AIT Drug Reviews

Everolimus in the Treatment of Renal Cell Carcinoma and Neuroendocrine Tumors


Hiu-yan Chan, Ashley B. Grossman, Ronald M. Bukowski

DOI: 10.1007/s12325-010-0045-2

Adv Ther. 2010;27(8). In press.

Abstract | Full text

Renal cell carcinoma (RCC) and neuroendocrine tumors (NET) are uncommon malignancies, highly resistant to chemotherapy, that have emerged as attractive platforms for evaluating novel targeted regimens. Everolimus is an oral rapamycin derivative within the mammalian target of rapamycin class of agents. Preclinical series have shown that everolimus exhibits anticancer effects in RCC and NET cell lines. A phase 3 placebo-controlled study in advanced clear-cell RCC, known as RECORD-1 (for “REnal Cell cancer treatment with Oral RAD001 given Daily”), documented that everolimus stabilizes tumor progression, prolongs progression-free survival and has acceptable tolerability in patients previously treated with the multikinase inhibitors sunitinib and/or sorafenib. Everolimus has been granted regulatory approval for use in sunitinib-pretreated and/or sorafenib-pretreated advanced RCC and incorporated into clinical practice guidelines, and the RECORD-1 safety data are being used to develop recommendations for managing clinically important adverse events in everolimus-treated patients. Ongoing clinical trials are evaluating everolimus as earlier RCC therapy (first-line for advanced disease and as neoadjuvant therapy), in non-clear-cell tumors, and in combination with various other approved or investigational targeted therapies for RCC. Regarding advanced NET, recently published phase 2 data support the ability of everolimus to improve disease control in patients with advanced NET as monotherapy or in combination with somatostatin analogue therapy, octreotide longacting release (LAR). Forthcoming data from phase 3 placebo-controlled trials of everolimus, one focused on monotherapy for pancreatic NET and the other on combination use with octreotide LAR for patients with advanced NET and a history of carcinoid syndrome, will provide insight into its future place in NET therapy. The results of a number of ongoing phase 3 evaluations of everolimus will determine its broader applicability in treating breast cancer (in combination with chemotherapy and hormonal therapy), several advanced gastrointestinal cancers, hepatocellular carcinoma, and lymphoma (in the adjuvant setting), as well as the various lesions associated with the tuberous sclerosis complex tumor suppressor gene.

Advances in Esophageal Stenting: the Evolution of Fully Covered Stents for Malignant and Benign Disease


Drew Schembre

DOI: 10.1007/s12325-010-0042-5

Adv Ther. 2010;27(7). In press.

Abstract | Full text

Self-expanding metal stents have become a leading palliative therapy for dysphagia resulting from esophageal, proximal gastric, and mediastinal cancers. Increasingly, fully covered self-expanding plastic stents and now fully covered metal stents have been used to treat a variety of benign esophageal conditions as well as cancer. Several stent designs are available in the United States and many more internationally. Each design has advantages and limitations. Knowledge of the indications for esophageal stenting and the common side effects associated with different designs allows physicians to choose the best stent for a given condition as well as to anticipate complications such as stent migration or restenosis. Compared with partially covered stents, newer, fully covered metal stents may promote less granulation tissue and subsequent stenosis and may be removable even after several weeks. However, the tradeoff may be more frequent migration. Interest in fully covered metal stents in place of fully covered plastic stents for use in strictures and leaks has also grown, despite the lack of a formal indication for metal stents in benign disease. Unfortunately, rigorous studies of newer stent designs are currently lacking.

Engaging and Empowering Patients to Manage their Type 2 Diabetes, Part I: a Knowledge, Attitude, and Practice Gap?


Manuel Serrano-Gil, Stephan Jacob

Adv Ther. 2010;27(6):321-333.

Abstract | Full text

For over 20 years, the World Health Assembly has recognized diabetes (type 1 and type 2) as a serious threat to national health and economic development and called for action regarding its prevention and control. However, the prevalence of type 2 diabetes continues to rise despite a significant percentage of cases being preventable. Furthermore, data suggest that in many patients diagnosed with type 2 diabetes, glycated hemoglobin (HbA1c) levels remain above the agreed international and national target levels, despite the availability of numerous antihyperglycemic agents, the best intentions of both patient and physician, and the support of the wider healthcare team. Part I of this two-part review considers evidence that seems to suggest there is a knowledge, attitude, and practice (KAP) ap in type 2 diabetes, and that although theoretical knowledge of how type 2 diabetes should be managed exists, the attitude of patients and healthcare professionals may influence the practicalities of implementing life-enhancing changes for patients living day-to-day with the condition. Here, we consider why there may be a KAP gap, how type 2 diabetes is currently being assessed and managed, and whether these current management approaches remain valid in the light of recent studies evaluating the impact of lowering current target HbA1c levels. This article also explores how encouraging patients to self-manage their disease, as well as engaging all stakeholders in the necessary behavioral changes, can positively influence the long-term treatment outcomes of patients with type 2 diabetes.

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