title: Trametinib: a novel signal transduction inhibitor for the treatment of metastatic cutaneous melanoma.
abstract: OBJECTIVE
  The pharmacology, pharmacokinetics, clinical efficacy, safety, administration, cost, and place in therapy of trametinib for the treatment of metastatic melanoma are reviewed.
  
  
  CONCLUSIONS
  Approximately 40-60% of malignant melanomas have gene mutations at codon 600 of the BRAF gene that result in the activation of the mitogen-activated protein kinase (MAPK) pathway. Trametinib is the first-in-class mitogen-activated, extracellular signal-regulated kinase (MEK) inhibitor that targets a kinase in the MAPK pathway that plays a key role in oncogenic cell proliferation, survival, invasion, tumor angiogenesis, and escape from apoptosis. It is approved by the Food and Drug Administration for use in patients whose tumors express the BRAF V600E or V600K gene mutations. Moreover, trametinib is also indicated for use in combination with dabrafenib (a BRAF inhibitor). Trametinib is not indicated in patients who have received prior BRAF-inhibitor therapy due to poor response and possible cross-resistance. The most common adverse effects associated with the use of trametinib for both monotherapy and combination therapy are rash, diarrhea, peripheral edema, fatigue, and dermatitis. The recommended dosage of trametinib monotherapy is 2 mg orally once daily until disease progression or unacceptable toxicity occurs. With a daily dose of 2 mg, an estimated 30-day course of treatment would cost approximately $9135.
  
  
  CONCLUSIONS
  Trametinib, a novel MEK inhibitor, provides an alternative therapy for patients with BRAF V600 E/K metastatic melanoma as a single agent or in combination therapy for patients not previously treated with a BRAF inhibitor. More studies are needed to determine the safe and effective combination or sequencing of trametinib with other therapies.
authors.affiliation: Clement Chung, Pharm.D., BCOP, BCPS, is Oncology Clinical Pharmacist, Lyndon B. Johnson General Hospital; and Sean Reilly, B.S.Pharm., Pharm.D., is Oncology Clinical Pharmacist, Ben Taub General Hospital, Harris Health System, Houston, TX. clement_t_chung@yahoo.com.
authors.forename: Clement
authors.initials: C
authors.lastname: Chung
authors.affiliation: Clement Chung, Pharm.D., BCOP, BCPS, is Oncology Clinical Pharmacist, Lyndon B. Johnson General Hospital; and Sean Reilly, B.S.Pharm., Pharm.D., is Oncology Clinical Pharmacist, Ben Taub General Hospital, Harris Health System, Houston, TX.
authors.forename: Sean
authors.initials: S
authors.lastname: Reilly
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects* / Q000502:physiology; D008545:Melanoma / Q000175:diagnosis* / Q000188:drug therapy* / Q000453:epidemiology; D011728:Pyridones / Q000494:pharmacology / Q000627:therapeutic use*; D011744:Pyrimidinones / Q000494:pharmacology / Q000627:therapeutic use*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D012878:Skin Neoplasms; D000096142:Cutaneous Malignant Melanoma
chemical_list: D000970:Antineoplastic Agents; D011728:Pyridones; D011744:Pyrimidinones; C560077:trametinib