Contents

Search

erlotinib (Tarceva)

Tradename: Tarceva Indications: 1) advanced non-small-cell lung carcinoma a) useful in patients with activating EGFR gene mutation - extends life 2 months longer than placebo when used for maintenance after platinum-based chemotherapy [1,2,9] - extends progression-free survival 4 months vs placebo when used 1st line to treat advanced EGFR gene mutation positive NSCLC [10] b) alternative to docetaxel c) second-line treatment option [6] {NGC, NICE} 2) pancreatic cancer, adjunct to gemcitabine 3) orphan drug for malignant gliomas [8] Contraindications: - not recommended for use in combination with platinum-based chemotherapy Dosage: 100-150 mg PO QD Tabs: 25 mg, 100 mg, 150 mg Pharmacokinetics: - metabolized by cyt P450 3A4 Adverse effects: 1) diarrhea 2) rash in 75% - acneiform rash, resembling acne or folliculitis - most prominent on the head, neck, & upper chest or back - treat with topical 1% clindamycin - oral doxycycline is alternative 3) increased liver function tests 4) interstitial lung disease (small risk) - cough, fever, dyspnea 5) cases of hepatic failure & hepatorenal syndrome, including fatalities [4] 6) gastrointestinal perforation (including fatalities) [5] 7) bullous, blistering and exfoliative skin conditions: [5] a) Stevens-Johnson syndrome b) toxic epidermal necrolysis c) in some cases fatal 8) corneal perforation, corneal ulceration [5] Drug interactions: - drugs that induce or inhibit cyt P450 3A4 Laboratory: - EGFR gene mutation Mechanism of action: - inhibits tyrosine kinase activity of EGF receptor - binds to ATP-binding site in kinase domain of EGFR - prolong - inhibits JAK2 (V617F), a mutant form of the tyrosine kinase JAK2, found in patients with polycythemia vera, idiopathic myelofibrosis, or essential thrombocythemia [7] Notes: Cost = $2000/month

Interactions

drug adverse effects (more general classes)

General

EGF receptor (EGFR) inhibitor small inhibitory antineoplastic agent (ib drug)

Properties

INHIBITS: protein kinase

Database Correlations

PUBCHEM correlations

References

  1. Prescriber's Letter 12(1):5 2005 FDA Approves New Drug for the Most Common Type of Lung Cancer Detail-Document#: 210104 (subscription needed) http://www.prescribersletter.com
  2. Journal Watch 25(17):136, 2005 Shepherd FA, Rodrigues Pereira J, Ciuleanu T, Tan EH, Hirsh V, Thongprasert S, Campos D, Maoleekoonpiroj S, Smylie M, Martins R, van Kooten M, Dediu M, Findlay B, Tu D, Johnston D, Bezjak A, Clark G, Santabarbara P, Seymour L; National Cancer Institute of Canada Clinical Trials Group. Erlotinib in previously treated non-small-cell lung cancer. N Engl J Med. 2005 Jul 14;353(2):123-32. PMID: 16014882 - Tsao MS, Sakurada A, Cutz JC, Zhu CQ, Kamel-Reid S, Squire J, Lorimer I, Zhang T, Liu N, Daneshmand M, Marrano P, da Cunha Santos G, Lagarde A, Richardson F, Seymour L, Whitehead M, Ding K, Pater J, Shepherd FA. Erlotinib in lung cancer - molecular and clinical predictors of outcome. N Engl J Med. 2005 Jul 14;353(2):133-44. PMID: 16014883 - Doroshow JH. Targeting EGFR in non-small-cell lung cancer. N Engl J Med. 2005 Jul 14;353(2):200-2. No abstract available. PMID: 16014890
  3. Moore MJ, Goldstein D, Hamm J, Figer A, Hecht JR, Gallinger S, Au HJ, Murawa P, Walde D, Wolff RA, Campos D, Lim R, Ding K, Clark G, Voskoglou-Nomikos T, Ptasynski M, Erlotinib Plus Gemcitabine Compared With Gemcitabine Alone in Patients With Advanced Pancreatic Cancer: A Phase III Trial of the National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol. 2007 Apr 23; [Epub ahead of print] PMID: 17452677
  4. FDA MedWatch http://www.fda.gov/medwatch/safety/2008/safety08.htm#Tarceva
  5. FDA MedWatch http://www.fda.gov/medwatch/safety/2009/safety09.htm#Tarceva
  6. Lim MY Non-Small Cell Lung Cancer: 5 Management Challenges. Medscape. Nov 30, 2016 http://reference.medscape.com/features/slideshow/non-small-cell-lung-cancer
  7. PubChem: 176870
  8. Medscape: erlotinib (Tarceva) Antineoplastics, Tyrosine Kinase Inhibitor; Antineoplastics, EGFR Inhibitor
  9. Neal JW. The SATURN trial: the value of maintenance erlotinib in patients with non-small-cell lung cancer. Future Oncol. 2010 Dec;6(12):1827-32. PMID: 21142856 Free PMC Article - Coudert B, Ciuleanu T, Park K et al SATURN Investigators. Survival benefit with erlotinib maintenance therapy in patients with advanced non-small-cell lung cancer (NSCLC) according to response to first-line chemotherapy. Ann Oncol. 2012 Feb;23(2):388-94. Epub 2011 May 24. PMID: 21610154
  10. Rosell R, Carcereny E, Gervais R et al Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial. Lancet Oncol. 2012 Mar;13(3):239-46 PMID: 22285168