PMID- 28385537
OWN - NLM
STAT- MEDLINE
DCOM- 20180529
LR  - 20180713
IS  - 1938-0666 (Electronic)
IS  - 1526-8209 (Linking)
VI  - 17
IP  - 6
DP  - 2017 Oct
TI  - Phase I Trial of Everolimus and Capecitabine in Metastatic HER2(-) Breast Cancer.
PG  - 418-426
LID - S1526-8209(16)30410-4 [pii]
LID - 10.1016/j.clbc.2017.03.003 [doi]
AB  - BACKGROUND: The mammalian target of rapamycin (mTOR) pathway is a driver of 
      breast tumorigenesis. The mTOR inhibitor everolimus reverses antihormonal therapy 
      resistance and is an approved therapy for metastatic breast cancer. A synergistic 
      effect with fluoropyrimidine has been suggested. The present study evaluated the 
      safety and tolerability of an all-oral combination of everolimus and capecitabine 
      for metastatic breast cancer (MBC). PATIENTS AND METHODS: MBC patients naive to 
      capecitabine and mTOR inhibitors who had received </= 3 previous chemotherapy 
      regimens in the metastatic setting were eligible for the present study. The 
      patients were scheduled to receive capecitabine 825 mg/m(2) twice daily for 14 
      days in a 21-day cycle, combined with everolimus in 5 separate dose cohorts: 2.5 
      mg every other day, 2.5 mg daily, 5 mg daily, 7.5 mg daily, and 10 mg daily. A 
      3+3 design was used. The maximum tolerated dose was based on the dose-limiting 
      toxicity of everolimus plus capecitabine. RESULTS: A total of 18 patients were 
      enrolled in the present trial. The median age was 58 years. Most had received 
      previous anthracycline (83%) and taxane (94%) therapy. The maximum tolerated dose 
      was everolimus 7.5 mg daily and capecitabine 825 mg/m(2). The incidence of grade 
      3 events was low and mainly hematologic in nature. One incident each of grade 4 
      neutropenia, thrombocytopenia, hyperglycemia, and mucositis occurred. No grade 5 
      events occurred. The clinical benefit rate was 50%. The median progression-free 
      survival was 196 days, and the median overall survival was 569 days. CONCLUSION: 
      The all-oral regimen of everolimus with capecitabine is active and well 
      tolerated, with encouraging results for progression-free survival, overall 
      survival, and clinical benefit rate in patients with MBC.
CI  - Copyright (c) 2017 Elsevier Inc. All rights reserved.
FAU - Vidal, Gregory A
AU  - Vidal GA
AD  - Division of Oncology, Department of Internal Medicine, University of Tennessee 
      West Cancer Center, Germantown, TN. Electronic address: gvidal@westclinic.com.
FAU - Chen, Mary
AU  - Chen M
AD  - Division of Oncology, Stanford University School of Medicine, Stanford, CA.
FAU - Sheth, Shruti
AU  - Sheth S
AD  - Division of Oncology, Stanford University School of Medicine, Stanford, CA.
FAU - Svahn, Tiffany
AU  - Svahn T
AD  - Diablo Valley Oncology and Hematology Medical Group, Pleasant Hill, CA.
FAU - Guardino, Ellie
AU  - Guardino E
AD  - Division of Oncology, Stanford University School of Medicine, Stanford, CA.
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20170316
PL  - United States
TA  - Clin Breast Cancer
JT  - Clinical breast cancer
JID - 100898731
RN  - 6804DJ8Z9U (Capecitabine)
RN  - 9HW64Q8G6G (Everolimus)
SB  - IM
MH  - Administration, Oral
MH  - Adult
MH  - Aged
MH  - Antineoplastic Combined Chemotherapy Protocols/*administration & dosage/*adverse 
      effects
MH  - Breast Neoplasms/*drug therapy/mortality
MH  - Capecitabine/administration & dosage/adverse effects
MH  - Disease-Free Survival
MH  - Dose-Response Relationship, Drug
MH  - Everolimus/administration & dosage/adverse effects
MH  - Female
MH  - Humans
MH  - Maximum Tolerated Dose
MH  - Middle Aged
MH  - Treatment Outcome
OTO - NOTNLM
OT  - 5-FU
OT  - Metastatic breast cancer
OT  - Phase 1
OT  - Tolerable
OT  - mTOR inhibitor
EDAT- 2017/04/08 06:00
MHDA- 2018/05/31 06:00
CRDT- 2017/04/08 06:00
PHST- 2016/10/19 00:00 [received]
PHST- 2017/01/24 00:00 [revised]
PHST- 2017/03/02 00:00 [accepted]
PHST- 2017/04/08 06:00 [pubmed]
PHST- 2018/05/31 06:00 [medline]
PHST- 2017/04/08 06:00 [entrez]
AID - S1526-8209(16)30410-4 [pii]
AID - 10.1016/j.clbc.2017.03.003 [doi]
PST - ppublish
SO  - Clin Breast Cancer. 2017 Oct;17(6):418-426. doi: 10.1016/j.clbc.2017.03.003. Epub 
      2017 Mar 16.