ONCOLOGY Vol 24 No 2

This activity is based on review articles in the journal ONCOLOGY. It is developed from an identified educational need for information about practical management issues in the practice of medical, surgical, and radiation oncology. This activity has been developed and approved under the direction of CME LLC.

The epigenetic control of gene expression has been shown to play an important role in cancer initiation, progression, and resistance. Thus, agents that modify the epigenetic environment of tumors will likely be an important addition to the anticancer arsenal. Specifically, there is much interest in modulating histone acetylation using a new class of drugs, histone deacetylase (HDAC) inhibitors. Preclinical data have demonstrated the efficacy of various HDAC inhibitors as anticancer agents, with the greatest effects shown when HDAC inhibitors are used in combination with other therapies. As a result of encouraging preclinical data, numerous HDAC inhibitors are being investigated in clinical trials either as monotherapies or in conjunction with other treatments such as chemotherapy, biologic therapy, or radiation therapy. In fact, vorinostat and depsipeptide, two actively studied HDAC inhibitors, were recently approved for the treatment of refractory cutaneous T-cell lymphoma. Although the use of HDAC inhibitors has generated great enthusiasm, a significant amount of work still needs to be done in order to understand their mechanisms of action, as well as to determine the appropriate patient characteristics and subsets of cancer for which HDAC inhibitors hold the most potential for effective treatment.

No branch of oncology has been more attuned to the vision of new genetically engineered targeted therapies than the field of hematopoietic malignancies. Ujjani and Cheson have produced a masterful summary of one extremely important component of the targeted therapy revolution-the realm of monoclonal antibodies directed against malignant lymphoma surface antigens.[1] The review presents a wonderful update and a glimpse of future potentially curative macromolecular cocktails. It is an attractive vision.

Large clinical trials have demonstrated that preoperative therapy for primary operable breast cancer improves breast-conservation rates, with equivalent disease-free (DFS) and overall survival (OS) compared to adjuvant therapy.[1] Connolly and Stearns provide an excellent review of additional benefits of neoadjuvant therapy and emphasize the importance of a multidisciplinary approach to treating patients in this setting.

While the administration of neoadjuvant chemotherapy is recommended for women with locally advanced breast cancer, its use in the primary operable setting has been debated and is the focus of this review.

Shabason and colleagues’ review of the development of histone deacetylase (HDAC) inhibitors as treatment for cancers is timely, with an emphasis on therapeutic strategies combining HDAC inhibitors and radiation therapy. As the authors indicate, vorinostat (Zolinza)-originally known as suberoylanilide hydroxamic acid, or SAHA-was the first of the HDAC inhibitors approved by the US Food and Drug Administration (FDA) for clinical use in the treatment of cutaneous T-cell lymphoma (CTCL).[1] In November 2009, a second HDAC inhibitor-romidepsin (Istodax)-received FDA approval for the treatment of CTCL. Currently there is a great deal of competition in the HDAC inhibitor field, as several new and, hopefully, more effective compounds are being developed and entering clinical trials.[2]

Shabason et al have written a thoughtful review of an exciting new class of agents, histone deacetylase (HDAC) inhibitors. While the authors focus primarily on the role of HDAC inhibitors in combination with radiation therapy, we would like to highlight some potential strategies combining these agents with systemic therapies for the treatment of cancer.

he treatment of B-cell malignancies has been revolutionized by the availability of safe and effective monoclonal antibodies. The addition of rituximab to standard chemotherapy regimens prolongs the survival of patients with diffuse large B-cell lymphoma (DLBCL) and follicular non-Hodgkin lymphoma. Nevertheless, indolent and mantle cell lymphomas remain incurable, and 30% to 40% of patients with DLBCL still die from their disease. Much ongoing research has focused on optimizing monoclonal antibody use, integrating them into multiagent regimens, and developing newer antibodies. Attempts to improve on the efficacy of monoclonal antibody–based therapy have included altering the dosing schedule, optimizing patient selection, maintenance therapy, improving upon the rituximab molecule, radioimmunotherapy, as well as combinations with cytotoxic molecules and other novel agents. Preliminary data with a number of treatment regimens are promising in indolent and aggressive lymphomas. The eventual goal of targeted therapies is to individualize treatment to increase response and survival, while reducing treatment-related toxicity.

