Gina Villani

Chemotherapy in the Elderly: Pharmacologic Considerations

BACKGROUND The aging of the population has focused interest on the care of elderly cancer patients. A better understanding of the effects of chemotherapeutic agents on older patients with cancer will help to determine the appropriate use of chemotherapy for this age group. METHODS The authors review recent studies and present pharmacokinetic data on several chemotherapeutic agents, particularly those that have recently become available. RESULTS Agents such as gemcitabine, vinorelbine, the taxanes, anthracyclines, platinum compounds, topoisomerase I and II inhibitors, and the oral fluoropyrimidines appear to have a beneficial therapeutic index in elderly patients. CONCLUSIONS Careful attention to the physiologic changes associated with aging, along with dose adjustments for end-organ dysfunction (eg, renal and hepatic), is necessary to ensure the safe administration of antitumor chemotherapy to the elderly.

Addressing Obesity and Diabetes Among African American Men: Examination of a Community-Based Model of Prevention

The Save Our Sons study is a community-based, culturally responsive, and gender-specific intervention aimed at reducing obesity and diabetes among a small sample (n = 42) of African American men. The goals of the study were to: (1) test the feasibility of implementing a group health education and intervention model to reduce the incidence of diabetes and obesity among African American men; (2) improve regular access to and utilization of health care services and community supportive resources to promote healthy lifestyles among African American men; and (3) build community networks and capacity for advocacy and addressing some of the health needs of African American men residing in Lorain County, Ohio. Trained community health workers facilitated activities to achieve program aims. Following the 6-week intervention, results indicated that participants had greater knowledge about strategies for prevention and management of obesity and diabetes; increased engagement in exercise and fitness activities; decreased blood pressure, weight, and body mass index levels; and visited a primary care doctor more frequently. Also, local residents elevated African American mens health and identified it as a priority in their community. This model of prevention appears to be a substantial, robust, and replicable approach for improving the health and wellbeing of African American men.

American Society of Clinical Oncology Policy Statement on Medicaid Reform

Blase N. Polite, University of Chicago, Chicago, IL; Jennifer J. Griggs and Sandra L. Wong, University of Michigan, Ann Arbor, MI; Beverly Moy, Massachusetts General Hospital; Christopher Lathan, Dana-Farber Cancer Institute, Boston, MA; Nefertiti C. duPont, Roswell Park Cancer Institute, Buffalo; Gina Villani, Ralph Lauren Center for Cancer Care and Prevention, New York, NY; and Michael T. Halpern, RTI International, Washington, DC.

Effectiveness of radiation therapy in GIST: A case report

Over the last decade, gastrointestinal stromal tumor (GIST) became the most commonly diagnosed mesenchymal tumor of the gastrointestinal tract (2,3)Population-based studies suggest an annual incidence of between 11 and 14.5 per million and a prevalence of 129 per million (8). The immunohistochemistry of GIST shows the presence of cellsurface antigen CD117 (KIT), which represents a defining characteristic of GIST (4-7). Immunostaining is essential to differentiate GISTs from other more rare mesenchymal tumors. Differential diagnosis includes leiomyosarcomas, leiomyomas and schwannomas (8). It is believed that GISTs arise from a neoplastic transformation of the intestinal pacemaker cells known as the interstitial cells of Cajal (ICC) (6,9). Prior to 2002, the only available therapeutic option for patients with localized GISTs was surgical resection (10). Unfortunately, even when excised in negative surgical margins, the recurrence rate for lesions larger than 3 cm was found to be significant. Introduction of the first tyrosine k inase inhibitor, imatinib mesylate, has dramatical ly changed the management options avai lable for GIST patients (11). The role of radiation therapy in the treatment of GISTs has not been documented (12). In the past, clinicians were reluctant to use radiation therapy due to concerns over the dose received by normal tissues, mostly the potential gastrointestinal toxicity. As such, radiation therapy has been uti l ized rarely, mostly for pall iation purposes (13). In this report, we describe the successful use of intensity modulated radiation therapy to treat an individual with large intra-abdominal GIST lesions (Figure 1), which were deemed unresectable. An initial attempt at systemic treatment with imatinib was not tolerated by the patient and did not produce a significant response.

