title: A phase I/II trial of trastuzumab plus erlotinib in metastatic HER2-positive breast cancer: a dual ErbB targeted approach.
abstract: BACKGROUND
  This phase I/II trial was conducted to determine the toxicities, recommended dose, pharmacokinetics, and response rate of erlotinib plus trastuzumab in metastatic HER2+ breast cancer.
  
  
  METHODS
  In phase I, sequential groups of patients with unlimited previous treatment received erlotinib at dose levels of 50, 100, and 150 mg plus standard dose weekly trastuzumab. In phase II, only patients with no previous chemotherapy or trastuzumab in the metastatic setting were allowed.
  
  
  RESULTS
  The combination was well tolerated among the 16 patients enrolled in phase I, and the recommended phase II dose of erlotinib was initially set at 150 mg. After an interim review of the first 8 patients in phase II revealed a higher incidence of rash and diarrhea than expected from the phase I experience, the protocol was amended to treat new phase II patients at erlotinib 100 mg, with the opportunity to escalate to 150 mg after 3 weeks, based on individual patient tolerability. As a result of advances in other therapies aimed at HER2+ breast cancer, phase II closed before meeting its accrual goal. Among the 12 evaluable chemotherapy- and trastuzumab-naive patients treated at the recommended phase II dose level, there were 4 partial responses, and the time to progression was 9.03 months (95% CI, 1.2-undetermined). No pharmacokinetic interaction between the 2 agents was observed.
  
  
  CONCLUSIONS
  The combination of erlotinib and trastuzumab was well tolerated when the dose of erlotinib was tailored to individual patient experience, and there was preliminary evidence of anticancer activity.
authors.affiliation: Department of Medicine, University of California, Los Angeles, CA, USA. cbritten@mednet.ucla.edu
authors.forename: Carolyn D
authors.initials: CD
authors.lastname: Britten
authors.forename: Richard S
authors.initials: RS
authors.lastname: Finn
authors.forename: Linda D
authors.initials: LD
authors.lastname: Bosserman
authors.forename: Steven G
authors.initials: SG
authors.lastname: Wong
authors.forename: Michael F
authors.initials: MF
authors.lastname: Press
authors.forename: Mubashira
authors.initials: M
authors.lastname: Malik
authors.forename: Bert L
authors.initials: BL
authors.lastname: Lum
authors.forename: Dennis J
authors.initials: DJ
authors.lastname: Slamon
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D000069347:Erlotinib Hydrochloride; D005260:Female; D006801:Humans; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D011379:Prognosis; D011799:Quinazolines / Q000008:administration & dosage; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D015996:Survival Rate; D014018:Tissue Distribution; D000068878:Trastuzumab; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D014408:Biomarkers, Tumor; D000069347:Erlotinib Hydrochloride; D011799:Quinazolines; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab