News

Phase IV:1) Cancer Risks and Postmenopausal Hormone Link ConfirmedPhase III:1) Do Vitamins Protect Against Lung Cancer?2) Longer Life Expectancy in Pancreatic Cancer When Gemcitabine Is Added to Chemotherapy3) Outcomes Improve With Letrozole Treatment in Women With Early-Stage Breast Cancer4. Pemetrexed vs. Docetaxel for Non-Small Cell Lung Cancer TreatmentPhase II:1) Talactoferrin-Alfa Treatment for Non-Small Cell Lung Cancer2) Advanced Carcinoid Systemic Therapy

Phase IV: 1) Cancer Risks and Postmenopausal Hormone Link Confirmed Phase III: 1) Do Vitamins Protect Against Lung Cancer? 2) Longer Life Expectancy in Pancreatic Cancer When Gemcitabine Is Added to Chemotherapy 3) Outcomes Improve With Letrozole Treatment in Women With Early-Stage Breast Cancer 4. Pemetrexed vs. Docetaxel for Non-Small Cell Lung Cancer Treatment Phase II: 1) Talactoferrin-Alfa Treatment for Non-Small Cell Lung Cancer 2) Advanced Carcinoid Systemic Therapy

T umor human papillomavirus (HPV) status is confirmed as a strong and independent prognostic factor for survival of patients with oropharyngeal cancer, report investigators for a large phase III trial established by the Radiation Therapy Oncology Group. Results were presented at the 44th annual meeting of the American Society of Clinical Oncology (ASCO abstract 5510) and published in the New England Journal of Medicine on June 7. Investigators performed a retrospective analysis of the association between tumor HPV status and survival among 323 patients with stage III or IV oropharyngeal squamous cell carcinoma who were enrolled in a randomized trial comparing cisplatin therapy combined with either accelerated- or standard-fractionation radiotherapy. Risk of death among patients with HPV-positive vs HPV-negative cancer was compared using a proportional-hazards model.

German researchers sought to confirm the results of a previous Japanese trial that found patients with extensive-disease small–cell lung cancer (ED SCLC) treated with irinotecan plus cisplatin lived longer than subjects given therapy with etoposide plus cisplatin.

German researchers sought to confirm the results of a previous Japanese trial that found patients with extensive-disease small–cell lung cancer (ED SCLC) treated with irinotecan plus cisplatin lived longer than subjects given therapy with etoposide plus cisplatin.

At the 2010 Gastrointestinal Cancers Symposium, new data from the CRYSTAL trial identified BRAF gene mutations as a poor prognostic indicator in metastatic colorectal cancer (mCRC) but not predictive of response to therapy.

At the 2010 Gastrointestinal Cancers Symposium, new data from the CRYSTAL trial identified BRAF gene mutations as a poor prognostic indicator in metastatic colorectal cancer (mCRC) but not predictive of response to therapy.

Mycosis fungoides (MF), the most common cutaneous T-cell lymphoma, is a low-grade cutaneous lymphoma characterized by skin-homing CD4+ T cells. It is notable for highly symptomatic progressive skin lesions, including patches, plaques, tumors, and erytheroderma, and has a poorer prognosis at later stages. Diagnosis remains difficult owing to MF’s nonspecific skin presentation and identification of the optimal treatment strategy is challenging given the paucity of controlled trials and numerous and emerging treatment options. Management includes topical therapy with the addition of systemic therapy for patients with later-stage disease including tumors; erythroderma; and nodal, visceral, or blood involvement. Topical therapies include mechlorethamine (nitrogen mustard), carmustine (BCNU), steroids, bexarotene gel (Targretin Gel), psoralen plus ultraviolet A (PUVA), ultraviolet B (UVB), and either localized or total skin electron radiotherapy. Systemic therapies include interferon, retinoids, oral bexarotene (Targretin), denileukin diftitox (Ontak), vorinostat (Zolinza), extracorporeal photochemotherapy (photopheresis), and cytotoxic chemotherapy. Herein, we outline clinically relevant aspects of MF, including clinical presentation, pathology, diagnosis, and staging. We describe in detail existing and emerging therapeutics and offer specific recommendations for management of each stage of MF.

The review by Oxnard and Miller provides a thoughtful update on the use of the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) gefitinib (Iressa) and erlotinib (Tarceva) as front-line therapy in patients with non–small-cell lung cancer (NSCLC).

