title: Epidermal growth factor receptor tyrosine kinase inhibitor, erlotinib, and concurrent 5-fluorouracil, cisplatin and radiotherapy for patients with esophageal cancer: a phase I study.
abstract: This phase I trial investigates the safety of combining radiation, 5-fluorouracil (5-FU) and cisplatin with the epidermal growth factor receptor tyrosine kinase inhibitor, erlotinib, in patients with esophageal carcinoma. From April 2000 to January 2005, 11 patients with squamous or adenocarcinoma of the esophagus were enrolled. Patients received either 50, 100 or 150 mg oral erlotinib/day beginning on the first day of radiation (three patients in each dose cohort). Concurrent cisplatin (75 mg/m2 i.v., days 8 and 36) and 5-FU (1000 mg/m2 i.v., days 8-11 and 36-39) were also given with 50.4 Gy thoracic radiation, delivered at 180 cGy/day, 5 days/week. Toxicity was evaluated using the National Cancer Institute Common Toxicity Criteria (version 3.0). Erlotinib with concurrent 5-FU, cisplatin and thoracic radiation was well-tolerated at 50, 100 and 150 mg/day. The major toxicities were diarrhea (grade 1=18%, grade 2=18%), skin rash (grade 4=54.5%), nausea (grade 1=18%, grade 2=54%, grade 3=9%) and dehydration (grade 3=27%). All patients experienced esophagitis during treatment (grade 1=55%, grade 2=32%, grade 3=9%, grade 4=9%). Two patients were discontinued from the study secondary to non-erlotinib-related toxicities. We conclude that the phase I study demonstrates the safety and tolerability of erlotinib delivered at 150 mg/day with concurrent 5-FU, cisplatin and thoracic radiation. The major toxicities encountered were grade 1-2 diarrhea, grade 1 skin rash, grade 1-3 nausea and grade 3 dehydration. A phase II study is planned.
authors.affiliation: University of Alabama at Birmingham, Alabama 35249-6832, USA.
authors.forename: Michael C
authors.initials: MC
authors.lastname: Dobelbower
authors.forename: Suzanne M
authors.initials: SM
authors.lastname: Russo
authors.forename: Kevin P
authors.initials: KP
authors.lastname: Raisch
authors.forename: Leisa L
authors.initials: LL
authors.lastname: Seay
authors.forename: Lisa K
authors.initials: LK
authors.lastname: Clemons
authors.forename: Susan
authors.initials: S
authors.lastname: Suter
authors.forename: James
authors.initials: J
authors.lastname: Posey
authors.forename: James A
authors.initials: JA
authors.lastname: Bonner
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000532:radiotherapy; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000532:radiotherapy; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D000069347:Erlotinib Hydrochloride; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D008297:Male; D008875:Middle Aged; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011799:Quinazolines / Q000008:administration & dosage
chemical_list: D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D000069347:Erlotinib Hydrochloride; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases; D002945:Cisplatin; D005472:Fluorouracil