In my practice as an oncologist specializing in gastrointestinal tract cancers, a recent week was fairly typical. I saw 50 patients, ranging in age from 32 to 87, equally divided between men and women. Though a couple of them have inherited a gene that may have caused their GI cancers, I have no explanation for why most developed their disease. It is as if they were simply struck by lightning.

In the largest survey to date of US oncologists’ attitudes about the cost of cancer treatments, researchers at Tufts Medical Center and the University of Michigan found that 84% of oncologists consider their patients’ out-of-pocket costs when recommending cancer treatment. However, fewer than half of the respondents surveyed frequently discuss cost issues with patients.

Cancer researchers at Children’s Hospital Boston have reported a protein previously unknown to be involved in taxane resistance and could potentially be targeted with drugs, making a cancer more susceptible to chemotherapy. The researchers believe that this protein, prohibitin1, could also serve as a biomarker, allowing doctors to predict a patient’s response to chemotherapy with a simple blood test. The study was published online by the Proceedings of the National Academy of Sciences in its online early edition during the week of January 25.

In this review, Ujjani and Cheson present a useful overview of the array of existing and developing roles for monoclonal antibodies in the management of B-cell non-Hodgkin lymphomas (NHLs). These roles may be characterized as single-agent antibody therapy, use in combination with chemotherapy and/or other antibodies, and use following an initial regimen (consolidation/maintenance). Rituximab (Rituxan), the first monoclonal antibody approved for B-cell NHL, clearly has had greatest application in each of these arenas, but it has now been joined by alemtuzumab (Campath) and ofatumumab (Arzerra) as approved single-agent therapies. Also highlighted are a number of other antibodies aimed at B-cell targets: veltuzumab, GA101, AME-133 (CD20), epratuzumab (CD22), lumiliximab (CD23), galiximab (CD80), dacetuzumab (CD40), mapatumumab, lexatumumab (TRAIL), and approaches to improve antibody therapy such as conjugation with radioisotopes or toxins.

Practitioners of Gerson therapy believe that cancer is caused by an accumulation of toxic substances in the body. They recommend a special diet including high carbohydrate and potassium intake, no sodium or fat, low animal protein, supplementation with exogenous digestive enzymes, and coffee enemas aimed at detoxifying the body and stimulating metabolism. However, available scientific evidence does not support use of Gerson therapy.

The Takeda Oncology Company announced that the US Food and Drug Administration (FDA) has approved a supplemental new drug application (sNDA) for bortezomib (Velcade), which expands the label to include long-term (median follow-up 36.7 months) overall survival (OS) data from the landmark VISTA trial (Velcade as Initial Standard Therapy in Multiple Myeloma: Assessment With Melphalan and Prednisone) and provides specific dosing recommendations for patients with hepatic impairment. The VISTA trial examined the use of bortezomib-based therapy in patients with previously untreated multiple myeloma (MM).

In the lead up to World Cancer Day on February 4, the theme of a campaign launched by the International Union Against Cancer (UICC) was “Cancer can be prevented too.” The campaign was backed by a new scientific report, “Protection Against Cancer-Causing Infections,” which focuses on the nine infections that can lead to cancer.

Agendia, a leader in molecular cancer diagnostics, recently announced that the US Food and Drug Administration (FDA) cleared its MammaPrint breast cancer recurrence test for all ages. MammaPrint is the only FDA-cleared breast cancer recurrence test available to patients and physicians. Over the past 3 years, the FDA has issued four clearances for MammaPrint, covering all aspects of this service.