title: Erlotinib and chemoradiation followed by maintenance erlotinib for locally advanced pancreatic cancer: a phase I study.
abstract: OBJECTIVE
  A phase I trial was conducted to determine the maximally tolerated dose of erlotinib with concurrent gemcitabine, paclitaxel, and radiation for patients with locally advanced pancreatic cancer and to gather preliminary data on maintenance erlotinib after chemoradiation.
  
  
  METHODS
  Patients received gemcitabine, 75 mg/m2, and paclitaxel, 40 mg/m, weekly for 6 weeks with 50.4 radiation to the primary tumor and draining lymph nodes with a 2- to 3-cm margin. Erlotinib was administered over 3-dose levels (50-100 mg/d) with chemoradiation then all patients received 150 mg/d maintenance until disease progression.
  
  
  RESULTS
  Seventeen patients were assessable for toxicity; 13 with locally advanced disease and 4 who had undergone resection but had positive margins. At erlotinib dosages > or =75 mg/d with chemoradiation the dose-limiting toxicities were diarrhea, dehydration, rash, myelosuppression, and small bowel stricture. Maintenance erlotinib, 150 mg/d, was well tolerated. The median survival of the 13 patients with locally advanced disease was 14.0 months and 6 of 13 (46%) had a partial response.
  
  
  CONCLUSIONS
  The maximum tolerated dose of erlotinib with gemcitabine, paclitaxel and concurrent radiation is 50 mg/d for patients with locally advanced pancreatic cancer. Full dose maintenance erlotinib is well tolerated. Promising preliminary activity and overall survival were demonstrated.
authors.affiliation: Brown University Oncology Group, Providence, RI, USA.
authors.forename: David
authors.initials: D
authors.lastname: Iannitti
authors.forename: Tom
authors.initials: T
authors.lastname: Dipetrillo
authors.forename: Paul
authors.initials: P
authors.lastname: Akerman
authors.forename: John Mark
authors.initials: JM
authors.lastname: Barnett
authors.forename: Christine
authors.initials: C
authors.lastname: Maia-Acuna
authors.forename: Dennis
authors.initials: D
authors.lastname: Cruff
authors.forename: Tom
authors.initials: T
authors.lastname: Miner
authors.forename: Diane
authors.initials: D
authors.lastname: Martel
authors.forename: William
authors.initials: W
authors.lastname: Cioffi
authors.forename: Melissa
authors.initials: M
authors.lastname: Remis
authors.forename: Teresa
authors.initials: T
authors.lastname: Kennedy
authors.forename: Howard
authors.initials: H
authors.lastname: Safran
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy / Q000601:surgery; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D000069347:Erlotinib Hydrochloride; D005260:Female; D005500:Follow-Up Studies; D005767:Gastrointestinal Diseases / Q000139:chemically induced; D006402:Hematologic Diseases / Q000139:chemically induced; D006801:Humans; D015993:Life Tables; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors; D017239:Paclitaxel / Q000008:administration & dosage; D010180:Pancreatectomy; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy / Q000601:surgery; D011799:Quinazolines / Q000008:administration & dosage / Q000009:adverse effects; D020266:Radiotherapy, Conformal; D016019:Survival Analysis; D016896:Treatment Outcome; D000093542:Gemcitabine
chemical_list: D009363:Neoplasm Proteins; D011799:Quinazolines; D003841:Deoxycytidine; D000069347:Erlotinib Hydrochloride; D066246:ErbB Receptors; D017239:Paclitaxel; D000093542:Gemcitabine