Gefitinib

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Structural formula
Structural formula of Gefitinib
General
Non-proprietary name Gefitinib
other names

N - (3-chloro-4-fluorophenyl) -7-methoxy-6- [3- (morpholin-4-yl) propoxy] quinazolin-4-amine ( IUPAC )

Molecular formula C 22 H 24 ClFN 4 O 3
Brief description

white, crystalline, non- hygroscopic powder

External identifiers / databases
CAS number 184475-35-2
EC number 643-034-7
ECHA InfoCard 100.171.043
PubChem 123631
ChemSpider 110217
DrugBank DB00317
Wikidata Q417824
Drug information
ATC code

L01 XE02

Drug class

Cytostatics

Mechanism of action

Tyrosine kinase inhibitor

properties
Molar mass 446.90 g · mol -1
Physical state

firmly

Melting point

119–120 ° C (crystals from toluene )

solubility

Easily soluble in glacial acetic acid and in dimethyl sulfoxide , soluble in pyridine , sparingly soluble in tetrahydrofuran and slightly soluble in methanol , ethanol , ethyl acetate , 2-propanol and acetonitrile

safety instructions
Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed
GHS labeling of hazardous substances
07 - Warning 09 - Dangerous for the environment

Caution

H and P phrases H: 302-400
P: 264-273-301 + 312-330
As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Gefitinib ( trade name Iressa , AstraZeneca ) is a drug from the class of tyrosine kinase inhibitors to be taken as a tablet . The usual dosage is 250 mg daily.

Mechanism of action

Gefitinib mainly inhibits the tyrosine kinases from the EGFR family ( Epidermal Growth Factor Receptor ). EGF receptors are overexpressed in some tumors . Inhibition of the EGF receptors leads to a slowdown in tumor growth or even to tumor regression.

Study situation on application

In 2009 and 2010, therapeutic studies for the treatment of patients with non-small cell lung cancer were published in which the administration of Gefitinib was compared with conventional chemotherapy. In a subset of these patients, treatment with gefitinib was shown to be more effective than treatment with “standard” chemotherapy consisting of carboplatin / cisplatin and taxol . However, gefitinib was only more effective if the corresponding patients had mutations in the EGFR gene. In the absence of such mutations, gefitinib was less effective than standard therapy. These mutations were more common in female patients, patients who had never smoked, and patients with adenocarcinoma.

These results led the American Society of Clinical Oncology to recommend the use of gefitinib in patients with EGFR mutations in its 2009 guidelines for the treatment of non-small cell lung cancer.

On 24 June 2009, the issued European Commission said AstraZeneca AB, a marketing authorization of Iressa throughout the European Union for the treatment of non-small cell lung cancer with activating EGFR mutations.

Unwanted side effects

The main possible side effects of Gefitinib are rashes and diarrhea .

Individual evidence

  1. ^ A b c The Merck Index : An Encyclopedia of Chemicals, Drugs, and Biologicals. 14th edition. Merck & Co., Whitehouse Station, NJ, USA, 2006, ISBN 0-911910-00-X .
  2. ↑ a b Safety data sheet from Caymanchem , accessed on May 26, 2020.
  3. ↑ TS Mok, YL Wu, S. Thongprasert, CH Yang, DT Chu, N. Saijo, P. Sunpaweravong, B. Han, B. Margono, Y. Ichinose, Y. Nishiwaki, Y. Ohe, JJ Yang, B. Chewaskulyong, H. Jiang, EL Duffield, CL Watkins, AA Armor, M. Fukuoka: Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. In: N Engl J Med . 361 (10), 2009, pp. 947-957. PMID 19692680 .
  4. ↑ T. Mitsudomi, S. Morita, Y. Yatabe, S. Negoro, I. Okamoto, J. Tsurutani, T. Seto, M. Satouchi, H. Tada, T. Hirashima, K. Asami, N. Katakami, M Takada, H. Yoshioka, K. Shibata, S. Kudoh, E. Shimizu, H. Saito, S. Toyooka, K. Nakagawa, M. Fukuoka; West Japan Oncology Group: Gefitinib versus cisplatin plus docetaxel in patients with non-small-cell lung cancer harboring mutations of the epidermal growth factor receptor (WJTOG3405): an open label, randomized phase 3 trial. In: Lancet Oncol. 11 (2), 2010, pp. 121-128. PMID 20022809 .
  5. ↑ CG Azzoli, S. Baker Jr, S. Temin, W. Pao, T. Aliff, J. Brahmer, DH Johnson, JL Laskin, G. Masters, D. Milton, L. Nordquist, DG Pfister, S. Piantadosi, JH Schiller, R. Smith, TJ Smith, JR Strawn, D. Trent, G. Giaccone; American Society of Clinical Oncology: American Society of Clinical Oncology Clinical Practice Guideline update on chemotherapy for stage IV non-small-cell lung cancer. In: J Clin Oncol . 27 (36), 2009, pp. 6251-6266. PMID 19917871 .
  6. ↑ EMEA: EPAR summary for the public: Iressa - Gefitinib (PDF; 39 kB).