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Lapatinib

Lapatinib ditosylate is the ditosylate salt of lapatinib, a synthetic, orally-active quinazoline with potential antineoplastic activity. Lapatinib reversibly blocks phosphorylation of the epidermal growth factor receptor (EGFR), ErbB2, and the Erk-1 and-2 and AKT kinases; it also inhibits cyclin D protein levels in human tumor cell lines and xenografts. EGFR and ErbB2 have been implicated in the growth of various tumor types. Check for active clinical trials or closed clinical trials using this agent. (NCI Thesaurus).

Lapatinib ditosylate is the ditosylate salt of lapatinib, a synthetic, orally-active quinazoline with potential antineoplastic activity. Lapatinib reversibly blocks phosphorylation of the epidermal growth factor receptor (EGFR), ErbB2, and the Erk-1 and-2 and AKT kinases; it also inhibits cyclin D protein levels in human tumor cell lines and xenografts. EGFR and ErbB2 have been implicated in the growth of various tumor types.

Lapatinib is a small molecule and a member of the 4-anilinoquinazoline class of kinase inhibitors. It is present as the monohydrate of the ditosylate salt, with chemical name N-(3­ chloro-4-{[(3-fluorophenyl)methyl]oxy}phenyl)-6-[5-({[2­ (methylsulfonyl)ethyl]amino}methyl)-2-furanyl]-4-quinazolinamine bis(4­ methylbenzenesulfonate) monohydrate. It has the molecular formula C₂₉H₂₆ClFN₄O₄S (C₇H₈O₃S)₂ H₂O and a molecular weight of 943.5.

Lapatinib is a yellow solid, and its solubility in water is 0.007 mg/mL and in 0.1N HCl is 0.001 mg/mL at 25° C. Each 250 mg tablet of TYKERB contains 405 mg of lapatinib ditosylate monohydrate, equivalent to 398 mg of lapatinib ditosylate or 250 mg lapatinib free base. The inactive ingredients of TYKERB are: Tablet Core:Magnesium stearate, microcrystalline cellulose, povidone, sodium starch glycolate. Coating: Orange film-coat: FD&C yellow No. 6/sunset yellow FCF aluminum lake, hypromellose, macrogol/PEG 400, polysorbate 80, titanium dioxide.

According to http://en.wikipedia.org/wiki/Lapatinib, On March 13, 2007, the U.S. Food and Drug Administration (FDA) approved lapatinib in combination therapy for breast cancer patients already using capecitabine (Xeloda, Roche).  In February of 2010, Tykerb received accelerated approval as front-line therapy in triple positive breast cancer. Pharmaceutical company GlaxoSmithKline (GSK) markets the drug under the propriety names Tykerb (mostly US) and Tyverb (mostly Europe).  The drug currently has approval for sale and clinical use in the US, Australia, Bahrain,  Israel, Kuwait,  Venezuela, Brazil,  New Zealand, South Korea, Switzerland, Japan, the European Union, and Pakistan.

Lapatinib is used as a treatment for women's breast cancer in treatment naive, ER+/EGFR+/HER2+ breast cancer patients (now often called "triple positive") and in patients who have HER2-positive advanced breast cancer that has progressed after previous treatment with other chemotherapeutic agents, such as anthracycline, taxane-derived drugs, or trastuzumab (Herceptin, Genentech). A 2006 GSK-supported randomized clinical trial on female breast cancer previously being treated with those agents (anthracycline, a taxane and trastuzumab) demonstrated that administrating lapatinib in combination with capecitabine delayed the time of further cancer growth compared to regime that use capecitabine alone. The study also reported that risk of disease progression was reduced by 51%, and that the combination therapy was not associated with increases in toxic side effects. The outcome of this study resulted in a somewhat complex and rather specific initial indication for lapatinib—use only in combination with capecitabine for HER2-positive breast cancer in women whose cancer have progressed following previous chemotherapy with anthracycline, taxanes and trastuzumab. In February of 2010, based on recent studies, GSK issued a press release announcing the approval of lapatinib in first-line therapy in triple positive (hormone receptor, EGFR, HER2) breast cancer patients.

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