Erlotinib in African Americans with advanced non-small cell lung cancer: a prospective randomized study with genetic and pharmacokinetic analyses.
Prospective studies on epidermal growth factor receptor (EGFR) inhibitors in African Americans with non-small cell lung cancer (NSCLC) have not previously been performed. In this phase II randomized study, 55 African Americans with NSCLC received 150 mg/day erlotinib or a body weight-adjusted dose with subsequent escalations to the maximum-allowable dose, 200 mg/day, to achieve rash. Erlotinib and OSI-420 exposures were lower than those observed in previous studies, consistent with CYP3A pharmacogenetics implying higher metabolic activity. Tumor genetics showed only two EGFR mutations, EGFR amplification in 17/47 samples, eight KRAS mutations, and five EML4-ALK translocations. Although absence of rash was associated with shorter time to progression (TTP), disease-control rate, TTP, and 1-year survival were not different between the two dose groups, indicating the dose-to-rash strategy failed to increase clinical benefit. Low incidence of toxicity and low erlotinib exposure suggest standardized and maximum-allowable dosing may be suboptimal in African Americans.
1] College of Pharmacy, The Ohio State University, Columbus, Ohio, USA [2] College of Medicine, The Ohio State University, Columbus, Ohio, USA.
M A
MA
Phelps
University of North Carolina College of Medicine, Chapel Hill, North Carolina, USA.
T E
TE
Stinchcombe
College of Medicine, The Ohio State University, Columbus, Ohio, USA.
J S
JS
Blachly
College of Medicine, The Ohio State University, Columbus, Ohio, USA.
W
W
Zhao
1] College of Pharmacy, The Ohio State University, Columbus, Ohio, USA [2] College of Medicine, The Ohio State University, Columbus, Ohio, USA.
L J
LJ
Schaaf
Wexner Medical Center, Department of Medicine and Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio, USA.
S L
SL
Starrett
Center for Biostatistics, The Ohio State University, Columbus, Ohio, USA.
L
L
Wei
College of Medicine, The Ohio State University, Columbus, Ohio, USA.
M
M
Poi
College of Medicine, The Ohio State University, Columbus, Ohio, USA.
D
D
Wang
College of Medicine, The Ohio State University, Columbus, Ohio, USA.
A
A
Papp
College of Pharmacy, The Ohio State University, Columbus, Ohio, USA.
J
J
Aimiuwu
College of Pharmacy, The Ohio State University, Columbus, Ohio, USA.
Y
Y
Gao
College of Public Health, The Ohio State University, Columbus, Ohio, USA.
J
J
Li
College of Medicine, The Ohio State University, Columbus, Ohio, USA.
G A
GA
Otterson
College of Medicine, The Ohio State University, Columbus, Ohio, USA.
W J
WJ
Hicks
University of North Carolina College of Medicine, Chapel Hill, North Carolina, USA.
M A
MA
Socinski
College of Medicine, The Ohio State University, Columbus, Ohio, USA.
M A
MA
Villalona-Calero
D000328:Adult; D001741:Black or African American / Q000235:genetics*; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism; D000069347:Erlotinib Hydrochloride; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010597:Pharmacogenetics; D011446:Prospective Studies; D047428:Protein Kinase Inhibitors / Q000493:pharmacokinetics / Q000627:therapeutic use; D011799:Quinazolines / Q000493:pharmacokinetics / Q000627:therapeutic use*
D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D000069347:Erlotinib Hydrochloride