title: Phase I pilot study of oxaliplatin, infusional 5-FU, and cetuximab in recurrent or metastatic head and neck cancer.
abstract: Platinum-based therapy is active in advanced head and neck squamous cell carcinoma (HNSCC). Patients with inoperable recurrent or metastatic HNSCC have a poor prognosis; many have difficulty tolerating cisplatin-based regimens. Oxaliplatin has antitumor activity without many of the toxicities of cisplatin. We conducted a phase I pilot study to investigate the dose limitation of oxaliplatin with 5-fluorouracil (5-FU) and cetuximab in patients with untreated recurrent or metastatic HNSCC. The planned dose escalation schedule included: dose level 1: oxaliplatin 100 mg/m(2) day 1, 5-FU CIV 750 mg/m(2)/day over 96 h beginning day 1, and cetuximab 400 mg/m(2) day 1 (then 250 mg/m(2) weekly) every 21 days. Dose level 2: oxaliplatin 130 mg/m(2) day 1, 5-FU CIV 1,000 mg/m(2)/day over 96 h beginning day 1, and the same dose and schedule of cetuximab. Seven patients were accrued at dose level 1 and three at dose level 2. Dose level 1 toxicity included grade 1-2 stomatitis, fatigue, acneiform rash, and anemia, and grade 1 nausea and transaminitis. Dose level 2 toxicity was unacceptable: 2 of 3 patients experienced grade 4 toxicities (stomatitis, diarrhea, and acute renal failure) requiring hospitalization with one treatment-related death. Accrual was therefore closed with dose level 1 considered the maximum tolerated dose. Observed responses were short-lived. The regimen of oxaliplatin 100 mg/m(2) day 1, infusional 5-FU 750 mg/m(2)/day over 96 h beginning day 1, and cetuximab 400 mg/m(2) day 1 (then 250 mg/m(2) weekly), every 21 days, has manageable toxicity; these doses are recommended for phase II evaluation in the treatment for unresectable or metastatic HNSCC.
authors.affiliation: Edward Hines, Jr. VA Hospital, Hines, IL 60411, USA. jclark@lumc.edu
authors.forename: Joseph I
authors.initials: JI
authors.lastname: Clark
authors.forename: Joshua B
authors.initials: JB
authors.lastname: Greene
authors.forename: Ann
authors.initials: A
authors.lastname: Lau Clark
authors.forename: Jay S
authors.initials: JS
authors.lastname: Dalal
authors.forename: Craig C
authors.initials: CC
authors.lastname: Hofmeister
mesh_terms: D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy*; D000068818:Cetuximab; D004305:Dose-Response Relationship, Drug; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D006258:Head and Neck Neoplasms / Q000188:drug therapy*; D006801:Humans; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000009:adverse effects; D000077150:Oxaliplatin; D010865:Pilot Projects
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D000068818:Cetuximab; D005472:Fluorouracil