PMID- 23408298
OWN - NLM
STAT- MEDLINE
DCOM- 20130701
LR  - 20220415
IS  - 1097-0142 (Electronic)
IS  - 0008-543X (Print)
IS  - 0008-543X (Linking)
VI  - 119
IP  - 10
DP  - 2013 May 15
TI  - A phase 1 study of everolimus plus docetaxel plus cisplatin as induction 
      chemotherapy for patients with locally and/or regionally advanced head and neck 
      cancer.
PG  - 1823-31
LID - 10.1002/cncr.27986 [doi]
AB  - BACKGROUND: Activation of the phosphatidylinositol-3-kinase (PI3K)/Akt/mammalian 
      target of rapamycin (mTOR) pathway is common in head and neck cancers, and it has 
      been demonstrated that inhibition of mTOR complex 1 sensitizes cell lines to 
      platinum and taxane chemotherapy. The authors conducted a phase 1 study to 
      evaluate the addition of oral everolimus to cisplatin and docetaxel as induction 
      chemotherapy for head and neck cancer. METHODS: In this single-institution phase 
      1 study, 3 doses of daily everolimus were explored: 5 mg daily, 7.5 mg daily 
      (administered as 5 mg daily alternating with 10 mg daily), and 10 mg daily of 
      each 21-day cycle. Cisplatin and docetaxel doses were fixed (both were 75 mg/m(2) 
      on day 1 of 21-day cycle) at each dose level with pegfilgrastim support. A 
      standard 3 + 3 dose-escalation plan was used. After induction, patients were 
      removed from protocol. RESULTS: Eighteen patients were enrolled (15 men, 3 
      women), and their median Karnofsky performance status was 90. The most common 
      toxicities were hyperglycemia, low hemoglobin, fatigue, and thrombocytopenia. 
      Dose-limiting toxicities (DLTs) were neutropenic fever (1 event at dose level 2, 
      2 events at dose level 3), and all patients recovered fully from these DLTs. The 
      maximum tolerated dose was exceeded at dose level 3. The progression-free 
      survival rate at 1 year was 87.5% (95% confidence interval, 56.8%-96.7%); and, at 
      2 years, it was 76.6% (95% confidence interval, 41.2%-92.3%). Activating PI3K 
      catalytic subunit alpha (PIK3CA) gene mutations were identified in 2 human 
      papillomavirus-associated oropharyngeal cancers. CONCLUSIONS: The phase 2 
      recommended dose was 7.5 mg daily for everolimus plus cisplatin and docetaxel 
      (both at 75 mg/m(2) on day 1 of a 21-day cycle) given with pegfilgrastim support.
CI  - Copyright (c) 2013 American Cancer Society.
FAU - Fury, Matthew G
AU  - Fury MG
AD  - Department of Medicine, Memorial Sloan-Kettering Cancer Center and Weill Cornell 
      Medical College, New York, NY, USA.
FAU - Sherman, Eric
AU  - Sherman E
FAU - Ho, Alan L
AU  - Ho AL
FAU - Xiao, Han
AU  - Xiao H
FAU - Tsai, Frank
AU  - Tsai F
FAU - Nwankwo, Oby
AU  - Nwankwo O
FAU - Sima, Camelia
AU  - Sima C
FAU - Heguy, Adrian
AU  - Heguy A
FAU - Katabi, Nora
AU  - Katabi N
FAU - Haque, Sofia
AU  - Haque S
FAU - Pfister, David G
AU  - Pfister DG
LA  - eng
GR  - P30 CA008748/CA/NCI NIH HHS/United States
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130213
PL  - United States
TA  - Cancer
JT  - Cancer
JID - 0374236
RN  - 0 (Taxoids)
RN  - 15H5577CQD (Docetaxel)
RN  - 9HW64Q8G6G (Everolimus)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - Q20Q21Q62J (Cisplatin)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Antineoplastic Combined Chemotherapy Protocols/adverse effects/*therapeutic use
MH  - Cisplatin/administration & dosage
MH  - Disease-Free Survival
MH  - Docetaxel
MH  - Drug Administration Schedule
MH  - Everolimus
MH  - Female
MH  - Head and Neck Neoplasms/*drug therapy/metabolism/*pathology
MH  - Humans
MH  - Induction Chemotherapy/adverse effects/*methods
MH  - Male
MH  - Maximum Tolerated Dose
MH  - Middle Aged
MH  - Mutation
MH  - Neoplasm Staging
MH  - Papillomavirus Infections/complications
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Risk Assessment
MH  - Risk Factors
MH  - Signal Transduction/drug effects
MH  - Sirolimus/administration & dosage/analogs & derivatives
MH  - Smoking/adverse effects
MH  - TOR Serine-Threonine Kinases/metabolism
MH  - Taxoids/administration & dosage
MH  - Treatment Outcome
PMC - PMC3969235
MID - NIHMS550926
COIS- CONFLICT OF INTEREST DISCLOSURES Dr. Matthew G. Fury and Dr. Alan L. Ho have 
      served on advisory boards for Novartis, the funding entity for this study.
EDAT- 2013/02/15 06:00
MHDA- 2013/07/03 06:00
PMCR- 2014/03/28
CRDT- 2013/02/15 06:00
PHST- 2012/09/29 00:00 [received]
PHST- 2012/12/21 00:00 [revised]
PHST- 2013/01/04 00:00 [accepted]
PHST- 2013/02/15 06:00 [entrez]
PHST- 2013/02/15 06:00 [pubmed]
PHST- 2013/07/03 06:00 [medline]
PHST- 2014/03/28 00:00 [pmc-release]
AID - 10.1002/cncr.27986 [doi]
PST - ppublish
SO  - Cancer. 2013 May 15;119(10):1823-31. doi: 10.1002/cncr.27986. Epub 2013 Feb 13.