title: Erlotinib plus gemcitabine in patients with unresectable pancreatic cancer and other solid tumors: phase IB trial.
abstract: OBJECTIVE
  The purpose of this phase IB trial was to evaluate the tolerability, pharmacokinetics and preliminary evidence of antitumor activity of erlotinib plus gemcitabine in patients with pancreatic cancer and other solid tumors.
  
  
  METHODS
  Patients included those with advanced pancreatic adenocarcinoma or other malignancies potentially responsive to gemcitabine. In the escalating phase of the trial, patients were enrolled in sequential cohorts using 100 or 150 mg oral daily dosing of erlotinib. Gemcitabine dose was 1,000 mg/m(2) weekly x 7 (first cycle), then weekly x 3, every 4 weeks.
  
  
  RESULTS
  Twenty-six patients completed at least one course on study. In Cohort IA, at the 100 mg/day dose of erlotinib, three patients have developed grade 3 transaminase elevations. After stricter inclusion criteria were adopted (Cohort IB), no additional events of grade 3 transaminase elevations were observed and the dose of erlotinib was escalated to 150 mg/day (Cohorts IB and IIB) without reaching dose-limiting toxicities. The most common toxicities included diarrhea, skin rash, fatigue and neutropenia. The pharmacokinetic analyses did not reveal any significant interactions between erlotinib and gemcitabine. Objective responses were seen in two patients: cholangiocarcinoma and pancreatic cancer. Patients with unresectable or metastatic pancreatic cancer (n = 15) had a median progression-free survival of 289 days, the estimated overall survival of 389 days (12.5 months), and a 1-year survival rate of 51%.
  
  
  CONCLUSIONS
  The 150 mg/day dose of erlotinib can be safely administered in combination with standard dose gemcitabine in selected patients with pancreatic cancer and other advanced solid tumors. Promising antitumor activity has been observed in patients with pancreatic cancer.
authors.affiliation: Arizona Cancer Center, University of Arizona, 1515 North Campbell Avenue, Tucson, AZ 85724, USA. tdragovich@azcc.arizona.edu
authors.forename: Tomislav
authors.initials: T
authors.lastname: Dragovich
authors.forename: Mark
authors.initials: M
authors.lastname: Huberman
authors.forename: Daniel D
authors.initials: DD
authors.lastname: Von Hoff
authors.forename: Eric K
authors.initials: EK
authors.lastname: Rowinsky
authors.forename: Paul
authors.initials: P
authors.lastname: Nadler
authors.forename: Debra
authors.initials: D
authors.lastname: Wood
authors.forename: Marta
authors.initials: M
authors.lastname: Hamilton
authors.forename: George
authors.initials: G
authors.lastname: Hage
authors.forename: Julie
authors.initials: J
authors.lastname: Wolf
authors.forename: Amita
authors.initials: A
authors.lastname: Patnaik
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality / Q000556:secondary; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000493:pharmacokinetics; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D019540:Area Under Curve; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D000069347:Erlotinib Hydrochloride; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics; D011799:Quinazolines / Q000008:administration & dosage / Q000493:pharmacokinetics; D015996:Survival Rate; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D003841:Deoxycytidine; D000069347:Erlotinib Hydrochloride; D000093542:Gemcitabine