Drugs

Lyseng-Williamson, Katherine

doi: 10.2165/11204490-000000000-00000pmid: 21395360

Levetiracetam (Keppra®, E Keppra®) is an established second-generation anti-epileptic drug (AED). Worldwide, levetiracetam is most commonly approved as adjunctive treatment of partial onset seizures with or without secondary generalization; other approved indications include monotherapy treatment of partial onset seizures with or without secondary generalization, and adjunctive treatment of myoclonic seizures associated with juvenile myoclonic epilepsy and primary generalized tonic-clonic (GTC) seizures associated with idiopathic generalized epilepsy.

Litzow, Mark

doi: 10.2165/11588950-000000000-00000pmid: 21395356

Acute lymphoblastic leukaemia (ALL) in adults is a challenging malignancy in that many patients will show evidence of initial chemotherapy responsiveness but will subsequently relapse. The disease is heterogeneous and outcomes vary dramatically depending on the prognostic factors present in an individual patient. An important determinant of outcome is the age of the patient. The stunning success of therapy in paediatric ALL has led to the use of intensive paediatric regimens in adolescents and young adults with what appear to be improved outcomes. For patients who relapse or have high-risk features, blood and marrow transplantation (BMT) continues to play an important role in the therapeutic armamentarium. The use of reduced-intensity conditioning regimens for allogeneic BMT suggests that outcomes may be improved by this approach. Monoclonal antibodies are showing benefit as single agents in the relapsed setting or in combination with chemotherapy in newly diagnosed patients. In recent years, several new chemotherapeutic agents have shown promise as single agents and are being incorporated into multi-agent chemotherapy. The development of tyrosine kinase inhibitors for Philadelphia chromosome-positive leukaemias has significantly improved outcomes. The molecular revolution has led to the identification of new aberrant molecular pathways in the pathogenesis of ALL, and drugs targeting these aberrancies are in various stages of development preclinically and clinically. These developments bring the hope that therapeutic outcomes in adult ALL can begin to approach those seen in the paediatric setting.

Keisner, Sidney; Shah, Sachin

doi: 10.2165/11588960-000000000-00000pmid: 21395357

Treatment options for renal cell carcinoma (RCC) have multiplied in the past 5 years. Pazopanib is the third tyrosine kinase inhibitor (TKI) and the sixth targeted therapy that has received US FDA approval for the treatment of advanced or metastatic RCC. The primary mechanism of action of pazopanib in RCC is through its antiangiogenic properties via inhibition of the intracellular tyrosine kinase of vascular endothelial growth factor receptor and platelet-derived growth factor receptor. A placebo-controlled phase III study demonstrated that pazopanib significantly improved response rates and progression-free survival (PFS) in both treatment-naïve and cytokine-pretreated patients. Among treatment-naïve patients, the response rate was 32% and PFS was 11.1 months. In cytokine-pretreated patients, the response rate and PFS were 29% and 7.4 months, respectively. Common adverse effects of pazopanib include diarrhoea, hypertension and elevation of liver enzymes. Overall, the adverse effect profile of pazopanib is similar to that of other TKIs used for the treatment of RCC, but variation in the incidence and severity may exist. Pazopanib has an increased propensity to cause hepatotoxicity, which may be fatal in rare cases. Hepatic function must be monitored closely with dose interruption and/or reduction if elevation of hepatic function tests occurs. Pazopanib is administered on an empty stomach at a dose of 800 mg daily until disease progression, but dose reduction may be required in patients with baseline elevation of hepatic function tests, particularly total bilirubin. The minimum dose recommended for baseline hepatic dysfunction or toxicity is 200 mg daily. The potential for drug interactions exists for pazopanib. It is a substrate of cytochrome P450 (CYP) 3A4, P-glycoprotein and breast cancer resistance protein, and it weakly inhibits CYP3A4, CYP2C8 and CYP2D6, and potently inhibits UGT1A1 and OATP1B1. Currently, no study has directly compared pazopanib with other first- or second-line therapies in RCC. However, published clinical trials of pazopanib show similar efficacy outcomes to those of other targeted therapies. Therefore, pazopanib may be considered a first-line treatment option among other therapies including sunitinib, temsirolimus, and bevacizumab plus interferon-α. After failure of cytokine therapy, pazopanib is a treatment option as well as sorafenib or bevacizumab. No study has evaluated pazopanib treatment after failure of another targeted therapy. Future studies will further clarify the comparative efficacy of pazopanib with other agents as well as optimal sequencing with other agents. If similar efficacy is seen among the TKIs, it is likely that varying incidences of adverse effects may be analysed to tailor therapy according to the patient’s individual co-morbidities and preferences.

Chou, Roger

doi: 10.2165/11585410-000000000-00000pmid: 21395354

McKeage, Kate; Romanowski, Barbara

doi: 10.2165/11206820-000000000-00000pmid: 21395359

The AS04-adjuvanted human papillomavirus (HPV) 16/18 vaccine (Cervarix®) is a noninfectious recombinant vaccine produced using purified virus-like particles (VLPs) that induce a strong immunogenic response eliciting high levels of anti-L1 VLP antibodies that persist at levels markedly greater than those observed with natural infection. The vaccine adjuvant (AS04) is composed of monophosphoryl-lipid A, which enhances cellular and humoral immune response, adsorbed to aluminium hydroxide. The vaccine is indicated for the prevention of premalignant cervical lesions and cervical cancer causally related to certain oncogenic HPV types in females aged ≥10 years.

Garnock-Jones, Karly

doi: 10.2165/11206900-000000000-00000pmid: 21395358

Ranibizumab (Lucentis®), a recombinant humanized IgG1 κ isotype monoclonal antibody fragment, is approved in the US for the treatment of macular oedema following retinal vein occlusion (RVO). It binds to the receptor-binding site of active forms of vascular endothelial growth factor-A, inhibiting its biological activity.