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.

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 χ(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.

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.

Trastuzumab-DM1: a clinical update of the novel antibody-drug conjugate for HER2-overexpressing breast cancer.

Trastuzumab is a monoclonal antibody targeted against the HER2 tyrosine kinase receptor. Although trastuzumab is a very active agent in HER2-overexpressing breast cancer, the majority of patients with metastatic HER2-overexpressing breast cancer who initially respond to trastuzumab develop resistance within 1 year of initiation of treatment and, in the adjuvant setting, progress despite trastuzumab-based therapy. The antibody-drug conjugate trastuzumab-DM1 (T-DM1) was designed to combine the biological activity of trastuzumab with the targeted delivery of a highly potent antimicrotubule agent, DM1 (N-methyl-N-[3-mercapto-1-oxopropyl]-l-alanine ester of maytansinol), a maytansine derivative, to HER2-overexpressing breast cancer cells. T-DM1 is the first antibody-drug conjugate with a nonreducible thioether linker in clinical trials. Phase I and II clinical trials of T-DM1 as a single agent and in combination with paclitaxel, docetaxel and pertuzumab have shown clinical activity and a favorable safety profile in patients with HER2-positive metastatic breast cancer. Two randomized phase III trials of T-DM1 are awaiting final results; the EMILIA trial is evaluating T-DM1 compared with lapatinib plus capecitabine, and early positive results have been reported. The MARIANNE trial is evaluating T-DM1 plus placebo versus T-DM1 plus pertuzumab versus trastuzumab plus a taxane. Here, we summarize evidence from clinical studies and discuss the potential clinical implications of T-DM1.

Investigating the benefit of adding a vena cava filter to anticoagulation with fondaparinux sodium in patients with cancer and venous thromboembolism in a prospective randomized clinical trial.

BACKGROUND: The benefit of adding a vena cava filter to anticoagulation in treating cancer patients with venous thromboembolism remains controversial. We initiated this study as the first prospectively randomized trial to evaluate the addition of a vena cava filter placement to anticoagulation with the factor Xa inhibitor fondaparinux sodium in patients with cancer. METHODS: Sixty-four patients with deep vein thrombosis (86 %) and/or pulmonary embolism (55 %) were randomly assigned to receive anticoagulation with fondaparinux sodium with or without a vena cava filter. Endpoints included rates of complications by treatment arm, recurrent thromboembolism, complete resolution of thromboembolism, and survival rates. RESULTS: No patient had a recurrent deep vein thrombosis; two (3 %) patients had new pulmonary emboli, one in each randomized cohort. Major bleeding occurred in three patients (5 %). Two patients on the vena cava filter arm (7 %) had complications from the filter. Median survivals were 493 days in the anticoagulation only arm and 266 days for anticoagulation + vena cava filter (p < 0.57). Complete resolution of venous thromboembolism occurred in 51 % of patients within 8 weeks of initiating anticoagulation. CONCLUSIONS: No advantage was found for placement of a vena cava filter in addition to anticoagulation with fondaparinux sodium in terms of safety, recurrent thrombosis, recurrent pulmonary embolism, or survival in this prospective randomized trial evaluating anticoagulation plus a vena cava filter in cancer patients. Favorable complete resolution rates of thrombosis were observed on both study arms.

Primary intracranial leiomyosarcoma in an HIV-infected patient.

Primary intracranial leiomyosarcomas are rare tumors arising from the mesenchymal cells of the dura matter or the cerebral blood vessels. Only 14 cases of primary intracranial leiomyosarcoma are reported in the literature. We report a case of primary intracranial leiomyosarcoma in an human immunodeficiency virus-positive patient with a CD4 count of 14 cells/µL. Additionally, in-situ hybridization of Epstein-Barr virus (EBV) early RNA stained sections highlighted the tumor cells, consistent with the presence of EBV. Review of the literature strongly suggests an association between AIDS, EBV, and primary intracranial leiomyosarcoma. Given the paucity of information in the literature, we review possible chemotherapeutic agents for treatment of primary intracranial leiomyosarcoma in patients refractory to surgical resection and radiation therapy.

Tamoxifen metabolite isomer separation and quantification by liquid chromatography-tandem mass spectrometry.

Tamoxifen (Tam), the antiestrogen used to treat estrogen receptor-positive breast cancer is a pro-drug that is converted to its major active metabolites, endoxifen and 4-hydroxy-tamoxifen (4-OH-Tam) by various biotransformation enzymes of which cytochrome P450-2D6 (CYP2D6) is key. The usual Tam dose is 20 mg daily; however, the plasma active metabolite concentrations vary due to common genetic variants encoding the biotransformation enzymes and environmental factors (e.g., concomitant drugs) that inhibit these enzymes. Effective treatment depends on adequate Tam conversion to its active isomers. To monitor metabolite plasma levels, a novel liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed to separate and quantitate Tam, N-desmethyl-tamoxifen (ND-Tam), and tamoxifen-N-oxide (Tam-N-oxide), and the E, Z, and Z' isomers of endoxifen and 4-OH-Tam. Known standards were used to identify each metabolite/isomer. Quantitation of these metabolites in plasma was linear from 0.6 to 2000 nM. Intra- and inter-assay reproducibilities were 0.2-8.4% and 0.6-6.3%, respectively. Accuracy determined by spike experiments with known standards was 86-103%. Endoxifen, 4-OH-Tam, and their isomers were stable in fresh frozen plasma for ≥6 months. This method provides the first sensitive, specific, accurate, and reproducible quantitation of Tam and its metabolite isomers for monitoring Tam-treated breast cancer patients.

Highlights of the Chemotherapy Foundation Symposium XXVII: therapeutic options for breast cancer.

The XXVII Annual Chemotherapy Foundation Symposium sponsored by The Mount Sinai School of Medicine is one of the leading forums for communication of important discoveries and new developments in cancer therapeutics. Here, we summarize and review the emerging advances in the treatment of breast cancer, which includes therapeutics in HER signaling, poly(ADP-ribose) polymerase inhibition, PI3K inhibitors and novel epithilones.

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.