PMID- 24013582
OWN - NLM
STAT- MEDLINE
DCOM- 20140707
LR  - 20200206
IS  - 1569-8041 (Electronic)
IS  - 0923-7534 (Linking)
VI  - 24
IP  - 12
DP  - 2013 Dec
TI  - Phase I trial combining temozolomide plus lapatinib for the treatment of brain 
      metastases in patients with HER2-positive metastatic breast cancer: the LAPTEM 
      trial.
PG  - 2985-9
LID - 10.1093/annonc/mdt359 [doi]
AB  - 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.
FAU - de Azambuja, E
AU  - de Azambuja E
AD  - Breast Unit, Institut Jules Bordet, Universite Libre de Bruxelles, Brussels, 
      Belgium.
FAU - Zardavas, D
AU  - Zardavas D
FAU - Lemort, M
AU  - Lemort M
FAU - Rossari, J
AU  - Rossari J
FAU - Moulin, C
AU  - Moulin C
FAU - Buttice, A
AU  - Buttice A
FAU - D'Hondt, V
AU  - D'Hondt V
FAU - Lebrun, F
AU  - Lebrun F
FAU - Lalami, Y
AU  - Lalami Y
FAU - Cardoso, F
AU  - Cardoso F
FAU - Sotiriou, C
AU  - Sotiriou C
FAU - Gil, T
AU  - Gil T
FAU - Devriendt, D
AU  - Devriendt D
FAU - Paesmans, M
AU  - Paesmans M
FAU - Piccart-Gebhart, M
AU  - Piccart-Gebhart M
FAU - Awada, A
AU  - Awada A
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130907
PL  - England
TA  - Ann Oncol
JT  - Annals of oncology : official journal of the European Society for Medical 
      Oncology
JID - 9007735
RN  - 0 (Quinazolines)
RN  - 0VUA21238F (Lapatinib)
RN  - 7GR28W0FJI (Dacarbazine)
RN  - EC 2.7.10.1 (ERBB2 protein, human)
RN  - EC 2.7.10.1 (Receptor, ErbB-2)
RN  - YF1K15M17Y (Temozolomide)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Antineoplastic Combined Chemotherapy Protocols/pharmacology/*therapeutic use
MH  - Brain Neoplasms/*drug therapy/metabolism/mortality/secondary
MH  - Breast Neoplasms/*drug therapy/metabolism/mortality/pathology
MH  - Dacarbazine/administration & dosage/analogs & derivatives
MH  - Disease-Free Survival
MH  - Female
MH  - Humans
MH  - Lapatinib
MH  - Maximum Tolerated Dose
MH  - Middle Aged
MH  - Quinazolines/administration & dosage
MH  - Receptor, ErbB-2/*metabolism
MH  - Temozolomide
MH  - Treatment Outcome
OTO - NOTNLM
OT  - HER2
OT  - brain metastases
OT  - breast cancer
OT  - lapatinib
OT  - temozolomide
EDAT- 2013/09/10 06:00
MHDA- 2014/07/08 06:00
CRDT- 2013/09/10 06:00
PHST- 2013/09/10 06:00 [entrez]
PHST- 2013/09/10 06:00 [pubmed]
PHST- 2014/07/08 06:00 [medline]
AID - S0923-7534(19)36722-5 [pii]
AID - 10.1093/annonc/mdt359 [doi]
PST - ppublish
SO  - Ann Oncol. 2013 Dec;24(12):2985-9. doi: 10.1093/annonc/mdt359. Epub 2013 Sep 7.