PMID- 26308485
OWN - NLM
STAT- MEDLINE
DCOM- 20160322
LR  - 20181113
IS  - 1097-0142 (Electronic)
IS  - 0008-543X (Print)
IS  - 0008-543X (Linking)
VI  - 121
IP  - 23
DP  - 2015 Dec 1
TI  - Multicenter phase 2 study of patupilone for recurrent or progressive brain 
      metastases from non-small cell lung cancer.
PG  - 4165-72
LID - 10.1002/cncr.29636 [doi]
AB  - BACKGROUND: Treatment options for patients with non-small cell lung cancer 
      (NSCLC) with brain metastases are limited. Patupilone (EPO906), a blood-brain 
      barrier-penetrating, microtubule-targeting, cytotoxic agent, has shown clinical 
      activity in phase 1/2 studies in patients with NSCLC. This study evaluates the 
      efficacy, pharmacokinetics, and safety of patupilone in NSCLC brain metastases. 
      METHODS: Adult patients with NSCLC and confirmed progressive brain metastases 
      received patupilone intravenously at 10 mg/m(2) every 3 weeks. The primary 
      endpoint of this multinomial 2-stage study combined early progression (EP; death 
      or progression within 3 weeks) and progression-free survival at 9 weeks (PFS9w) 
      to determine drug activity. RESULTS: Fifty patients with a median age of 60 years 
      (range, 33-74 years) were enrolled; the majority were men (58%), and most had 
      received prior therapy for brain metastases (98%). The PFS9w rate was 36%, and 
      the EP rate was 26%. Patupilone blood pharmacokinetic analyses showed mean areas 
      under the concentration-time curve from time zero to 504 hours for cycles 1 and 3 
      of 1544 and 1978 ng h/mL, respectively, and a mean steady state distribution 
      volume of 755 L/m(2) . Grade 3/4 adverse events (AEs), regardless of their 
      relation with the study drug, included diarrhea (24%), pulmonary embolisms (8%), 
      convulsions (4%), and peripheral neuropathy (4%). All patients discontinued the 
      study drug: 31 (62%) for disease progression and 13 (26%) for AEs. Twenty-five of 
      32 deaths were due to brain metastases. The median time to progression and the 
      overall survival were 3.2 and 8.8 months, respectively. CONCLUSIONS: This is the 
      first prospective study of chemotherapy for recurrent brain metastases from 
      NSCLC. In this population, patupilone demonstrated activity in heavily treated 
      patients.
CI  - (c) 2015 American Cancer Society.
FAU - Nayak, Lakshmi
AU  - Nayak L
AD  - Center For Neuro-Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
FAU - DeAngelis, Lisa M
AU  - DeAngelis LM
AD  - Department of Neurology, Memorial Sloan Kettering Cancer Center, New York, New 
      York.
FAU - Robins, H Ian
AU  - Robins HI
AD  - Department of Human Oncology, University of Wisconsin Hospital and Clinics, 
      Madison, Wisconsin.
FAU - Govindan, Ramaswamy
AU  - Govindan R
AD  - Division of Oncology, Washington University School of Medicine in St. Louis, St. 
      Louis, Missouri.
FAU - Gadgeel, Shirish
AU  - Gadgeel S
AD  - Karmanos Cancer Institute/Wayne State University, Detroit, Michigan.
FAU - Kelly, Karen
AU  - Kelly K
AD  - Division of Hematology and Oncology, Davis Comprehensive Cancer Center, 
      University of California, Sacramento, California.
FAU - Rigas, James R
AU  - Rigas JR
AD  - Norris Cotton Cancer Center/Dartmouth-Hitchcock Medical Center, Lebanon, New 
      Hampshire.
FAU - Peereboom, David M
AU  - Peereboom DM
AD  - Burkhardt Brain Tumor and Neuro-Oncology Center, Cleveland Clinic, Cleveland, 
      Ohio.
FAU - Rosenfeld, Steven S
AU  - Rosenfeld SS
AD  - Department of Neurology, Columbia University Medical Center/New York 
      Presbyterian, New York, New York.
