A phase I, open-label, mass balance study of [14C] dacomitinib (PF-00299804) in healthy male volunteers

Cancer Chemotherapy and Pharmacology

Volumn 72, Issue 2, 2013, Pages 379-385

  Bello, Carlo L ^a   Smith, Evan ^a,b   Ruiz Garcia, Ana ^a   Ni, Grace ^a   Alvey, Christine ^a   Loi, Cho Ming ^a  

^a PFIZER INC   (United States)

^b NEUROCRINE BIOSCIENCES INC   (United States)

Author keywords

ADME; Dacomitinib; Healthy volunteers; Mass balance; PF 00299804; Phase I

Indexed keywords

DACOMITINIB; DACOMITINIB C 14; DRUG METABOLITE; RADIOPHARMACEUTICAL AGENT; UNCLASSIFIED DRUG;

ADULT; AGE DISTRIBUTION; AREA UNDER THE CURVE; ARTICLE; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; DIZZINESS; DRUG BLOOD LEVEL; DRUG CLEARANCE; DRUG ELIMINATION; DRUG FECES LEVEL; DRUG HALF LIFE; DRUG METABOLISM; DRUG MONITORING; DRUG SAFETY; DRUG TOLERABILITY; DRUG URINE LEVEL; ELECTROCARDIOGRAPHY; HUMAN; HUMAN EXPERIMENT; INSOMNIA; ISOTOPE LABELING; MALE; MAXIMUM PLASMA CONCENTRATION; NORMAL HUMAN; PHASE 1 CLINICAL TRIAL; PHOTOPHOBIA; PRIORITY JOURNAL; RADIOACTIVITY; SCINTIGRAPHY; TIME TO MAXIMUM PLASMA CONCENTRATION;

ADULT; AREA UNDER CURVE; BIOTRANSFORMATION; CARBON RADIOISOTOPES; CHROMATOGRAPHY, HIGH PRESSURE LIQUID; ELECTROCARDIOGRAPHY; FECES; HALF-LIFE; HUMANS; ISOTOPE LABELING; MALE; MASS SPECTROMETRY; MIDDLE AGED; PROTEIN KINASE INHIBITORS; QUINAZOLINONES; YOUNG ADULT;

EID: 84880922288     PISSN: 03445704     EISSN: 14320843     Source Type: Journal    
DOI: 10.1007/s00280-013-2207-9     Document Type: Article

References (16)

1. Engelman JA, Zejnullahu K, Gale C-M et al (2007) PF00299804, an irreversible pan-ERBB inhibitor, is effective in lung cancer models with EGFR and ERBB2 mutations that are resistant to gefitinib. Cancer Res 67:11924-11932
2. Gonzales AJ, Hook KE, Althaus IW et al (2008) Antitumor activity and pharmacokinetic properties of dacomitinib, a second-generation irreversible pan-erbB receptor tyrosine kinase inhibitor. Mol Cancer Ther 7:1880-1889
3. Pfizer Inc. Data on file
4. Jänne PA, Schellens JH, Engelman JA et al (2008) Preliminary activity and safety results from a phase I clinical trial of dacomitinib, an irreversible pan-HER inhibitor, in patients with NSCLC. J Clin Oncol 26(15S) (abstr. 8027)
5. Jänne PA, Reckamp KL, Koczywas M et al (2009) Efficacy and safety of dacomitinib in patients with advanced NSCLC after failure of at least one prior chemotherapy regimen and prior treatment with erlotinib: a two-arm, phase II trial. J Clin Oncol 27(15S) (abstr. 8063)
6. Jänne PA, Boss DS, Camidge DR et al (2011) Phase I dose-escalation study of the pan-HER inhibitor, PF299804, in patients with advanced malignant solid tumors. Clin Cancer Res 17:1131-1139
7. Boyer MJ, Blackhall FH, Park K et al (2010) Efficacy and safety of PF299804 versus erlotinib: a global, randomized phase II trial in patients with advanced non-small cell lung cancer after failure of chemotherapy. J Clin Oncol 28(18S) (abstr. LBA7523)
8. Mok T, Spigel DR, Park K et al (2010) Efficacy and safety of dacomitinib, an oral, irreversible, pan-human epidermal growth factor receptor tyrosine kinase inhibitor, as first-line treatment of selected patients with advanced non-small cell lung cancer. J Clin Oncol 28(15S) (abstr. 7537)
9. Park K, Heo DS, Cho B et al (2010) Dacomitinib in Asian patients with non-small cell lung cancer refractory to chemotherapy and erlotinib or gefitinib: a phase I/II study. J Clin Oncol 28(15S) (abstr. 7599)
10. Ramalingam SS, Boyer MJ, Park K et al (2010) Randomized phase 2 study of dacomitinib, an irreversible human epidermal growth factor inhibitor, versus erlotinib in patients with advanced non-small cell lung cancer after chemotherapy failure: quantitative and qualitative benefits. Ann Oncol 21(Suppl 8):viii122-viii123
11. Bello CL, LaBadie RR, Ni G et al (2012) The effect of dacomitinib (PF-00299804) on CYP2D6 activity in healthy volunteers who are extensive or intermediate metabolizers. Cancer Chemother Pharmacol 69:991-997
12. Hamilton RA, Garnett WR, Kline BJ (1981) Determination of a mean valproic acid serum level by assay of a single pooled sample. Clin Pharmacol Ther 29:408-413 (Pubitemid 11134120)
13. Scheffler M, Di Gion P, Doroshyenko O et al (2011) Clinical pharmacokinetics of tyrosine kinase inhibitors. Focus on 4-anilinoquinazolines. Clin Pharmacokinet 50:371-403
14. Joshi SS, Ortiz S, Witherspoon JN et al (2010) Effects of epidermal growth factor receptor inhibitor-induced dermatologic toxicities on quality of life. Cancer 116:3916-3923
15. Lynch TJ Jr, Kim ES, Eaby B et al (2007) Epidermal growth factor receptor inhibitor-associated cutaneous toxicities: an evolving paradigm in clinical management. Oncologist 12:610-621 (Pubitemid 350012125)
16. Segaert S, Van Cutsem E (2007) Clinical management of EGFRI dermatologic toxicities: the European perspective. Oncology (Williston Park) 21(11 Suppl. 5):22-26