Afatinib[2] (INN; trade name Gilotrif in the US and Giotrif in Europe, previously Tomtovok and Tovok[3]) is a drug approved in United 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.[4][5][6] It acts as an irreversible covalent inhibitor of the receptor tyrosine kinases epidermal growth factor receptor (EGFR) and erbB-2 (HER2).
Contents [hide]
1 Medical uses
2 Adverse effects
3 Mechanism of action
4 References
Medical uses[edit]
It has received regulatory approval for use as a treatment for non-small cell lung cancer,[7][8][9][10] although there is emerging evidence to support its use in other cancers such as breast cancer.[11]
In October 2010 a Phase III trial in NSCLC patients called Lux-Lung 5 began with this drug.[12] Fall 2010 interim results suggested the drug extended progression-free survival threefold compared to placebo, but did not extend overall survival.[13] In May 2012, the Phase IIb/III trial Lux-Lung 1 came to the same conclusion.[14]
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.[11] 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.[15]
Adverse effects[edit]
Adverse effects by frequency:[7][8][9][1][10]
Very common (>10% frequency):
Diarrhoea (>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
Mechanism of action[edit]
Like lapatinib and neratinib, afatinib is a tyrosine kinase inhibitor (TKI) 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 TKIs like erlotinib or gefitinib, but also against those not sensitive to these standard therapies.[citation needed] Because of its additional activity against Her2, it is being investigated for breast cancer as well as other EGFR and Her2 driven cancers.[5]
Contents [hide]
1 Medical uses
2 Adverse effects
3 Mechanism of action
4 References
Medical uses[edit]
It has received regulatory approval for use as a treatment for non-small cell lung cancer,[7][8][9][10] although there is emerging evidence to support its use in other cancers such as breast cancer.[11]
In October 2010 a Phase III trial in NSCLC patients called Lux-Lung 5 began with this drug.[12] Fall 2010 interim results suggested the drug extended progression-free survival threefold compared to placebo, but did not extend overall survival.[13] In May 2012, the Phase IIb/III trial Lux-Lung 1 came to the same conclusion.[14]
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.[11] 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.[15]
Adverse effects[edit]
Adverse effects by frequency:[7][8][9][1][10]
Very common (>10% frequency):
Diarrhoea (>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
Mechanism of action[edit]
Like lapatinib and neratinib, afatinib is a tyrosine kinase inhibitor (TKI) 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 TKIs like erlotinib or gefitinib, but also against those not sensitive to these standard therapies.[citation needed] Because of its additional activity against Her2, it is being investigated for breast cancer as well as other EGFR and Her2 driven cancers.[5]
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