Evaluation of the absolute oral bioavailability and bioequivalence of erlotinib, an inhibitor of the epidermal growth factor receptor tyrosine kinase, in a randomized, crossover study in healthy subjects

Journal of Clinical Pharmacology

Volumn 46, Issue 3, 2006, Pages 282-290

  Frohna, Paul ^a   Lu, Jianfeng ^b   Eppler, Steve ^b   Hamilton, Marta ^c   Wolf, Julie ^c   Rakhit, Ashok ^d   Ling, Jie ^b   Kenkare Mitra, Saraswati R ^b   Lum, Bert L ^b  

^a CV THERAPEUTICS INC   (United States)

^b GENENTECH INC   (United States)

^c OSI PHARMACEUTICALS INC   (United States)

^d HOFFMANN LA ROCHE INC   (United States)

Author keywords

Bioavailability; Bioequivalence; Erlotinib

Indexed keywords

CP 396 059; DRUG METABOLITE; EPIDERMAL GROWTH FACTOR RECEPTOR KINASE INHIBITOR; ERLOTINIB; GEFITINIB; OSI 420; QUINAZOLINE DERIVATIVE; UNCLASSIFIED DRUG;

ADULT; AGED; AREA UNDER THE CURVE; ARTICLE; BIOEQUIVALENCE; CLINICAL TRIAL; COMPARTMENT MODEL; CONFIDENCE INTERVAL; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; DIARRHEA; DIZZINESS; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG ERUPTION; DRUG INDUCED HEADACHE; DRUG INFUSION; DRUG TOLERABILITY; FEMALE; HUMAN; HUMAN EXPERIMENT; MALE; NAUSEA; NORMAL HUMAN; RANDOMIZATION; RANDOMIZED CONTROLLED TRIAL; STATISTICAL ANALYSIS;

ADMINISTRATION, ORAL; ADOLESCENT; ADULT; BIOLOGICAL AVAILABILITY; CROSS-OVER STUDIES; DRUG MONITORING; FEMALE; HUMANS; INFUSIONS, INTRAVENOUS; MALE; PROTEIN KINASE INHIBITORS; QUINAZOLINES; RECEPTOR, EPIDERMAL GROWTH FACTOR; SEX FACTORS; THERAPEUTIC EQUIVALENCY;

EID: 32944469063     PISSN: 00912700     EISSN: 15524604     Source Type: Journal    
DOI: 10.1177/0091270005284193     Document Type: Article

References (28)

