PMID- 24248687
OWN - NLM
STAT- MEDLINE
DCOM- 20140224
LR  - 20211021
IS  - 1527-7755 (Electronic)
IS  - 0732-183X (Print)
IS  - 0732-183X (Linking)
VI  - 31
IP  - 36
DP  - 2013 Dec 20
TI  - Pattern of rash, diarrhea, and hepatic toxicities secondary to lapatinib and 
      their association with age and response to neoadjuvant therapy: analysis from the 
      NeoALTTO trial.
PG  - 4504-11
LID - 10.1200/JCO.2013.50.9448 [doi]
AB  - PURPOSE: We investigated the pattern of rash, diarrhea, and hepatic adverse 
      events (AEs) secondary to lapatinib and their association with age and pathologic 
      complete response (pCR) in the Neoadjuvant Lapatinib and/or Trastuzumab Treatment 
      Optimisation (NeoALLTO) phase III trial. PATIENTS AND METHODS: Patients with 
      HER2-positive early breast cancer were randomly assigned to receive lapatinib 
      (Arm A), trastuzumab (Arm B), or their combination (Arm C) for 6 weeks followed 
      by the addition of paclitaxel for 12 weeks before surgery. We investigated the 
      frequency and time to developing each AE according to age (</= 50 v > 50 years) and 
      their association with pCR in a logistic regression model adjusted for age, 
      hormone receptors, tumor size, nodal status, planned breast surgery, completion 
      of lapatinib administration, and treatment arm. RESULTS: Only patients randomly 
      assigned to arms A and C were eligible (n = 306). Younger patients (</= 50 years) 
      experienced significantly more rash compared with older patients (74.4% v 47.9%; 
      P < .0001). Diarrhea and hepatic AEs were observed in 78.8% and 41.2% of 
      patients, respectively, with no differences in rate or severity or time of onset 
      according to age. Early rash (ie, before starting paclitaxel) was independently 
      associated with a higher chance of pCR, mainly in patients older than 50 years 
      (odds ratio [OR] = 3.76; 95% CI, 1.69 to 8.34) but not in those </= 50 years (OR = 
      0.92; 95% CI, 0.45 to 1.88; P for interaction = .01). No significant association 
      was observed between pCR and diarrhea or hepatic AEs. CONCLUSION: Our results 
      indicate that the frequency and clinical relevance of lapatinib-related rash is 
      largely dependent on patient age.
FAU - Azim, Hatem A Jr
AU  - Azim HA Jr
AD  - Jose Baselga, Memorial Sloan-Kettering Cancer Center, NY; James G. Greger Jr, 
      GlaxoSmithKline, Collegeville, PA; Hatem A. Azim Jr, Martine Piccart, Evandro de 
      Azambuja, BrEAST Data Centre, Institut Jules Bordet, Universite Libre de 
      Bruxelles; Phuong Dinh, Breast International Group, Brussels; Peter Vuylsteke, 
      Sint-Elisabeth Hospital, Namur, Belgium; Dominique Agbor-tarh, Ian Bradbury, 
      Frontier Science, Kincraig, Kingussie, Scotland; Ian Smith, Royal Marsden 
      Hospital, and Institute of Cancer Research, London, United Kingdom; Serena Di 
      Cosimo, IRCCS Fondazione Instituto Nazionale dei Tumori, Milan, Italy; Serena Di 
      Cosimo, SOLTI Breast Cancer Research Group, Barcelona, Spain; Christian Jackisch, 
      Kilinikum Offenbach, Offenbach; Bahriye Aktas, Kliniken Essen-Mitte, Evang, 
      Essen; Holger Eidtmann, University Hospital Kiel, Kiel, Germany; Sung-Bae Kim, 
      Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea; 
      Chiun-Sheng Huang, National Taiwan University Hospital; Ruey Kuen Hsieh, Mackey 
      Memorial Hospital, Taipei, Taiwan; and Lydia Dreosti, University of Pretoria, 
      Pretoria, South Africa.
