PMID- 20922800
OWN - NLM
STAT- MEDLINE
DCOM- 20110329
LR  - 20151119
IS  - 0008-543X (Print)
IS  - 0008-543X (Linking)
VI  - 117
IP  - 4
DP  - 2011 Feb 15
TI  - Biomarker-based phase I dose-escalation, pharmacokinetic, and pharmacodynamic 
      study of oral apricoxib in combination with erlotinib in advanced nonsmall cell 
      lung cancer.
PG  - 809-18
LID - 10.1002/cncr.25473 [doi]
AB  - BACKGROUND: Apricoxib, a novel once-daily selective cyclooxygenase-2 inhibitor, 
      was investigated in combination with erlotinib for recurrent stage IIIB/IV 
      nonsmall cell lung cancer to determine the maximum tolerated dose, dose-limiting 
      toxicity, and recommended phase II dose (RP2D) based on changes in urinary 
      prostaglandin E(2) metabolite (PGE-M). METHODS: Patients received escalating doses 
      of apricoxib (100, 200, and 400 mg/day) in combination with erlotinib 150 mg/day 
      until disease progression or unacceptable toxicity. Urinary PGE-M was used to 
      assess biologic activity and inform the optimal biologic dose. RESULTS: Twenty 
      patients were treated (3 at 100 mg; 3 at 200 mg; 14 at 400 mg apricoxib) with a 
      median of 4 cycles (range, 2-14 cycles); 8 patients (40%) received prior 
      EGFR-directed therapies. No dose-limiting toxicity was observed. Study 
      drug-related adverse events (AEs) included diarrhea, rash, dry skin, anemia, 
      fatigue, and increased serum creatinine; 4 patients had grade >/= 3 drug-related 
      AEs (diarrhea, perforated duodenal ulcer, hypophosphatemia, and deep vein 
      thrombosis). The RP2D was 400 mg/day based on safety, biologic activity based on 
      decreases in urinary PGE-M, and pharmacokinetics. One patient had a partial 
      response, and 11 had stable disease. Stable disease was observed in patients who 
      had received prior EGFR inhibitor therapy but was greater in patients not 
      previously treated with an EGFR inhibitor. Seventeen patients had elevated 
      urinary PGE-M at baseline, and 14 (70%) had a decrease from baseline, which was 
      associated with disease control. CONCLUSIONS: Apricoxib plus erlotinib was well 
      tolerated and yielded a 60% disease control rate. A phase II trial is currently 
      investigating 400 mg/day apricoxib plus 150 mg/day erlotinib in patients selected 
      based on change in urinary PGE-M.
CI  - Copyright (c) 2010 American Cancer Society.
FAU - Reckamp, Karen
AU  - Reckamp K
AD  - City of Hope Comprehensive Cancer Center, Duarte, California, USA. 
      kreckamp@coh.org
FAU - Gitlitz, Barbara
AU  - Gitlitz B
FAU - Chen, Lin-Chi
AU  - Chen LC
FAU - Patel, Ravi
AU  - Patel R
FAU - Milne, Ginger
AU  - Milne G
FAU - Syto, Mary
AU  - Syto M
FAU - Jezior, Deborah
AU  - Jezior D
FAU - Zaknoen, Sara
AU  - Zaknoen S
LA  - eng
SI  - ClinicalTrials.gov/NCT00596114
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, Non-U.S. Gov't
DEP - 20101004
PL  - United States
TA  - Cancer
JT  - Cancer
JID - 0374236
RN  - 0 (Prostaglandins)
RN  - 0 (Pyrroles)
RN  - 0 (Quinazolines)
RN  - 0 (Sulfonamides)
RN  - 5X5HB3VZ3Z (apricoxib)
RN  - 73303-30-7 (7-hydroxy-5,11-dioxotetranorprostane-1,16-dioic acid)
RN  - DA87705X9K (Erlotinib Hydrochloride)
SB  - IM
MH  - Administration, Oral
MH  - Aged
MH  - Aged, 80 and over
MH  - Antineoplastic Combined Chemotherapy Protocols/adverse 
      effects/pharmacokinetics/*therapeutic use
MH  - Carcinoma, Non-Small-Cell Lung/*drug therapy
MH  - Drug Administration Schedule
MH  - Erlotinib Hydrochloride
MH  - Female
MH  - Humans
MH  - Lung Neoplasms/*drug therapy
MH  - Male
MH  - Middle Aged
MH  - Patient Selection
MH  - Prostaglandins/urine
MH  - Pyrroles/*administration & dosage/adverse effects/pharmacology
MH  - Quinazolines/*administration & dosage/adverse effects/pharmacokinetics
MH  - Sulfonamides/*administration & dosage/adverse effects/pharmacology
EDAT- 2010/10/06 06:00
MHDA- 2011/03/30 06:00
CRDT- 2010/10/06 06:00
PHST- 2010/04/07 00:00 [received]
PHST- 2010/05/11 00:00 [revised]
PHST- 2010/05/11 00:00 [accepted]
PHST- 2010/10/06 06:00 [entrez]
PHST- 2010/10/06 06:00 [pubmed]
PHST- 2011/03/30 06:00 [medline]
AID - 10.1002/cncr.25473 [doi]
PST - ppublish
SO  - Cancer. 2011 Feb 15;117(4):809-18. doi: 10.1002/cncr.25473. Epub 2010 Oct 4.