A novel second line chemotherapy treatment of recurrent thymoma

Thymoma is an uncommon malignancy which is initially treated with surgery. Combined modality treatment with radiation and chemotherapy is utilized in cases of unresectable or metastatic disease. In patients with relapse, a number of different chemotherapeutic regimens have been used with varying success. The case of a male with recurrent thymoma treated with carboplatin and paclitaxel is presented and the literature reviewed. The patient responded to this novel regimen with improvement in clinical symptoms and reduction in tumor mass. This novel regimen has shown activity as second line therapy and merits further investigation as a first line treatment for patients with invasive and or metastatic thymoma.

A rare case of intracerebral hemorrhage complicating heparin-induced thrombocytopenia with thrombosis: a clinical dilemma ameliorated by novel use of plasmapheresis

We report a case of heparin-induced thrombocytopenia with thrombosis type 2 (HITT 2) that was first complicated by intracerebral hemorrhage (ICH) and later by deep venous thrombosis (DVT). HITT 2 was initially managed conventionally with argatroban, which was stopped when ICH was discovered. The size of ICH increased despite attempts to increase platelet count by platelet transfusions. At this point of the clinical dilemma, plasma exchange was utilized effectively to recover the platelet count and deter ICH progression. The clinical course was later complicated by DVT, for which fondaparinux was given. This case represents a rare clinical scenario of HITT 2 resulting in progressive ICH that excluded the use of antithrombotic agents as part of HITT therapy. We believe that the use of plasmapheresis as a salvage procedure in such situations is effective and life-saving. Physicians should be aware of plasmapheresis as a therapeutic option in HITT 2 in cases in which anticoagulation is contraindicated.

Potential of the Patient Protection and Affordable Care Act to Reduce Cancer Care Disparities

Although the Patient Protection and Affordable Care act provides some means to reduce disparities in cancer care, it may also have unintended consequences. Oncologists must go beyond its provisions to ensure quality care for all patients.

Thrombotic thrombocytopenic purpura complicating immune thrombocytopenic purpura—A case report

To the editor: A 60-year-old male was evaluated for episodes of gingival bleed. Past medical history was significant for hypertension currently treated with clonidine and aliskiren and early stage prostate cancer. Social and family histories were noncontributory. Review of systems was negative except for bleeding. Physical examination was unremarkable. Platelet count was 8 3 10/l and peripheral smear demonstrated thrombocytopenia with few large platelets. Immune Thrombocytopenic Purpura (ITP) was diagnosed, and the patient was treated with prednisone 40 mg/day with significant improvement in his platelet count. Prednisone was then tapered to 5 mg/day. Six months later, the patient developed gingival bleed, chest pain, shortness of breath, and hematuria. Physical examination revealed elevated blood pressure (200/104 mm of Hg), gingival bleeding, and a hematoma of the tongue. Laboratory tests showed platelet count 6 3 10/l, Lactate Dehydrogenase (LDH) 1348 u/l, Antinuclear Antibody (ANA) titers 1:160, and total bilirubin 6 mg/dl. Coagulation profile, hepatitis panel, Thyroid-stimulating hormone (TSH), Human immunodeficiency virus (HIV), Rh factor, and direct antiglobulin test were negative. The diagnosis of ITP, myocardial infarction, and uncontrolled hypertension was made. Prednisone was increased to 60 mg/day, and blood pressure control was optimized. On admission Day 2, the patient developed altered mental status and fever. Computerized Axial Tomography (CAT) scan of head revealed intracranial bleed. His hemoglobin level fell by 2 g/dl and serum creatinine increased. Peripheral smear confirmed the diagnosis of Thrombotic Thrombocytopenic Purpura (TTP). Plasmapheresis was initiated, mental status returned to baseline, and renal function remained stable. ADAMTS -13 (Is a metalloproteinase also known as von Willebrand factor-cleaving Protease) activity obtained before plasmapheresis was 12%, and von Willebrand factor cleaving inhibitor level was 1.4 (normal less than 0.4). Plasmapheresis was continued for 12 exchanges with modest recovery of platelet count from. The patient remained anemic, LDH levels remained high, and 21 schistocytes persisted on peripheral blood smear. Therapy with rituximab (4 weekly doses of 375 mg/m), methylprednisone (1 mg/kg/day) and intravenous immunoglobulin G was initiated. After the fourth course of this regimen, the platelet count was 107 3 10/L, LDH levels decreased, the hematocrit remained stable, and peripheral smear showed no fragmented red blood cells. The patient was successfully tapered off prednisone and has remained well. TTP and ITP existing in the same patient are uncommon. Seventeen cases have been reported in the literature with both conditions occurring at different times or concurrently (only one case). Baron et al. [1] reviewed 11 cases of TTP, six of which had an underlying autoimmune disorder. Baron suggested that these six cases represented a distinct clinical syndrome, ‘‘mixed immune thrombocytopenia,’’ due to disturbed immune regulation. Our patient initially presented with isolated thrombocytopenia and positive ANA titers suggestive an immune-mediated disease that responded transiently to steroids. On readmission, he was diagnosed with TTP and started on appropriate therapy with good clinical outcome. In conclusion, emphasis should be placed on a thorough re-evaluation of each recurrence of thrombocytopenia. Overlapping of these two distinct clinical entities may be misleading and can delay appropriate treatment. As evidenced by existing literature, the patient who presents with an initial episode of either ITP or TTP, may subsequently present with either of these syndromes at relapse.

