Myra F. Barginear

Profile of panobinostat and its potential for treatment in solid tumors: an update

The histone deacetylase (HDAC) inhibitors have emerged as novel therapies for cancer. Panobinostat (LBH 589, Novartis Pharmaceuticals) is a pan-deacetylase inhibitor that is being evaluated in both intravenous and oral formulations across multiple tumor types. Comparable to the other HDACs, panobinostat leads to hyperacetylation of histones and other intracellular proteins, allowing for the expression of otherwise repressed genes, leading to inhibition of cellular proliferation and induction of apoptosis in malignant cells. Panobinostat, analogous to other HDAC inhibitors, also induces apoptosis by directly activating cellular death receptor pathways. Preclinical data suggests that panobinostat has inhibitory activity at nanomolar concentrations and appears to be the most potent clinically available HDAC inhibitor. Here we review the current status of panobinostat and discuss its role in the treatment of solid tumors.

Need for Inferior Vena Cava Filters in Cancer Patients: A Surrogate Marker for Poor Outcome

Background. Cancer patients have an increased incidence of venous thromboembolism (VTE). Inferior vena cava (IVC) filters are used extensively in the US, and more than 40 000 are inserted annually. The impact on survival of cancer patients receiving IVC filters has not been studied. Methods. A retrospective study examined 206 consecutive cancer patients with VTE to compare the effects of IVC filter placement with anticoagulation (AC) therapy on overall survival (OS), as measured from the time of VTE. Patients were classified into 3 treatment groups: AC (n = 62), IVC filter (77), or combination IVC filter + AC (67). Results. Treatment groups did not differ with respect to age, sex, or albumin levels. Median OS was significantly greater in patients treated with AC (13 months) compared with those treated with IVC filters (2 months) or IVC + AC (3.25 months; P < .0002). IVC patients were 1.9 times more at risk of death than AC only (hazard ratio = .528; 95% confidence interval = .374 to .745). Multivariate analysis revealed that performance status and type of thrombus were not confounders and had no effect on OS. Conclusion. The need for the insertion of an IVC filter projected markedly reduced survival. Patients requiring an IVC filter rather than AC as initial therapy face a 2-fold increase in risk of death. Whether or not this therapeutic procedure has a positive impact on outcome in cancer patients is uncertain. Complications resulting from thrombosis were also analyzed in this cohort. A prospective randomized trial at our institution is addressing this issue.

Perceptions of Older Adults, Hematologists, and Medical Oncologists in Cancer Care.

Objectives The purpose of this study was to assess and compare the perceptions of hematologists, medical oncologists, cancer patients aged 65 years and older, and family members/caregivers regarding the value of a geriatric assessment (GA) in the management of older adults with cancer. Methods Participants included adults with cancer aged 65 years and older (n = 66), patient family members/caregivers (n = 32), and physicians (n = 42). A patient survey, a caregiver/family survey, and an online physician survey targeted to hematologists and medical oncologists were distributed at a large cancer center in a major academic health system in the New York metropolitan area. The &khgr;2 test or the Fisher exact test was used to compare the cohorts for responses to geriatric domains in a GA. Results Comparisons for each of the 17 GA domains between patient and family member and caregiver responses showed concordance, except for the perception of comorbidities; 16.7% of patients indicated that comorbidities were an issue, compared with 29.0% of family/caregivers (P = 0.047). Physicians indicated that a GA would be most helpful in addressing cognitive impairment (91.4%), falls (91.4%), and functional status (88.6%). Conclusions A GA would be useful for physicians and older adults with cancer. Hematologists and medical oncologists recognize the utility of a GA and are receptive to a multidisciplinary geriatrics–oncology collaboration.

Reasons for Chemotherapy Refusal or Acceptance in Older Adults With Cancer

Objectives The majority of Americans diagnosed as having cancer are older than 65 years. They are, however, less likely than younger patients to receive chemotherapy. Our study aimed to better understand the specific reasons for acceptance or refusal of chemotherapy in older adults with cancer. Methods An anonymous cross-sectional survey was distributed during a 6-month study period in a cancer center and an outpatient geriatric medicine faculty practice to patients at least 50 years old with cancer or to their family members. Data collected included reasons for refusal or acceptance, stage/type of cancer, and demographics. The association between chemotherapy refusal or initiation and these factors was assessed using the Fisher exact test. Results Among the 37 respondents meeting the inclusion criteria, 78.4% were patients and 21.6% were family members. The following factors were significantly associated with chemotherapy decision: perceived chemotherapy benefit (P < 0.001), trust in the doctor’s recommendation (P = 0.013), social support (P = 0.018), marital status (P < 0.001), sex (P = 0.037), race/ethnicity (P = 0.021), and whether respondents had a family member or friend who had previously received chemotherapy (P = 0.040). In contrast, none of the clinical variables, such as stage of cancer, previous receipt of chemotherapy, or interest in complementary/alternative medicine showed significant association with a patient’s decision to accept or refuse chemotherapy treatment. Conclusions Chemotherapy decisions made by older adults appear to be associated with demographic and social factors rather than with medical information. Recognizing the influence of these factors for older patients with cancer may help hematologists and oncologists to proactively address specific barriers and explore concerns regarding chemotherapy in older patients whose quality of life and longevity may be affected by treatment.

HMGB1 expression in hormonally independent breast carcinoma

14655 Background: Estrogen and estrogen receptors (ER) play key roles in normal breast development and breast cancer progression; this was observed more than 100 years ago. Hormonal receptor expression correlates with cellular turnover rates, nuclear grade, degree of histological differentiation, and disease-free intervals. The function of ER is modulated by binding of ER to estrogen response elements and mediated by additional cellular proteins. High mobility group box protein1( HMGB1) is a nuclear protein that has been implicated in modulating ER gene interactions, particularly DNA bending. Here we explore HMGB1 expression in breast cancer cell lines. Methods: ER- negative breast cancer cell lines MCF7/adr, MDA-MB-231, BT-20, and ER-positive breast cancer cell lines MCF7/cst, MDA-MB-13, and BT-474 were obtained from the American Type Culture Collection (Rockville, USA). HMGB1 levels were evaluated by quantitative immunoblotting technique. The detection limit of HMGB1 was achieved at concentrations above...