PMID- 20444843
OWN - NLM
STAT- MEDLINE
DCOM- 20110217
LR  - 20200626
IS  - 1569-8041 (Electronic)
IS  - 0923-7534 (Linking)
VI  - 21
IP  - 11
DP  - 2010 Nov
TI  - Erlotinib in combination with pemetrexed for patients with advanced 
      non-small-cell lung cancer (NSCLC): a phase I dose-finding study.
PG  - 2233-2239
LID - S0923-7534(19)39547-X [pii]
LID - 10.1093/annonc/mdq246 [doi]
AB  - BACKGROUND: Erlotinib and pemetrexed are approved single agents for second-line 
      treatment of non-small-cell lung cancer (NSCLC) and, in combination, have shown 
      synergistic antitumor activity in NSCLC cell lines. We investigated the safety, 
      pharmacokinetics and preliminary efficacy of combined erlotinib-pemetrexed in 
      patients with refractory advanced NSCLC. PATIENTS AND METHODS: A nonrandomized, 
      open-label, phase IB study was performed in patients with advanced NSCLC whose 
      disease had progressed on or following first-line chemotherapy with a 
      platinum-containing regimen or for whom the erlotinib-pemetrexed combination was 
      considered appropriate. Patients received i.v. pemetrexed 500-700 mg/m(2) every 3 
      weeks and oral erlotinib 100-150 mg/day. RESULTS: Twenty patients were recruited. 
      The most common adverse events (AEs) were rash, diarrhea and fatigue. Serious AEs 
      occurred in eight patients (three treatment related) and there were eight deaths 
      (none treatment related). Dose-limiting toxic effects were not experienced up to 
      erlotinib 150 mg/day plus pemetrexed 600 mg/m(2). Concurrent administration did not 
      affect pharmacokinetic parameters. Two patients achieved partial responses and 
      nine had stable disease. CONCLUSIONS: Erlotinib-pemetrexed combination is well 
      tolerated at doses equal to the licensed single-agent doses (150 mg/day and 500 
      mg/m(2), respectively). The good tolerability profile and promising efficacy 
      indicate that this combination warrants further investigation for patients with 
      advanced NSCLC.
FAU - Ranson, M
AU  - Ranson M
AD  - Department of Medical Oncology, University of Manchester, Christie Hospital, 
      Manchester, UK. Electronic address: malcolm.ranson@manchester.ac.uk.
FAU - Reck, M
AU  - Reck M
AD  - Department of Thoracic Oncology, Krankenhaus Grosshansdorf, Grosshansdorf, 
      Germany.
FAU - Anthoney, A
AU  - Anthoney A
AD  - Department of Medical Oncology, Leeds Institute of Molecular Medicine and St 
      James' University Hospital, Leeds, UK.
FAU - Hanauske, A-R
AU  - Hanauske AR
AD  - Medical Department, St Georg Hospital, Hamburg, Germany.
FAU - Dean, E
AU  - Dean E
AD  - Department of Medical Oncology, University of Manchester, Christie Hospital, 
      Manchester, UK.
FAU - Melezinek, I
AU  - Melezinek I
AD  - Department of Science, Roche Products Ltd, Welwyn Garden City, UK.
FAU - Klingelschmitt, G
AU  - Klingelschmitt G
AD  - Department of Statistics.
FAU - Kletzl, H
AU  - Kletzl H
AD  - Department of Clinical Pharmacology, F. Hoffmann-La Roche Ltd, Basel, 
      Switzerland.
FAU - Blatter, J
AU  - Blatter J
AD  - Department of Medical Department, Eli Lilly & Co., Indianapolis, IN, USA.
FAU - Twelves, C
AU  - Twelves C
AD  - Department of Medical Oncology, Leeds Institute of Molecular Medicine and St 
      James' University Hospital, Leeds, UK.
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100505
PL  - England
TA  - Ann Oncol
JT  - Annals of oncology : official journal of the European Society for Medical 
      Oncology
JID - 9007735
RN  - 0 (Glutamates)
RN  - 0 (KRAS protein, human)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Quinazolines)
RN  - 04Q9AIZ7NO (Pemetrexed)
RN  - 5Z93L87A1R (Guanine)
RN  - DA87705X9K (Erlotinib Hydrochloride)
RN  - EC 2.7.10.1 (EGFR protein, human)
RN  - EC 2.7.10.1 (ErbB Receptors)
RN  - EC 3.6.5.2 (Proto-Oncogene Proteins p21(ras))
RN  - EC 3.6.5.2 (ras Proteins)
SB  - IM
MH  - Adenocarcinoma/*drug therapy/genetics/secondary
MH  - Adult
MH  - Aged
MH  - Antineoplastic Combined Chemotherapy Protocols/pharmacokinetics/*therapeutic use
MH  - Carcinoma, Large Cell/*drug therapy/genetics/secondary
MH  - Carcinoma, Neuroendocrine/*drug therapy/genetics/secondary
MH  - Carcinoma, Non-Small-Cell Lung/*drug therapy/genetics/secondary
MH  - Carcinoma, Squamous Cell/*drug therapy/genetics/secondary
MH  - Disease Progression
MH  - ErbB Receptors/genetics
MH  - Erlotinib Hydrochloride
MH  - Female
MH  - Glutamates/administration & dosage
MH  - Guanine/administration & dosage/analogs & derivatives
MH  - Humans
MH  - Lung Neoplasms/*drug therapy/genetics/pathology
MH  - Male
MH  - Maximum Tolerated Dose
MH  - Middle Aged
MH  - Mutation/genetics
MH  - Neoplasm Staging
MH  - Pemetrexed
MH  - Proto-Oncogene Proteins/genetics
MH  - Proto-Oncogene Proteins p21(ras)
MH  - Quinazolines/administration & dosage
MH  - Survival Rate
MH  - Time Factors
MH  - Tissue Distribution
MH  - Treatment Outcome
MH  - ras Proteins/genetics
EDAT- 2010/05/07 06:00
MHDA- 2011/02/18 06:00
CRDT- 2010/05/07 06:00
PHST- 2010/05/07 06:00 [entrez]
PHST- 2010/05/07 06:00 [pubmed]
PHST- 2011/02/18 06:00 [medline]
AID - S0923-7534(19)39547-X [pii]
AID - 10.1093/annonc/mdq246 [doi]
PST - ppublish
SO  - Ann Oncol. 2010 Nov;21(11):2233-2239. doi: 10.1093/annonc/mdq246. Epub 2010 May 
      5.