title: Phase I study of continuous and intermittent schedules of lapatinib in combination with vinorelbine in solid tumors.
abstract: BACKGROUND
  Chemotherapy in combination with small-molecule epidermal growth factor receptor inhibitors has yielded inconsistent results. Based on preclinical models, we conducted a phase I trial of two schedules of lapatinib and vinorelbine.
  
  
  METHODS
  Patients had advanced solid tumors and up to two prior chemotherapeutic regimens. Patients were enrolled on two dose-escalating schedules of lapatinib, continuous (arm A) or intermittent (arm B), with vinorelbine on days 1, 8, and 15 of a 28-day cycle. Tumors from a subset of patients were evaluated for gene mutations and expression of targets of interest.
  
  
  RESULTS
  Fifty-one patients were treated. The most common grade 3/4 toxic effects included leukopenia, neutropenia, and fatigue. Dose-limiting toxic effects were grade 3 infection, febrile neutropenia, and diarrhea (arm A) and bone pain and fatigue (arm B). The maximum tolerated dose was vinorelbine 20 mg/m(2) weekly and lapatinib 1500 mg daily (arm A) and vinorelbine 25 mg/m(2) weekly and lapatinib 1500 mg intermittently (arm B). One patient on each arm had a complete response; both had human epidermal growth factor receptor 2-positive breast cancer. In a subset of patients, lack of tumor PTEN expression correlated with a shorter time to progression.
  
  
  CONCLUSIONS
  In an unselected population, two schedules of lapatinib and vinorelbine were feasible and well tolerated.
authors.affiliation: Department of Internal Medicine, University of California Davis, Sacramento, CA 95817, USA. helen.chew@ucdmc.ucdavis.edu
authors.forename: H K
authors.initials: HK
authors.lastname: Chew
authors.forename: G
authors.initials: G
authors.lastname: Somlo
authors.forename: P C
authors.initials: PC
authors.lastname: Mack
authors.forename: B
authors.initials: B
authors.lastname: Gitlitz
authors.forename: R
authors.initials: R
authors.lastname: Gandour-Edwards
authors.forename: S
authors.initials: S
authors.lastname: Christensen
authors.forename: H
authors.initials: H
authors.lastname: Linden
authors.forename: L J
authors.initials: LJ
authors.lastname: Solis
authors.forename: X
authors.initials: X
authors.lastname: Yang
authors.forename: A M
authors.initials: AM
authors.lastname: Davies
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D000077341:Lapatinib; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality; D008297:Male; D008875:Middle Aged; D051059:PTEN Phosphohydrolase / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality; D011799:Quinazolines / Q000008:administration & dosage; D016896:Treatment Outcome; D014747:Vinblastine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000077235:Vinorelbine
chemical_list: D011799:Quinazolines; D000077341:Lapatinib; D014747:Vinblastine; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human; D000077235:Vinorelbine