FAU - Muzikansky, Alona
AU  - Muzikansky A
AD  - Biostatistics Center, Massachusetts General Hospital, Boston, Massachusetts.
FAU - Zheng, Ming
AU  - Zheng M
AD  - Novartis Pharmaceuticals Corporation, East Hanover, New Jersey.
FAU - Urban, Patrick
AU  - Urban P
AD  - Novartis Pharmaceuticals Corporation, East Hanover, New Jersey.
FAU - Abrey, Lauren E
AU  - Abrey LE
AD  - Department of Neurology, Memorial Sloan Kettering Cancer Center, New York, New 
      York.
FAU - Omuro, Antonio
AU  - Omuro A
AD  - Department of Neurology, Memorial Sloan Kettering Cancer Center, New York, New 
      York.
FAU - Wen, Patrick Y
AU  - Wen PY
AD  - Center For Neuro-Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
LA  - eng
GR  - P30 CA008748/CA/NCI NIH HHS/United States
GR  - U01 CA105663/CA/NCI NIH HHS/United States
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, Non-U.S. Gov't
DEP - 20150826
PL  - United States
TA  - Cancer
JT  - Cancer
JID - 0374236
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Epothilones)
RN  - UEC0H0URSE (epothilone B)
SB  - IM
MH  - Administration, Intravenous
MH  - Adult
MH  - Aged
MH  - Antineoplastic Agents/*administration & dosage/adverse effects
MH  - Brain Neoplasms/*drug therapy/mortality/*secondary
MH  - Carcinoma, Non-Small-Cell Lung/*drug therapy/mortality
MH  - Disease Progression
MH  - Drug Administration Schedule
MH  - Epothilones/*administration & dosage/adverse effects
MH  - Female
MH  - Humans
MH  - Lung Neoplasms/*drug therapy/mortality
MH  - Male
MH  - Middle Aged
MH  - Neoplasm Recurrence, Local/*drug therapy/mortality
MH  - Prospective Studies
MH  - Survival Analysis
MH  - Treatment Outcome
PMC - PMC5941922
MID - NIHMS814860
OTO - NOTNLM
OT  - brain metastases
OT  - chemotherapy
OT  - non-small cell lung cancer
OT  - patupilone
OT  - recurrent metastases
COIS- Conflict of interest(s): LN: Advisory board for Amgen LMD: Advisory board for 
      CarThera, Celgene RG: Consulting for Pfizer, Merck, Boehringer Ingelheim, Clovis 
      Oncology, Helsinn Healthcare, Genentech, Abbvie, GlaxoSmith Kline SG: Personal 
      compensation from Novartis (for activities outside of submitted work) HIR, KK, 
      JRR, SSR, AM: none DMP: Research funding from Novartis (for activities outside of 
      submitted work) MZ, PU: Employee of Novartis LEA: Employee of Roche AO: Advisory 
      Board for Novartis (for activities outside of submitted work) PYW: Research 
      support from Novartis for submitted work. Research support from AbbVie, Agios, 
      Angiochem, Astra Zeneca, Cubist, Exelixis, Genentech/Roche, GlaxoSmith Kine, 
      Karyopharm, Merck, Novartis, Sanofi-Aventis, Vascular Biogenics. Advisory Board 
      for AbbVie, Celldex,Genentech/Roche, Novocure, Sigma Tau, Midatech, Vascular 
      Biogenics. Speakers Bureau for Merck.
EDAT- 2015/08/27 06:00
MHDA- 2016/03/24 06:00
PMCR- 2018/05/09
CRDT- 2015/08/27 06:00
PHST- 2015/04/02 00:00 [received]
PHST- 2015/07/09 00:00 [revised]
PHST- 2015/07/13 00:00 [accepted]
PHST- 2015/08/27 06:00 [entrez]
PHST- 2015/08/27 06:00 [pubmed]
PHST- 2016/03/24 06:00 [medline]
PHST- 2018/05/09 00:00 [pmc-release]
AID - 10.1002/cncr.29636 [doi]
PST - ppublish
SO  - Cancer. 2015 Dec 1;121(23):4165-72. doi: 10.1002/cncr.29636. Epub 2015 Aug 26.