PMID- 23697602
OWN - NLM
STAT- MEDLINE
DCOM- 20140213
LR  - 20211021
IS  - 1549-490X (Electronic)
IS  - 1083-7159 (Print)
IS  - 1083-7159 (Linking)
VI  - 18
IP  - 6
DP  - 2013 Jun
TI  - An open-label safety study of lapatinib plus trastuzumab plus paclitaxel in 
      first-line HER2-positive metastatic breast cancer.
PG  - 661-6
LID - 10.1634/theoncologist.2012-0129 [doi]
AB  - BACKGROUND: Recent data support the hypothesis that combining lapatinib and 
      trastuzumab with taxane chemotherapy may offer added clinical benefit to patients 
      with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast 
      cancer (MBC). This study examined the safety of the triplet combination in 
      first-line HER2-positive MBC. PATIENTS AND METHODS: Patients were enrolled into 
      three sequential cohorts; the last two cohorts were added by protocol amendment 
      following review of safety data from cohort 1. Patients in cohort 1 received 
      lapatinib (1000 mg/day) plus paclitaxel (80 mg/m(2) per week, 3 of every 4 
      weeks); cohort 2 received lapatinib (1000 mg/day) plus paclitaxel (70 mg/m(2) per 
      week, 3 of every 4 weeks); and cohort 3 received lapatinib (750 mg/day) plus 
      paclitaxel (80 mg/m(2) per week, 3 of every 4 weeks). All received standard 
      trastuzumab dosing. The primary objective was assessment of dose-limiting 
      toxicities, safety, and tolerability of this combination. RESULTS: The most 
      frequent adverse events (AEs) for all cohorts were diarrhea (89%), rash (79%), 
      fatigue (73%), alopecia (63%), nausea (63%), and vomiting (40%). In cohorts 1 and 
      2, the incidence of grade 3 diarrhea was 62% and 50%, respectively; in cohort 3, 
      the incidence was 25% (with prophylactic loperamide). Dehydration was the most 
      frequent serious AE (10%). Across cohorts, overall response rate was 75%. 
      CONCLUSIONS: The dose-limiting toxicity of paclitaxel, trastuzumab, and lapatinib 
      in first-line HER2-positive MBC was diarrhea. Of the triplet combinations tested, 
      the cohort receiving 750 mg/day dose of lapatinib had the lowest incidence of 
      diarrhea; therefore, this dose should be used in further studies on the treatment 
      of MBC.
FAU - Esteva, Francisco J
AU  - Esteva FJ
AD  - Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer 
      Center, Houston, Texas 77030, USA. fjesteva@mdanderson.org
FAU - Franco, Sandra X
AU  - Franco SX
FAU - Hagan, Maura K
AU  - Hagan MK
FAU - Brewster, Abenaa M
AU  - Brewster AM
FAU - Somer, Robert A
AU  - Somer RA
FAU - Williams, Will
AU  - Williams W
FAU - Florance, Allison M
AU  - Florance AM
FAU - Turner, Simon
AU  - Turner S
FAU - Stein, Steven
AU  - Stein S
FAU - Perez, Alejandra
AU  - Perez A
LA  - eng
SI  - ClinicalTrials.gov/NCT00272987
PT  - Clinical Trial
PT  - Journal Article
DEP - 20130522
PL  - England
TA  - Oncologist
JT  - The oncologist
JID - 9607837
RN  - 0 (Antibodies, Monoclonal, Humanized)
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
MH  - Adult
MH  - Antibodies, Monoclonal, Humanized/*administration & dosage
MH  - Antineoplastic Combined Chemotherapy Protocols
MH  - Breast Neoplasms/*drug therapy/genetics/pathology
MH  - Drug Administration Schedule
MH  - Drug-Related Side Effects and Adverse Reactions/pathology
MH  - Female
MH  - Humans
MH  - Lapatinib
MH  - Middle Aged
MH  - Neoplasm Metastasis/*drug therapy/pathology
MH  - Paclitaxel/*administration & dosage
MH  - Quinazolines/*administration & dosage
MH  - Receptor, ErbB-2/genetics
MH  - Trastuzumab
PMC - PMC4063391
OTO - NOTNLM
OT  - Breast cancer
OT  - HER2
OT  - Lapatinib
OT  - Paclitaxel
OT  - Trastuzumab
COIS- Disclosures of potential conflicts of interest may be found at the end of this 
      article.
EDAT- 2013/05/24 06:00
MHDA- 2014/02/14 06:00
PMCR- 2014/06/01
CRDT- 2013/05/24 06:00
PHST- 2013/05/24 06:00 [entrez]
PHST- 2013/05/24 06:00 [pubmed]
PHST- 2014/02/14 06:00 [medline]
PHST- 2014/06/01 00:00 [pmc-release]
AID - theoncologist.2012-0129 [pii]
AID - 3827861 [pii]
AID - 10.1634/theoncologist.2012-0129 [doi]
PST - ppublish
SO  - Oncologist. 2013 Jun;18(6):661-6. doi: 10.1634/theoncologist.2012-0129. Epub 2013 
      May 22.