Oncology: Erlotinib (Tarceva)
Manufacturer: Genentech, OSI Pharmaceuticals Description: Erlotinib, a tyrosine kinase inhibitor, belongs to a group of cancer drugs known as epidermal growth factor receptor (EGFR)-inhibitors. EGFR-inhibitors can destroy some types of cancer cells while causing little harm to normal cells. EGFRs are proteins in the body that help to activate intracellular tyrosine kinase (an enzyme). This activity results in a cascade of intracellular signaling events, leading to cell proliferation, differentiation, cell survival, angiogenesis, and invasion or metastases. These receptors are overexpressed in numerous tumor types, and this overexpression has correlated with more aggressive tumor activity and poor clinical outcomes.
Indication: Erlotinib is intended for patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) after unsuccessful results from at least one prior chemotherapy regimen.
Pharmacology: Structures called EGFRs sit on the surface of many types of cancer cells. The receptors allow epidermal growth factor (EGF) to attach to them. When growth factors (such as transforming growth factor-alpha and EGF) bind to the receptors, tyrosine kinase inside the cell triggers chemical signals to make the cell grow and divide. Erlotinib attaches itself to the tyrosine kinase enzyme and prevents the receptor from being activated. This action appears to stop the cell from dividing. Erlotinib thus seems to stop cancer cells from growing.
Boxed Warning: There have been infrequent reports of serious interstitial lung disease (ILD), including fatalities, in patients receiving erlotinib to treat NSCLC or other advanced solid tumors. In a randomized single-agent study, the incidence of ILD (0.8%) was the same in both the placebo and erlotinib patient groups. The overall incidence in erlotinib-treated patients from all studies (including uncontrolled trials and those using concurrent chemotherapy) was approximately 0.6%.
Reported diagnoses in patients thought to have ILD included pneumonitis, interstitial pneumonia, interstitial lung disease, obliterative bronchiolitis, pulmonary fibrosis, acute respiratory distress syndrome, and lung infiltration. Symptoms started from five days to more than nine months (median, 47 days) after erlotinib therapy was initiated. Most of the cases were associated with confounding or contributing factors such as concomitant or prior chemotherapy, previous radiotherapy, pre-existing parenchymal lung disease, metastatic lung disease, or pulmonary infections. kamagra soft tablets
In the event of the acute onset of new or progressive, unexplained pulmonary symptoms such as dyspnea, cough, and fever, erlotinib therapy should be interrupted pending a diagnostic evaluation. If a diagnosis of ILD is confirmed, erlotinib should be discontinued and appropriate treatment instituted as necessary.
Precautions: Co-treatment with the potent CYP3A4 inhibitor ketoconazole increases the area-under-the-curve (AUC) concentration of erlotinib by two thirds. Caution should be used with coadministration of ketoconazole and other strong CYP3A4 inhibitors (e.g., atanazavir, clarithromycin, nefazodone, saquinavir, telithromycin, troleandomycin, and voriconazole). Pre-treat-ment with the CYP3A4 inducer rifampicin decreases the AUC of erlotinib by approximately two thirds.
Alternative treatments that lack CYP3A4-inducing activity should be considered. If an alternative treatment is unavailable, an erlotinib dose greater than 150 mg should be considered. If the erlotinib dose is adjusted upward, the dose will need to be reduced upon discontinuation of rifampicin or other CYP3A4 inducers. Other CYP3A4 inducers include rifabutin, rifapentin, phenytoin, carbamazepine, phenobarbital, and St. John’s wort.
Asymptomatic increases in liver transaminase levels have been observed in erlotinib-treated patients; therefore, periodic liver function testing of transaminases, bilirubin, and alkaline phosphatase should be considered. Reducing or interrupting the dose of erlotinib may be warranted if changes in liver function are significant. canada drugs pharmacy
Conclusion: NSCLC accounts for about 80% of all lung cancers. It is an aggressive disease, and the overall five-year survival rates are less than 10%. In a randomized, placebo-controlled trial, erlotinib improved symptoms and increased survival in patients with advanced NSCLC. The drug extended the lives of patients and improved quality of life by suppressing symptoms.