Phase II trial of infusional cyclophosphamide, idarubicin, and etoposide in poor prognosis non-Hodgkin's lymphoma

The purpose of this study was to determine the complete response (CR) rate, failure-free survival (FFS), and overall survival (OS) of patients with poor-prognosis intermediate-grade non-Hodgkin’s lymphoma (NHL) after treatment with cyclophosphamide, idarubicin, and etoposide given as a continuous intravenous infusion (CIVI) over 96 hours (infusional CIE), including patients with relapsed/refractory disease and patients with no prior therapy but at least two poor-risk features by the age-adjusted International Prognostic Index. Forty-two patients with previously untreated NHL (N = 24) or relapsed/refractory (N = 18) NHL received cyclophosphamide (200 mg/m2/d), idarubicin (2.5–3.0 mg/m2/d) and etoposide (60 mg/m2/d) given by a 96-hour CIVI every 3 weeks for a maximum of 8 cycles. All patients also received granulocyte–colony-stimulating factor. CR occurred in 10 of 24 patients (42%; 95% confidence intervals [CI] 22%, 62%) treated with CIE as first-line therapy, and in 3 of 18 patients (17%; 95% CI 20%, 32%) treated with CIE as second-line or greater therapy. One-year FFS and OS were 42% and 64%, respectively, in patients with no prior therapy, and 17% and 56% in patients with prior therapy. Severe (grade III) or life-threatening (grade IV) toxicity included leukopenia (59%), anemia (61%), thrombocytopenia (31%), and infection (10%). Two patients (4%) died due to treatment related infectious complications. It is unlikely that infusional CIE produces a CR rate more than about 60% in poor-risk patients with intermediate-grade NHL when used as first-line therapy, or more than about 30% in patients receiving the regimen as second-line therapy. Substitution of idarubicin for doxorubicin in this setting, therefore, is not associated with an improved response rate.

Gender differences in colorectal cancer in downtown Brooklyn, New York.

e12002 Background: Colorectal cancer (CRC) is the second leading cause of cancer mortality in the United States. CRC is more common in males than in females. Surveillance, Epidemiology and End Results (SEER) incidence for 2003-2007 showed 55.8 per 100000 male colorectal cancers versus 41.7 colorectal cancers per 100000 females. However, tumor registry data from our hospital for the year 2008 showed a female predominance in colorectal cancer incidence. The objective of this study was to evaluate the trends in colorectal cancer incidence, age and stage at initial presentation in a community hospital over a period of five years, with a special emphasis on gender difference in CRC. Ethnicity, median age at diagnosis and stage of the disease at the time of diagnosis is also examined. METHODS A retrospective review of all colorectal cancers diagnosed at the Brooklyn Hospital Center over a five-year period was undertaken. Information regarding gender, race, age and stage at diagnosis was analyzed. RESULTS Of the 403 patients with colorectal cancer, 323 patients (80.14%) were African American. Of these, 163 patients (40.4 %) were males and 240 patients (59.6 %) were females. Distant metastatic disease at presentation was seen in 19% of the patients and majorities (74%) were older than 60 years. CONCLUSIONS Contrary to SEER data, fewer men than women were diagnosed with colorectal cancer at our institution. In general, studies have shown that women tend to receive CRC screening test less often than men. It is possible that CRC screening uptake may have been even lower in underserved Brooklyn female population. We postulate that these differences signify inadequate and ineffective screening for CRC in women living in Brooklyn rather than a true biologic trend. Until definitive data regarding gender difference in minorities are available, our data supports aggressive screening programs geared towards females, especially among minority population. More studies are needed examining gender differences to identify subgroup population who consistently underuse CRC screening for future interventions.