authors.affiliation: Third Department of Internal Medicine (Haematology/Medical Oncology), Klinikum rechts der Isar, Technical University of Munich, Munich, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Lorenzen
authors.forename: B
authors.initials: B
authors.lastname: Brücher
authors.forename: F
authors.initials: F
authors.lastname: Zimmermann
authors.forename: H
authors.initials: H
authors.lastname: Geinitz
authors.forename: J
authors.initials: J
authors.lastname: Riera
authors.forename: T
authors.initials: T
authors.lastname: Schuster
authors.forename: N
authors.initials: N
authors.lastname: Roethling
authors.forename: H
authors.initials: H
authors.lastname: Höfler
authors.forename: K
authors.initials: K
authors.lastname: Ott
authors.forename: C
authors.initials: C
authors.lastname: Peschel
authors.forename: J R
authors.initials: JR
authors.lastname: Siewert
authors.forename: M
authors.initials: M
authors.lastname: Molls
authors.forename: F
authors.initials: F
authors.lastname: Lordick
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000532:radiotherapy / Q000601:surgery / Q000628:therapy*; D017024:Chemotherapy, Adjuvant; D003131:Combined Modality Therapy; D004305:Dose-Response Relationship, Drug; D004938:Esophageal Neoplasms / Q000188:drug therapy / Q000532:radiotherapy / Q000601:surgery / Q000628:therapy*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D008297:Male; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D016896:Treatment Outcome
chemical_list: D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D005472:Fluorouracil
references.citation: Ann Surg. 2005 May;241(5):810-7; discussion 817-20
references.pmid: 15849517
references.citation: Int J Radiat Oncol Biol Phys. 2002 Mar 15;52(4):1092-8
references.pmid: 11958906
references.citation: J Clin Oncol. 2007 Aug 20;25(24):3719-25
references.pmid: 17704421
references.citation: Cancer. 2001 Jul 15;92(2):279-86
references.pmid: 11466680
references.citation: Br J Cancer. 2005 Jul 25;93(2):190-4
references.pmid: 16012522
references.citation: Control Clin Trials. 1996 Aug;17(4):343-6
references.pmid: 8889347
references.citation: Langenbecks Arch Chir. 1988;373(6):367-76
references.pmid: 3210852
references.citation: Ann Oncol. 2005 Dec;16(12):1898-905
references.pmid: 16219623
references.citation: Ann Surg. 2002 Sep;236(3):376-84; discussion 384-5
references.pmid: 12192324
references.citation: J Clin Oncol. 2000 Feb;18(4):868-76
references.pmid: 10673530
references.citation: Ann Oncol. 2005 Jul;16(7):1140-6
references.pmid: 15894548
references.citation: Br J Surg. 1998 Jun;85(6):840-4
references.pmid: 9667720
references.citation: J Clin Oncol. 1996 Jan;14(1):156-63
references.pmid: 8558191
references.citation: Lancet Oncol. 2007 Mar;8(3):226-34
references.pmid: 17329193
references.citation: J Chronic Dis. 1961 Apr;13:346-53
references.pmid: 13704181
references.citation: N Engl J Med. 1997 Jul 17;337(3):161-7
references.pmid: 9219702
references.citation: N Engl J Med. 1992 Jun 11;326(24):1593-8
references.pmid: 1584260
references.citation: Cancer. 2003 Oct 1;98(7):1521-30
references.pmid: 14508841
references.citation: J Clin Oncol. 2007 Sep 20;25(27):4217-23
references.pmid: 17548840
references.citation: J Clin Oncol. 2007 Apr 1;25(10):1160-8
references.pmid: 17401004
references.citation: Ann Surg Oncol. 2008 Jan;15(1):88-95
references.pmid: 17896144
references.citation: J Clin Oncol. 1996 Mar;14(3):829-37
references.pmid: 8622031
references.citation: Ann Thorac Surg. 2003 Jun;75(6):1720-6
references.pmid: 12822606
references.citation: J Clin Oncol. 2007 Jan 1;25(1):110-7
references.pmid: 17194912
references.citation: Clin Colorectal Cancer. 2002 May;2(1):24-30
references.pmid: 12453333
references.citation: Cancer J. 2003 Jul-Aug;9(4):251-60
references.pmid: 12967135
references.citation: Cancer. 2006 May 15;106(10):2119-27
references.pmid: 16607651
references.citation: N Engl J Med. 1996 Aug 15;335(7):462-7
references.pmid: 8672151
references.citation: J Clin Oncol. 2005 Apr 1;23(10):2310-7
references.pmid: 15800321
references.citation: Cancer. 2001 Apr 15;91(8):1574-8
references.pmid: 11301408
references.citation: J Clin Oncol. 1997 Jan;15(1):277-84
references.pmid: 8996153
references.citation: J Clin Oncol. 2008 Mar 1;26(7):1086-92
references.pmid: 18309943
references.citation: Oncology. 2003;64(3):280-7
references.pmid: 12697970
references.citation: J Clin Oncol. 2002 Jun 15;20(12):2844-50
references.pmid: 12065561