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From Wikipedia, the free encyclopedia
Afatinib (INN; trade name Gilotrif in the US and Giotrif in Europe, previously Tomtovok and Tovok) is a drug approved inUnited States, Europe, Taiwan, Mexico, Chile and Japan as well as other countries for the first-line treatment of patients with distinct types of metastatic (EGFR mutation positive) non-small cell lung carcinoma (NSCLC), developed by Boehringer Ingelheim. It acts as an irreversible covalent inhibitor of the receptor tyrosine kinases epidermal growth factor receptor (EGFR) and erbB-2 (HER2).
It has received regulatory approval for use as a treatment for non-small cell lung cancer, although there is emerging evidence to support its use in other cancers such as breast cancer.
Adverse effects by frequency include:
Very common (>10% frequency)
· Diarrhea (>90%)
· Rash/dermatitis acneform
· Stomatitis
· Paronychia
· Decreased appetite
· Nose bleed
· Itchiness
· Dry skin
Common (1–10% frequency)
· Dehydration
· Taste changes
· Dry eye
· Cystitis
· Cheilitis
· Fever
· Runny/stuffy nose
· Low amount of potassium in the blood
· Conjunctivitis
· Increased ALT
· Increased AST
· Hand-foot syndrome
· Muscle spasms
· Kidney impairment and/or failure
Uncommon (0.1-1% frequency)
· Keratitis
· Interstitial lung disease
Like lapatinib and neratinib, afatinib is a protein kinase inhibitor that also irreversibly inhibits human epidermal growth factor receptor 2 (Her2) and epidermal growth factor receptor (EGFR) kinases. Afatinib is not only active against EGFR mutations targeted by first generation tyrosine-kinase inhibitors (TKIs) like erlotinib or gefitinib, but also against mutations such as T790M which are not sensitive to these standard therapies.] Because of its additional activity against Her2, it is being investigated for breast cancer as well as other EGFR and Her2 driven cancers.
In March 2010 a Phase III trial in NSCLC patients called Lux-Lung 5 began with this drug. Fall 2010 interim results suggested the drug extended progression-free survival threefold compared to placebo, but did not extend overall survival. In May 2012, the Phase IIb/III trial Lux-Lung 1 came to the same conclusion.
In January 2015 a Phase III trial in people with NSCLC suggested the drug extended life expectancy in stage IV NSCLC adenocarcinoma with EGFR Mutation type del 19-positive tumors, compared to cisplatin-based chemotherapy by a year (33 months vs. 21 months).] It also shows strong activity against exon 18 mutations (particularly G719) and is currently the preferred EGFR-TKI therapy for exon 18 mutations (particularly G719x).
Phase II results for breast cancer that over-expresses the protein human epidermal growth factor receptor 2 (Her2-positive breast cancer) were described as promising by the authors, with 19 of 41 patients achieving benefit from afatinib. Double-blind Phase III trials are under way to confirm or refute this finding. Her2-negative breast cancers showed limited or no response to the drug. |
