Future oncology
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We retrospectively analyzed data from patients who had been treated with trabectedin at our institution between April 2009 and August 2011. ⋯ Treatment with trabectedin is effective and well tolerated in heavily pretreated soft tissue sarcoma patients. Tapering dexamethasone courses and switching trabectedin administration to an every 4 weeks schedule effectively dealt with persistent fatigue without compromising effectiveness.
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Ibrutinib (formerly PCI-32765) is a potent, covalent inhibitor of Bruton's tyrosine kinase, a kinase downstream of the B-cell receptor that is critical for B-cell survival and proliferation. In preclinical studies, ibrutinib bound to Bruton's tyrosine kinase with high affinity, leading to inhibition of B-cell receptor signaling, decreased B-cell activation and induction of apoptosis. ⋯ Ongoing studies are evaluating ibrutinib in other types of non-Hodgkin's lymphoma, such as diffuse large B-cell lymphoma and Waldenström's macrogobulinemia, in larger Phase III studies in CLL and MCL, and in combination studies with monoclonal antibodies and chemotherapy. Future studies will combine ibrutinib with other promising novel agents currently in development in hematologic malignancies.
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Multicenter Study
Vismodegib for the treatment of basal cell carcinoma: results and implications of the ERIVANCE BCC trial.
The need for effective treatment of patients with locally advanced or metastatic basal cell carcinoma (BCC), in conjunction with major advances in the elucidation of the molecular basis of this tumor has led to the advent of new targeted therapies - namely, hedgehog inhibitors. The rationale for their use in patients with advanced BCC is based on their inhibitory effect on the hedgehog pathway, which is aberrantly activated in BCCs due to mutations of its primary components, PTCH1 and SMO genes. Vismodegib (GDC-0449) is an orally bioavailable hedgehog pathway inhibitor that selectively inhibits SMO. ⋯ This article will outline the rationale, design and available results from the ERIVANCE BCC study and discuss the clinical implications of vismodegib in the management of patients with BCC. Challenges regarding vismodegib use include the recurrence of BCC after drug discontinuation, the development of acquired resistance, the dramatic efficacy in patients with Gorlin syndrome, and class-related drug toxicity. Ongoing clinical trials aim to explore the role of vismodegib in the neoadjuvant setting prior to surgery, the potential use of alternate dosing regimens in order to limit chronic adverse events, as well as the identification of patients with BCC that are more likely to respond to this targeted therapy based on genotypic and/or phenotypic characteristics.
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The 2013 San Antonio Breast Cancer Symposium, held under the auspices of the San Antonio Cancer Therapy & Research Center, the AACR, and Baylor College of Medicine, took place in San Antonio (TX, USA) on 10-14 December 2013. This international Symposium was attended by more than 7000 academic and private physicians and researchers from more than 90 countries, involved in all the fields of breast cancer (BC) research and treatment, including basic, translational and clinical research. Topics of discussion covered all aspects of BC research, from basic science to clinical practice, from prevention to targeted therapies. This report will focus on some of the most important results that were presented during the meeting.
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Eribulin mesylate is a synthetic analog of halichondrin B and is licensed for the treatment of patients with locally advanced or metastatic breast cancer that has progressed following treatment with anthracyclines and taxanes. It was not deemed to be cost effective based on a cost analysis by the National Institute for Health and Care Excellence in England and therefore it is not funded routinely by the National Health Service. The establishment of the Cancer Drugs Fund in England subsequently enabled access. As with any new chemotherapy drug that enters clinical practice for metastatic breast cancer (MBC) it is often used in heavily pretreated patients and the experience in a routine clinical setting can differ from that in a clinical study. We therefore present the experience of the first 25 cases treated at our institution via the Cancer Drugs Fund. ⋯ Eribulin mesylate shows clinical activity; however, there appears to be differences in terms of benefit in patients based on whether patients have been rechallenged with an anthracycline and/or a taxane. These data require confirmation in larger patient groups.