1. Pollack VA, Savage DM, Baker DA, et al. Inhibition of epidermal growth factor receptor-associated tyrosine phosphorylation in humancarcinomaswith CP-358,744: dynamics of receptor inhibition in situ and antitumor effects in athymic mice. J Pharmacol Exp Ther. 1999 ; 291: 739-748.
2. Higgins BA, Kolinsky KA, Smith M, et al. Antitumor activity of erlotinib (OSI-774, Tarceva) alone or in combination in human nonsmall cell lung cancer tumor xenograft models. Anticancer Drugs. 2004 ; 15: 503-512.
3. Ng SS, Tsao MS, Nicklee T, Hedley DW. Effects of the epidermal growth factor receptor inhibitor OSI-774, Tarceva, on downstream signaling pathways and apoptosis in human pancreatic adenocarcinoma. Mol Cancer Ther. 2002 ; 1: 777-783.
4. Hidalgo M, Siu LL, Nemunaitis J, et al. Phase I and pharmacological study of OSI-774, an epidermal growth factor receptor tyrosine kinase inhibitor, in patientswith advanced solid malignancies. J Clin Oncol. 2001 ; 19: 3267-3279.
5. Pérez-Soler R, Chachoua A, Hammond LA, et al. Determinants of tumor response and survival with erlotinib in patients with nonsmall-cell lung cancer. J Clin Oncol. 2004 ; 22: 3238-3247.
6. Soulieres D, Senzer NN, Vokes EE, Hidalgo M, Agarwala SS, Siu LL. Multicenter phase II study of erlotinib, an oral epidermal growth factor receptor tyrosine kinase inhibitor, in patientswith recurrent or metastatic squamous cell cancer of the head and neck. J Clin Oncol. 2004 ; 22: 77-85.
7. Forero L, Patnaik A, Hammond LA, et al. Phase I, pharmacokinetic (PK) and biologic study of OSI-774, a selective epidermal growth factor receptor (EGFR) tyrosine kinase (TK) inhibitor in combination with paclitaxel and carboplatin. Proc Am Soc Clin Oncol. 2002 ; 21: 1908a - 1908a.
8. Ratain MJ, George CM, Janisch L, et al. Phase I trial of erlotinib (OSI-774) in combination with gemcitabine (G) and cisplatin (P) in patients with advanced solid tumors. Proc Am Soc Clin Oncol. 2002 ; 21: 2115a - 2115a.
9. Forouzesh B, Hidalgo M, Takimoto C, et al. Phase I, pharmacokinetic (PK), and biological studies of the epidermal growth factortyrosine kinase (EGFR-TK) inhibitor OSI-774 in combination with docetaxel. Proc Am Soc Clin Oncol. 2002 ; 21: 81a - 81a.
10. Herbst RS, Johnson DH, Mininberg E, et al. Phase I/II trial evaluating the anti-vascular endothelial growth factor monoclonal antibody bevacizumab in combination with the HER-1/epidermal growth factor receptor tyrosine kinase inhibitor erlotinib for patientswith recurrent non-small-cell lung cancer. J Clin Oncol. 2005 ; 23: 2544-2555.
11. Moore MJ, Goldstein D, Hamm J, et al. Erlotinib improves survival when added to gemcitabine in patients with advanced pancreatic cancer: a phase III trial of the National Cancer Institute of Canada Clinical Trials Group. Proc ASCO Gastrointestinal Cancers Symposium. 2005 ; 121: 77a - 77a.
12. Moyer JD, Barbacci EG, Iwata KK, et al. Induction of apoptosis and cell cycle arrest by CP-358,774, an inhibitor of epidermal growth factor receptor tyrosine kinase. Cancer Res. 1997 ; 57: 4838-4848.
13. Petty JW, Dragnev KH, Memoli VA, et al. Epidermal growth factor receptor tyrosine kinase inhibition represses cyclin D1 in aerodigestive tract cancers. Clin Cancer Res. 2004 ; 10: 7547-7554.
14. Tucker C. Method protocol A2004231-P1: method protocol for the quantification of OSI-774 and major metabolite OSI-420/413 in human EDTA plasma by HPLC/MS/MS. OSI Pharmaceuticals, Inc, Boulder, Colorado.
15. Tarceva [prescribing information]. Melville, NY: Genentech ; 2005.
16. Shepherd FA, Pereira J, Ciuleanu TE, et al. Arandomized placebocontrolled trial of erlotinib in patients with advanced non-small cell lung cancer (NSCLC) following failure of 1st line or 2nd line chemotherapy: a National Cancer Institute of Canada Clinical Trials Group (NCIC CTG) trial. Proc Am Soc Clin Oncol. 2004 ; 23 :LBA booklet 18: 7022a - 7022a.
17. F. Hoffman-LaRoche. Newlung cancer medicineTarceva receives first European approval [press release]. March 22, 2005. Available at: www.roche.com/med-cor-2005-03-22.
18. Davies AM, Lara PN, Lau DH, et al. Intermittent erlotinib in combinationwith docetaxel(DOC): phase I schedules designed to achieve pharmacodynamic separation. Proc Am Soc Clin Oncol. 2005 ; 23: 630s: 7038a - 7038a.
19. Mita CA, Schwartz G, Mita MM, et al. A pilot, pharmacokinetic (PK), and pharmacodynamic (PD) study to determine the feasibility and activity of maximal doses of erlotinib (E) in previously treated patients with advanced non-small-cell lung cancer (NSCLC). Proc Am Soc Clin Oncol. 2005 ; 23: 203s: 3045a - 3045a.
20. Smolarek TA, Vaidya MP, Davis JA, et al. Pharmacokinetics and metabolism of CP-358,774: a potent and selective EGF receptor tyrosine kinase inhibitor. Cancer Res. 1997 ; 38: 4010a - 4010a.
21. Gefitinib [prescribing information]. Wilmington, Del: Astra-Zeneca ; 2005.
22. Mckillop D, McCormick AD, Millar A, et al. Cytrochrome P450-dependent metabolism of gefitinib. Xenobiotica. 2005 ; 35: 39-50.
23. Ranson M, Hammond LA, Ferry D, et al. ZD1839, a selective oral epidermal growth factor receptor-tyrosine kinase inhibitor, is well tolerated and active in patients with solid, malignant tumors: results of a phase I trial. J Clin Oncol. 2002 ; 20: 2240-2250.
24. Herbst RS, Maddox AM, Rothenberg ML, et al. Selective oral epidermal growth factor receptor tyrosine kinase inhibitor ZD1839 is generally well-tolerated and has activity in non-small-cell lung cancer and other solid tumors: results of a phase I trial. J Clin Oncol. 2002 ; 20: 3815-3825.
25. Baselga J, Rischin D, Ranson M, et al. Phase I safety, pharmacokinetic, and pharmacodynamic trial of ZD1839, a selective oral epidermal growth factor receptor tyrosine kinase inhibitor, in patients with five selected solid tumor types. J Clin Oncol. 2002 ; 20: 4292-4302.
26. Thatcher N, Chang A, Parikh P, et al. Results of a phase III placebocontrolled study (ISEL) of gefitinib (IRESSA) plus best supportive care (BSC) in patients with advanced non-small-cell lung cancer (NSCLC) who had received 1 or 2 prior chemotherapy regimens. Proc Am Assoc Cancer Res. 2005 ; 46: LB - 6a.
27. Swaisland H, Laight A, Stafford L, et al. Pharmacokinetics and tolerability of the orally active selective epidermal growth factor receptor tyrosine kinase inhibitor ZD1839 in healthy volunteers. Clin Pharmacokinet. 2001 ; 40: 297-306.
28. Cunningham D, Humblet Y, Siena S, et al. Cetuximab monotherapy and cetuximab plus irinotecan in irinotecanrefractorymetastatic colorectal cancer. N Engl J Med. 2004 ; 351: 337-345.