FAU - Agbor-Tarh, Dominique
AU  - Agbor-Tarh D
FAU - Bradbury, Ian
AU  - Bradbury I
FAU - Dinh, Phuong
AU  - Dinh P
FAU - Baselga, Jose
AU  - Baselga J
FAU - Di Cosimo, Serena
AU  - Di Cosimo S
FAU - Greger, James G Jr
AU  - Greger JG Jr
FAU - Smith, Ian
AU  - Smith I
FAU - Jackisch, Christian
AU  - Jackisch C
FAU - Kim, Sung-Bae
AU  - Kim SB
FAU - Aktas, Bahriye
AU  - Aktas B
FAU - Huang, Chiun-Sheng
AU  - Huang CS
FAU - Vuylsteke, Peter
AU  - Vuylsteke P
FAU - Hsieh, Ruey Kuen
AU  - Hsieh RK
FAU - Dreosti, Lydia
AU  - Dreosti L
FAU - Eidtmann, Holger
AU  - Eidtmann H
FAU - Piccart, Martine
AU  - Piccart M
FAU - de Azambuja, Evandro
AU  - de Azambuja E
LA  - eng
GR  - P30 CA008748/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20131118
PL  - United States
TA  - J Clin Oncol
JT  - Journal of clinical oncology : official journal of the American Society of 
      Clinical Oncology
JID - 8309333
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (Quinazolines)
RN  - 0VUA21238F (Lapatinib)
RN  - EC 2.7.10.1 (ERBB2 protein, human)
RN  - EC 2.7.10.1 (Receptor, ErbB-2)
RN  - P188ANX8CK (Trastuzumab)
RN  - P88XT4IS4D (Paclitaxel)
SB  - IM
EIN - J Clin Oncol. 2014 Feb 1;32(4):365
CIN - J Clin Oncol. 2014 Oct 20;32(30):3458-9. PMID: 25225430
CIN - J Clin Oncol. 2014 Oct 20;32(30):3459. PMID: 25225439
EIN - J Clin Oncol. 2018 Jan 1;36(1):98. PMID: 29281803
MH  - Adult
MH  - Age Factors
MH  - Aged
MH  - Antibodies, Monoclonal, Humanized/administration & dosage/*adverse effects
MH  - Antineoplastic Agents/administration & dosage/*adverse effects
MH  - Antineoplastic Combined Chemotherapy Protocols/adverse effects
MH  - Biomarkers, Tumor/analysis
MH  - Breast Neoplasms/chemistry/*drug therapy/pathology
MH  - Chemical and Drug Induced Liver Injury/*etiology
MH  - Chemotherapy, Adjuvant
MH  - Diarrhea/*chemically induced
MH  - Drug Administration Schedule
MH  - Drug Eruptions/*etiology
MH  - Female
MH  - Humans
MH  - Incidence
MH  - Lapatinib
MH  - Logistic Models
MH  - Middle Aged
MH  - Neoadjuvant Therapy/*methods
MH  - Paclitaxel/administration & dosage
MH  - Quinazolines/administration & dosage/*adverse effects
MH  - Receptor, ErbB-2/analysis
MH  - Time Factors
MH  - Trastuzumab
PMC - PMC5795667
COIS- Authors' disclosures of potential conflicts of interest and author contributions 
      are found at the end of this article.
EDAT- 2013/11/20 06:00
MHDA- 2014/02/25 06:00
PMCR- 2013/11/18
CRDT- 2013/11/20 06:00
PHST- 2013/11/20 06:00 [entrez]
PHST- 2013/11/20 06:00 [pubmed]
PHST- 2014/02/25 06:00 [medline]
PHST- 2013/11/18 00:00 [pmc-release]
AID - JCO.2013.50.9448 [pii]
AID - 09448 [pii]
AID - 10.1200/JCO.2013.50.9448 [doi]
PST - ppublish
SO  - J Clin Oncol. 2013 Dec 20;31(36):4504-11. doi: 10.1200/JCO.2013.50.9448. Epub 
      2013 Nov 18.