Erlotinib

Structural formula
General
Non-proprietary name	Erlotinib
other names	N - (3-ethynylphenyl) -6,7-bis (2-methoxyethoxy) quinazolin-4-amine; OSI 774;
Molecular formula	C 22 H 23 N 3 O 4 (Erlotinib) ; C 22 H 23 N 3 O 4 HCl (Erlotinib hydrochloride) ;
External identifiers / databases
EC number	689-196-2
ECHA InfoCard	100.216.020
PubChem	176870
ChemSpider	154044
DrugBank	DB00530
Wikidata	Q418369
Drug information
ATC code	L01 XE03
Drug class	Tyrosine kinase inhibitor
properties
Molar mass	393.44 g · mol -1 (erlotinib)
safety instructions
	Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed
GHS labeling of hazardous substances Caution
H and P phrases	H: 351-413
	P: ?
	As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Erlotinib is a selective inhibitor of the tyrosine kinase domain of the EGF receptor . It was approved in the EU in 2005 under the name Tarceva for the treatment of lung cancer (non-small cell lung carcinoma), and at the beginning of 2007 the indication was expanded for the treatment of pancreatic cancer ( pancreatic cancer ).

pharmacology

Erlotinib is a tyrosine kinase inhibitor that can block tumor cell growth. By blocking tyrosine kinase activity within the cell, Erlotinib prevents signal transmission via the growth factor receptor HER1 (human epidermal growth factor receptor 1), also known as EGFR ( epidermal growth factor receptor ), which is important for cell growth .

Approved areas of application

In non-small cell lung cancer ( Non Small Cell Lung Cancer , NSCLC) Erlotinib is used in advanced stages of the disease, in which a conventional chemotherapy has failed and there is a L858R mutation in the epidermal growth factor receptor (EGFR).

Life-prolonging effects in non-small cell lung cancer were only demonstrated in the TRIBUTE study carried out at the MD Anderson Cancer Center in Houston, however, for lifelong non-smokers.

Approval of Erlotinib (2015)
time	Admission requirement
Non-small cell lung cancer (NSCLC)
First line	in NSCLC with EGFR mutation
Alternation maintenance therapy	in locally advanced or metastatic NSCLC with activating EGFR mutations and unchanged disease status after first-line therapy
Second line	in NSCLC with or without EGFR mutation
Metastatic pancreatic cancer
First line	in combination with gemcitabine

Studies are currently being carried out on the use of Erlotinib as a primary medication and in combination therapy for lung cancer.

Erlotinib has been approved in the EU since September 2005 for the treatment of advanced or metastatic lung cancer (NSCLC) who have received at least one prior chemotherapy. The approval was granted regardless of the EGFR mutation status. In the following years, the approval was expanded so that Erlotinib is now also approved as a first-line therapy for the above-mentioned patient group if an EGFR mutation is present.

The recommended dose for lung cancer is 150 mg once a day.

In January 2007, Tarceva was approved in combination with the chemotherapeutic agent gemcitabine in the first-line treatment of patients with metastatic pancreatic cancer ( pancreatic cancer ). For the non-metastatic, locally advanced pancreatic carcinoma, no survival advantage could be proven and there is no approval for this.

The recommended dose for pancreatic cancer is 100 mg once a day.

Side effects

The most common side effects of erlotinib are an acne- like rash and diarrhea , while the haematological toxicity is low, especially when compared to alternative drugs such as pemetrexed or docetaxel . The so-called rash occurs in about two-thirds of the patients treated with erlotinib to different degrees. The results of clinical studies show that there is a link between the severity of the rash and the response to the drug: the stronger the rash, the higher the response to erlotinib.

In May 2009, Hoffmann-La Roche AG informed health professionals through the Federal Institute for Drugs and Medical Devices about the increased risk of gastrointestinal perforation during treatment with Erlotinib. Accordingly, the simultaneous use of painkillers of the type of non-steroidal anti-inflammatory drugs is contraindicated .

Trade name

Tarceva (EU, CH, USA), ( Roche )

Web links

Erlotinib / Tarceva page. European approval authority

Individual evidence

↑ Template: CL Inventory / not harmonized There is not yet a harmonized classification for this substance . A labeling of 4 - [(3-ethynylphenyl) amino] -6,7-bis (2-methoxyethoxy) quinazoline in the Classification and Labeling Inventory of the European Chemicals Agency (ECHA), accessed on February 10, is reproduced from a self-classification by the distributor 2020.
↑ Summary of the EPAR for the public. (PDF; 130 kB) European Medicines Agency, EMA (German).
↑ A $ 67 Million Fine for False Claims on Erlotinib . In: The American Journal of Managed Care (English)
↑ Erlotinib (Tarceva®) Plus Chemotherapy Fails to Improve Overall Survival in Non-Small Cell Lung Cancer ( Memento from March 2, 2009 in the Internet Archive )
↑ ^a ^b ^c APPENDIX I: SUMMARY OF CHARACTERISTICS OF THE MEDICINAL PRODUCT. (PDF) European Medicines Agency, accessed January 3, 2016 .
↑ Wide range of uses for Erlotinib in NSCLC. Oncotrends, June 4, 2014, accessed January 3, 2016 .
↑ Summary of the European Public Assessment Report (EPAR). European Medicines Agency, EMA (English).
↑ Rote-Hand-Brief information on the occurrence of gastrointestinal perforations in connection with the use of Erlotinib (Tarceva) (PDF; 656 kB) from May 25, 2009; Retrieved May 31, 2012.

[1] Template: CL Inventory / not harmonized There is not yet a harmonized classification for this substance . A labeling of 4 - [(3-ethynylphenyl) amino] -6,7-bis (2-methoxyethoxy) quinazoline in the Classification and Labeling Inventory of the European Chemicals Agency (ECHA), accessed on February 10, is reproduced from a self-classification by the distributor 2020.

[2] Summary of the EPAR for the public. (PDF; 130 kB) European Medicines Agency, EMA (German).

[3] A $ 67 Million Fine for False Claims on Erlotinib . In: The American Journal of Managed Care (English)

[4] Erlotinib (Tarceva®) Plus Chemotherapy Fails to Improve Overall Survival in Non-Small Cell Lung Cancer ( Memento from March 2, 2009 in the Internet Archive )

[EMA-5] APPENDIX I: SUMMARY OF CHARACTERISTICS OF THE MEDICINAL PRODUCT. (PDF) European Medicines Agency, accessed January 3, 2016 .

[6] Wide range of uses for Erlotinib in NSCLC. Oncotrends, June 4, 2014, accessed January 3, 2016 .

[7] Summary of the European Public Assessment Report (EPAR). European Medicines Agency, EMA (English).

[8] Rote-Hand-Brief information on the occurrence of gastrointestinal perforations in connection with the use of Erlotinib (Tarceva) (PDF; 656 kB) from May 25, 2009; Retrieved May 31, 2012.