This article will review and summarize the current data regarding the influence of the major cytochrome P450 2D6 (CYP2D6) genotypes and CYP2D6 inhibitors on tamoxifen metabolism and clinical efficacy. We will discuss the clinical relevance and limitations of this data and how to best incorporate our current understanding of CYP2D6 genotyping into our clinical practice and discussions with patients.
In the post–Human Genome Project era, “personalized medicine” has become a buzzword. Health-care professionals increasingly have access to gene sequence data, with the promise that this information will improve the health of the individual. In the area of breast oncology, the study of genetic markers associated with clinical outcome has been a relative success story.
The promise of pharmacogenetics is personalization of therapy for individuals through refinement of the risk/benefit profile of pharmaceuticals based on inherited gene mutations. Classic examples of the impact of pharmacogenetics in clinical practice include variants in dihydropyrimidine dehydrogenase and treatment with fluorouracil.
Adult T-cell leukemia/lymphoma (ATL) is defined as a histologically or cytologically proven peripheral T-cell malignancy associated with a retrovirus, human T-cell lymphotropic virus type I (HTLV-1). Southwestern Japan is the district with the highest prevalence of HTLV-1 infection and the highest incidence of ATL in the world. A high prevalence of HTLV-1 infection is also found in the Caribbean islands, tropical Africa, South America, and northern Oceania.
In this issue of ONCOLOGY, Tobinai reviews the management of human T-cell lymphotropic virus type 1 (HTLV-1)–associated adult T-cell leukemia/lymphoma (ATL). Although rare in the United States, an estimated 10 to 20 million people are infected with HTLV-1 worldwide and 2% to 5% will develop ATL.
In this issue of ONCOLOGY, Dr. Tobinai presents a thorough and thoughtful review of the current state of the art of HTLV-related adult T-cell leukemia/lymphoma (ATLL). As described, ATLL is most prevalent in Asia, where it has also been most studied, but is also seen in patients from other HTLV-endemic areas including the Caribbean, South America, and parts of Africa. ATLL is rare in North America and Europe, representing 1% to 2% of T-cell lymphomas compared to 25% in Asia.
This review summarizes the current data on efficacy and rationale of adjuvant treatment for hepatocellular cancer after orthotopic liver transplantation, as well as future prospects. No adjuvant treatment is currently advocated.
In this issue of ONCOLOGY, Kim et al discuss adjuvant therapy after liver transplantation to decrease recurrence of hepatocellular carcinoma (HCC). Liver transplantation offers the best overall and recurrence-free survival for the treatment of stage I and II HCC. The landmark study in 1996 by Mazzaferro demonstrated that liver transplantation of patients with one lesion less than 5 cm or with up to three lesions but all less than 3 cm (the Milan criteria) resulted in low recurrence rates and similar survival to patients without HCC.
This review summarizes the current data on efficacy and rationale of adjuvant treatment for hepatocellular carcinoma (HCC) after orthotopic liver transplantation (OLT). The authors review prognostic factors for disease recurrence and adjuvant therapy after OLT, including systemic chemotherapy, intra-arterial chemoembolization, immunosuppressant effects, and sorafenib (Nexavar). Several interesting questions are raised in the article, including: (1) When is the best time to apply systemic chemotherapy?
A 56-year-old woman was referred to our institution for a left nephroureterectomy after the diagnoses of a nonfunctioning left kidney and noninvasive papillary urothelial carcinoma of the distal left ureter (Ta grade 1). Following the procedure, surveillance cystoscopy and computed tomography (CT) scan of the abdomen and pelvis demonstrated a large bladder tumor with pan-urothelial extension.
The National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology for Non-Hodgkin’s Lymphomas (NHL) have been updated to include ofatumumab (Arzerra) and romidepsin (Istodax). Ofatumumab was added to the NCCN Guidelines as a treatment option for relapsed/refractory disease in patients with chronic lymphocytic leukemia, with and without a 17p deletion. In addition, the updated guidelines include romidepsin as a systemic treatment option for patients with mycosis fungoides and Szary syndrome.
AEterna Zentaris Inc, announced that the US Food and Drug Administration (FDA) has granted Fast Track designation for the PI3K/Akt pathway inhibitor compound, perifosine (KRX-0401), for the treatment of relapsed/refractory multiple myeloma.
Sunesis Pharmaceuticals, Inc, announced that the US Food and Drug Administration has granted voreloxin orphan drug designation for the treatment of acute myeloid leukemia (AML). Sunesis is currently conducting two phase II clinical trials of voreloxin in AML: a single-agent study (REVEAL-1) in newly diagnosed elderly AML patients unlikely to benefit from standard induction chemotherapy and a study evaluating the drug in combination with cytarabine in relapsed/refractory AML.
GenVec, Inc, announced that the US Food and Drug Administration (FDA) has granted orphan drug designation to TNFerade for the treatment of pancreatic cancer.
The American Society of Clinical Oncology (ASCO) released its report, Clinical Cancer Advances 2009: Major Research Advances in Cancer Treatment, Prevention and Screening, an independent assessment of the most significant clinical cancer research studies of the past year, including 15 major advances.
On October 30, the Centers for Medicare & Medicaid Services (CMS) released the final 2010 physician fee schedule that includes a 1% reduction for oncology services for 2010. Oncology will still be subject to a 6% total cut that will be phased in over 4 years. This is less drastic than the 6% cut for 2010 that CMS included in its proposed fee schedule. However, the American Society of Clinical Oncology (ASCO) stated that it is concerned about any cuts to oncology and will be working to mitigate those cuts in the coming months. ASCO sent out a Member Alert November 4, highlighting key components of the fee schedule that affect oncology practices.
Praise From ASTRO
On November 16, 2009, the US Preventive Services Task Force (USPSTF) announced that it is changing its guidelines for mammography and no longer recommends routine screening for women between the ages of 40 and 49. The new guidelines were published in the November 17th issue of Annals of Internal Medicine. In the days that followed, many cancer organizations issued statements on the revised guidelines, a few of which are summarized below.
Advances in Genetics and Treatment Protocols Lead to Significant Progress in Leukemia and Myeloproliferative Disorders
Research presented at the 51st Annual Meeting of the American Society of Hematology (ASH) in New Orleans introduced potential new treatment options and improved diagnostic methods for patients suffering from acute promyelocytic leukemia (APL), chronic myeloid leukemia (CML), infant acute lymphoblastic leukemia (ALL), and myelofibrosis that are based on a better understanding of the underlying genetic causes of these conditions.
Research presented at the 51st Annual ASH Meeting explored optimal induction therapies for managing multiple myeloma and a potential first-line therapy for patients with non-Hodgkin lymphoma (NHL).
Innovative Strategies Improve Outcomes and Reduce Complications Associated With Stem Cell Transplants
The methods and outcomes for stem cell transplants are constantly improving as leading experts continue to investigate new approaches for reducing the serious adverse events associated with the procedure. Research presented at the 51st Annual ASH Meeting took a closer look at complications of stem cell transplants, including veno-occlusive disease and graft-vs-host disease.
The “Mediterranean diet” represents the food consumed in about 16 countries bordering the Mediterranean Sea. Accumulating evidence points to the many health benefits conferred by this diet.