With better disease definition, staging, and monitoring, treatment of extranodal NK/T-cell lymphoma is becoming more rational. A large proportion of patients with localized nasal disease may enjoy prolonged disease-free survival. On the other hand, early HSCT or novel therapy may be recommended for aggressive extranasal disease.

Highlighting the many developments in the area of oculogenetics, Edwin M. Stone, MD, PhD, is concentrating on a gene therapy experiment.

NCCN included a dinner symposium on Maintenance Therapy for Non-Small Cell Lung Cancer.

High-dose melphalan (Alkeran) and autologous stem cell transplantation are commonly incorporated into the initial line of therapy for patients newly diagnosed with multiple myeloma.

Despite recent therapeutic advances, lung cancer continues to be one of the leading causes of cancer-related mortality. Of the various histologic subtypes, non–small-cell lung cancer (NSCLC) is the most common-accounting for approximately 85% of all lung cancers-and will be the focus of this article. In general, the treatment of lung cancer may include surgery, radiation therapy, systemic therapy (eg, chemotherapy with or without targeted therapy), or a combination of the above. Surgery continues to offer the best chance of long-term cure. The initial treatment of stage I and II NSCLC usually entails surgical resection, whereas stage IV disease is primarily treated with systemic agents, in light of the lack of curative potential with surgery and/or radiation therapy alone. It is locally advanced NSCLC, including stage IIIA and IIIB disease, that continues to pose a therapeutic dilemma, given its heterogeneous nature.

Skin cancer is the single most common form of cancer, accounting for more than 75% of all cancer diagnoses. More than 1 million cases of squamous cell and basal cell carcinomas are diagnosed annually, with a lifetime risk of more than one in five. The vast majority of skin cancers can be cured with surgery alone. Resection is the mainstay of therapy, even for skin cancer involving regional lymph nodes or, in some cases, more distant metastatic sites.

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.

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]

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 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.

CHICAGO-FDG-PET imaging of non-small-cell lung cancer patients prior to receiving radiation therapy should not be the basis for determining areas that may benefit from higher doses of radiation, according to research out of Philadelphia’s Thomas Jefferson University Hospital.

An FDA-convened panel of outside experts recommended 12 to 1 against approving approval erlotinib (Tarceva) as an early maintenance therapy for patients with non–small cell lung cancer (NSCLC).

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.

Bendamustine (Treanda) plus rituximab (Rituxan; B/R) was superior to CHOP plus rituximab (CHOP-R) as first-line therapy of indolent lymphoma and mantle cell lymphoma in a multicenter, randomized, controlled trial of the German Study Group on Indolent Lymphoma (StiL). At an oral presentation at the 51st ASH Annual Meeting, experts agreed that this study may be practice-changing.

Since the publication of a meta-analysis in 1995 that demonstrated a modest survival benefit compared to best supportive care, platinum-based chemotherapy became the cornerstone of therapy in the first-line setting in advanced-stage non–small-cell lung cancer (NSCLC) for patients with good performance status.[1] A recent meta-analysis of 16 randomized trials including 2,714 patients demonstrated an advantage of chemotherapy over best supportive care with an absolute improvement in survival of 9% at 12 months.[2]

Researchers are exploring ways to manipulate rituximab (Rituxan) when added to the current standard therapy for diffuse large B-cell lymphoma, specifically shortening the number of treatment days. Preliminary results of a phase III trial showed that rituximab plus CHOP over a 14-day cycle achieved similar response rates and comparable toxicity compared to CHOP on a 21-day cycle in newly diagnosed patients.

With the availability of newer drugs for treating multiple myeloma, such as proteosome inhibitors and immunomodulatory drugs (IMiDs), outcomes and depth of response are steadily improving. These developments have led to a debate about whether high-dose chemotherapy and autologous stem cell transplant should still be considered first-line therapy or whether newer drug regimens should replace transplant.

The treatment of early-stage non–small-cell lung cancer (NSCLC) has undergone a paradigm shift recently with the addition of systemic therapy to local therapy. The use of cisplatin-based chemotherapy following surgery is now a standard approach for patients with stage II–IIIA disease.

The US Food and Drug Administration has approved pemetrexed (Alimta), the first drug available for maintenance therapy of advanced or metastatic lung cancer. Pemetrexed disrupts metabolic processes that are dependent on the B-vitamin folate, a necessary ingredient for cell replication.