title: Phase I trial combining temozolomide plus lapatinib for the treatment of brain metastases in patients with HER2-positive metastatic breast cancer: the LAPTEM trial.
abstract: BACKGROUND
  Brain metastases (BMs) pose a clinical challenge in breast cancer (BC). Lapatinib or temozolomide showed activity in BM. Our study assessed the combination of both drugs as treatment for patients with HER2-positive BC and BM.
  
  
  METHODS
  Eighteen patients were enrolled, with sixteen of them having recurrent or progressive BM. Any type of previous therapy was allowed, and disease was assessed by gadolinium (Gd)-enhanced magnetic resonance imaging (MRI). The primary end points were the evaluation of the dose-limiting toxicities (DLTs) and the determination of the maximum-tolerated dose (MTD). The secondary end points included objective response rate, clinical benefit and duration of response.
  
  
  RESULTS
  The lapatinib-temozolomide regimen showed a favorable toxicity profile because the MTD could not be reached. The most common adverse events (AEs) were fatigue, diarrhea and constipation. Disease stabilization was achieved in 10 out of 15 assessable patients. The estimated median survival time for the 16 patients with BM reached 10.94 months (95% CI: 1.09-20.79), whereas the median progression-free survival time was 2.60 months [95% confidence interval (CI): 1.82-3.37].
  
  
  CONCLUSIONS
  The lapatinib-temozolomide combination is well tolerated. Preliminary evidence of clinical activity was observed in a heavily pretreated population, as indicated by the volumetric reductions occurring in brain lesions.
authors.affiliation: Breast Unit, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: E
authors.initials: E
authors.lastname: de Azambuja
authors.forename: D
authors.initials: D
authors.lastname: Zardavas
authors.forename: M
authors.initials: M
authors.lastname: Lemort
authors.forename: J
authors.initials: J
authors.lastname: Rossari
authors.forename: C
authors.initials: C
authors.lastname: Moulin
authors.forename: A
authors.initials: A
authors.lastname: Buttice
authors.forename: V
authors.initials: V
authors.lastname: D'Hondt
authors.forename: F
authors.initials: F
authors.lastname: Lebrun
authors.forename: Y
authors.initials: Y
authors.lastname: Lalami
authors.forename: F
authors.initials: F
authors.lastname: Cardoso
authors.forename: C
authors.initials: C
authors.lastname: Sotiriou
authors.forename: T
authors.initials: T
authors.lastname: Gil
authors.forename: D
authors.initials: D
authors.lastname: Devriendt
authors.forename: M
authors.initials: M
authors.lastname: Paesmans
authors.forename: M
authors.initials: M
authors.lastname: Piccart-Gebhart
authors.forename: A
authors.initials: A
authors.lastname: Awada
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality / Q000556:secondary; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D003606:Dacarbazine / Q000008:administration & dosage / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D000077341:Lapatinib; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D011799:Quinazolines / Q000008:administration & dosage; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D000077204:Temozolomide; D016896:Treatment Outcome
chemical_list: D003606:Dacarbazine; D000077341:Lapatinib; D011799:Quinazolines; D018719:Erb-b2 Receptor Tyrosine Kinases; D000077204:Temozolomide; C508053:ERBB2 protein, human
keywords: HER2; brain metastases; breast cancer; lapatinib; temozolomide