Crizotinib

3 - [( 1R ) -1 - (2,6- dichloro-3- fluorophenyl) ethoxy] -5 - (1- piperidin-4- ylpyrazol -4-yl ) pyridine -2-amine (IUPAC)

L01XE16

Cytostatic

Tyrosine kinase inhibitor

196-199 ° C

Risk

Template: Infobox chemical / molecular formula search available

Crizotinib is a drug to treat a particular form of cancer. It was first presented in 2010 by the pharmaceutical company Pfizer and is located in 2013 still in the study phase, a registration is not yet available in Europe in 2013. In the U.S. it was already approved under the trade name Xalkori for the treatment of advanced stages of a specific subtype of lung cancer.

Crizotinib is an oral aminopyridine, and as such is a tyrosine kinase inhibitor which blocks the ALK tyrosine kinase as well as tyrosine kinases MET and ROS1 (c- ros oncogene 1). Expression of the tyrosine kinase ALK ( anaplastic lymphoma kinase ) was first described in the anaplastic large cell lymphoma, and subsequently also in non- small cell lung cancer and childhood neuroblastoma. In lung cancer (non- small cell lung cancer, NSCLC) shows up at about 5% of all non-small cell lung cancer, a translocation of this gene, which is about 60,000 cases extrapolated annually worldwide.

In a funded by Pfizer multicenter open label phase III study showed in 2013 included in 347 patients with locally spread-out or metastatic ALK -positive NSCLC who had previously received platinum-based chemotherapy, compared to another chemotherapy with pemetrexed or docetaxel a significantly prolonged median progression -free survival of 7.7 months versus 3.0 months ( hazard ratio 0.49) and an effect ( response rate, as complete response or partial response ) at 65 % against 20 %. The subjective patient parameters showed a superiority of crizotinib compared with the standard therapy with greater symptom reduction and improved quality of life.

Common side effects were visual disturbances (60 %), gastrointestinal disorders with diarrhea in 60%, nausea in 55%, vomiting in 47 % and constipation in 42 %, and elevated liver enzyme levels ( 38%). Most side effects, however, were mild to moderate ( grade 1-2 ). The side effects were significantly more frequent and stronger than under the standard therapy in the treatment with Crizotinib was also performed longer.

On October 23, 2012 Crizotinib was approved by the European Medicines Agency (EMA ) under conditions for the treatment of patients with ALK -positive NSCLC. The manufacturing company has been committed to yet nachzuliefern more information and study results. The recommended dosage is 2 × 250 mg daily.

EVALUATION OF THE EFFICACY

In a drug rating of 13 February 2013, the Institute came for Quality and Efficiency in Health Care ( IQWiQ ) concludes that "an additional benefit from crizotinib compared to chemotherapy ( docetaxel / pemetrexed ) for overall survival " and thus " an additional benefit for adult patients with previously treated advanced non- occupied ALK -positive NSCLC " is. This conclusion contradicted an expert committee of the German Society of Hematology and Oncology ( DGHO ). In a statement of 6 March 2013, the appraiser konstatierten indeed a need of improvement study location, but showed many criticisms of IQWiQ as unfounded, Crizotinib designated as " highly effective drug in patients with non - small cell lung cancer and one ALK rearrangement " and attested to the drug a " clinically often dramatic tangible benefit ".