Erlonat - Tarceva (Erlotinib)

Erlonat (Erlotinib)  by Natco Pharma (India) is generic version of Tarceva (Erlotinib).

generic tarceva, generic erlotinib

Erlonat (Erlotinib hydrochloride)  (originally coded as OSI-774) is a drug used to treat non-small cell lung cancer, pancreatic cancer and several other types of cancer. It is marketed in the United States by Genetech and OSI Pharmaceuticals and elsewhere by Roche under the tradename Tarceva. 

Similar to Geftinat (gefitinib), Erlonat (Erlotinib) specifically targets theepidermal growth factor receptor (EGFR) tyrosine kinase, which is highly expressed and occasionallymutated in various forms of cancer. It binds in a reversible fashion to the adenosine triphosphate(ATP) binding site of the receptor.[1] For the signal to be transmitted, two members of the EGFR family need to come together to form a homodimer. These then use the molecule of ATP to autophosphorylate each other, which causes a conformational changein their intracellular structure, exposing a further binding site for binding proteins that cause a signal cascade to the nucleus. By inhibiting the ATP, autophosphorylation is not possible and the signal is stopped.

Erlonat (Erlotinib) has shown a survival benefit in the treatment of lung cancer in phase III trials. It has been approved for the treatment of locally advanced or metastatic non-small cell lung cancer that has failed at least one prior chemotherapy regimen. In November 2005, the U.S. Food and Drug Administration (FDA) approved the use of Erlonat (Erlotinib) in combination with gemcitabine for treatment of locally advanced, unresectable, or metastaticpancreatic cancer.[2]

A test for the EGFR mutation in cancer patients has been developed by Genzyme. This may predict who will respond to Erlonat (Erlotinib) and other tyrosine kinase inhibitors. It is reported that responses among patients with lung cancer are seen most often in females who were never smokers, particularly Asian women and those with adenocarcinoma cell type[citation needed].

Erlonat  (Erlotinib) has recently been shown to be a potent inhibitor of JAK2V617F activity. JAK2V617F is a mutant of tyrosine kinase JAK2, is found in most patients with polycythemia vera (PV) and a substantial proportion of patients with idiopathic myelofibrosis or essential thrombocythemia. The study suggests that Erlonat (Erlotinib) may be used for treatment of JAK2V617F-positive PV and other myeloproliferative disorders.

The drug's US patent will expire in 2020. [4]. In India, generic pharmaceutical firm Cipla is battling with Roche against the Indian patent for this drug. In April 2009, the Delhi High Court granted a final approval to Cipla to manufacture and sell its generic version of Erlonat (Erlotinib) in India. [5] Meanwhile, another generic pharmaceutical firm - Natco is also seeking to manufacture the generic version of Erlonat (Erlotinib) in India BUT sell it to patients in Nepal using the TRIPS Agreements' Doha Declaration.

Oral tablets Side effects

Common side effects include:

Rash occurs in the majority of patients. This resembles acne and primarily involves the face and neck. It is self-limited and resolves in the majority of cases, even with continued use. Interestingly, some clinical studies have indicated a correlation between the severity of the skin reactions and increased survival though this has not been quantitatively assessed.[8] TheJournal of Clinical Oncology reported in 2004 that "cutaneous [skin] rash seems to be a surrogate marker of clinical benefit, but this finding should be confirmed in ongoing and future studies."[9] The newsletter Lung Cancer Frontiers reported in its October 2003 issue, "Patients with moderate to severe cutaneous reactions [rashes] have a far better survival, than those with only mild reactions and much better than those with no cutaneous manifestations of drug effects.

• Diarrhea
• Loss of appetite
• Fatigue
• Rarely, interstitial pneumonitis, which is characterized by cough and increased dyspnea. This may be severe and must be considered among those patients whose breathing acutely worsens.
• Rarely, ingrown hairs, such as eyelashes
• It has also been suggested that Erlonat (Erlotinib) can cause hearing loss.
• Partial hair loss (by strands, not typically in clumps)

Rare Side Effects:

In spring, 2009, the US Food and Drug Administration issued a warning on the cancer drug Erlonat (Erlotinib). The FDA reported serious gastrointestinal tract, skin, and ocular disorders in patients taking the drug. In addition, according to a letter released by Genentech and OSI Pharmaceuticals, some people prescribed Erlonat (Erlotinib) have developed serious or fatal gastrointestinal tract perforations; "bullous, blistering, and exfoliative skin conditions, some fatal; and serious eye problems such as corneal lesions. Some of the cases, including ones which resulted in death, were suggestive ofStevens-Johnson syndrome/toxic epidermal necrolysis.

Resistance to treatment

 A key issue with EGFR-directed treatments is that after a period of 8–12 months, the cancer cells become resistant to the treatment, most commonly by recruiting a mutated IGF-1 receptor to act as one of the EGFR partners in the homodimer, so forming a heterodimer.[12] This allows the signal to be transmitted even in the presence of an EGFR inhibitor. Some IGR-1R inhibitors are in various stages of development (based either around tyrphostins such as AG1024 or AG538[13] or pyrrolo[2,3-d]-pyrimidine derivatives such as NVP-AEW541.

Tarceva studies and availability 

In November 2008 a study undertaken by Roche Holding of Switzerland claimed that Tarceva given immediately after chemotherapy may prove to stem the progress of lung cancer. Tarceva blocked the spread of advanced non-small cell lung cancer, researchers found.[15]. However, the report of this study, called SATURN, does not indicate the extent of increase in survival-time.. It is used extensively in Europe and the US.