LXR/ApoE Activation Restricts Innate Immune Suppression in Cancer.

Therapeutic harnessing of adaptive immunity via checkpoint inhibition has transformed the treatment of many cancers. Despite unprecedented long-term responses, most patients do not respond to these therapies. Immunotherapy non-responders often harbor high levels of circulating myeloid-derived suppressor cells (MDSCs)-an immunosuppressive innate cell population.

JAK inhibition with ruxolitinib versus best available therapy for myelofibrosis.

Background: Treatment options for myelofibrosis are limited. We evaluated the efficacy and safety of ruxolitinib, a potent and selective Janus kinase (JAK) 1 and 2 inhibitor, as compared with the best available therapy, in patients with myelofibrosis.

Methods: We assigned 219 patients with intermediate-2 or high-risk primary myelofibrosis, post-polycythemia vera myelofibrosis, or post-essential thrombocythemia myelofibrosis to receive oral ruxolitinib or the best available therapy.

High rates of durable response are achieved with imatinib after treatment with interferon alpha plus cytarabine: results from the International Randomized Study of Interferon and STI571 (IRIS) trial.

Background: Imatinib is the standard of care for newly diagnosed chronic-phase chronic myeloid leukemia. The largest randomized clinical trial of imatinib was the multinational IRIS trial in which 1106 patients were randomized to receive either imatinib 400 mg/day or a standard regimen of interferon-alpha plus cytarabine.

Design And Methods: Patients were allowed to cross over to the opposite treatment for intolerance, lack of response, disease progression, and, following release of the initial efficacy data, reluctance to remain on therapy with interferon-alpha plus cytarabine.

A pilot study to evaluate the safety and clinical outcomes of once-weekly epoetin alfa 80,000 u in anemic patients with cancer receiving chemotherapy.

Background: Epoetin alfa is indicated for the treatment of chemotherapy-induced anemia at doses of 150 U/kg 3 times weekly or 40,000 U once weekly. Higher starting doses may lead to higher hematologic response rates (RRs), earlier hematologic responses, and earlier identification of nonresponders. The hematologic response and safety of epoetin alfa at a starting dose of 80,000 U once weekly in anemic patients (hemoglobin [Hb] View Article and Find Full Text PDF

Invasive anal squamous-cell carcinoma in the HIV-positive patient: outcome in the era of highly active antiretroviral therapy.

Introduction: The incidence of invasive anal squamous-cell carcinoma in patients with HIV is increasing. We report the outcome after combined chemoradiotherapy for anal squamous-cell carcinoma in HIV-infected individuals.

Methods: Thirty-two HIV-positive patients treated at the St.

Communicating about chemotherapy-induced anemia.

Many validated instruments exist for determining the impact of chemotherapy-induced anemia and related fatigue on patient quality of life, but few studies analyze how healthcare providers actually discuss these subjects with patients. The authors share their study results on patterns of communication between participating patients and their physicians and allied health professionals. Letters of invitation were mailed to over 1,000 community-based oncologists, 15 of whom met the criteria and agreed to participate in this study on a first-enrolled basis until sufficient participation was ensured.

Randomized comparison of epoetin alfa (40,000 U weekly) and darbepoetin alfa (200 microg every 2 weeks) in anemic patients with cancer receiving chemotherapy.

This is the first randomized, open-label, multicenter trial designed and powered to directly compare the hemoglobin (Hb) response to epoetin alfa (EPO), 40,000 U once weekly (QW), with that to darbepoetin alfa (DARB), 200 microg every 2 weeks (Q2W), in anemic patients with cancer receiving chemotherapy (CT). Transfusion requirements, quality of life (QOL), and safety also were evaluated. Adults with solid tumors scheduled to receive CT for > or =12 weeks and with baseline Hb < or =11 g/dl were randomized to receive either EPO 40,000 U QW (n = 178) or DARB 200 microg Q2W (n = 180) s.

Assessing the clinical benefits of erythropoietic agents using area under the hemoglobin change curve.

Introduction: In assessing erythropoietic agents for chemotherapy-induced anemia, traditional single time-point end points (e.g., hematopoietic response [HR]) fail to reflect clinical benefits over the entire therapy course.

Treatment of chemotherapy-related anemia with erythropoietic agents: current approaches and new paradigms.

Anemia is common among patients with cancer receiving chemotherapy (CT) and/or radiotherapy (RT) and may limit cancer treatment, clinical outcomes, and overall patient quality of life (QOL). In the United States, epoetin alfa and darbepoetin alfa are approved for the treatment of CT-induced anemia in patients with nonmyeloid malignancies. Goals of treatment are to reduce transfusions, increase hemoglobin (Hb) levels, and improve overall QOL.

Managing hematologic toxicities.

This overview of the hematologic toxicities of cancer chemotherapy addresses the frequency and clinical significance of neutropenia, anemia, and thrombocytopenia and attempts to provide evidence-based guidelines, based on clinical trials, for the use of cytokine growth factors and transfusion support. The current emphasis on high-dose and dose-dense chemotherapy increases the need for close attention to the amelioration ofhematologic toxicities. The latter is highly dependent upon the appropriate and judicious use of cytokine support.

Identification of risk factors for requiring transfusion during front-line chemotherapy for ovarian cancer.

Objective: Anemia requiring red blood cell (RBC) transfusion is common in ovarian cancer (OC) patients receiving post-debulking surgery chemotherapy. Erythropoietin use has been shown to decrease transfusion requirements in patients receiving chemotherapy. We sought to identify pretreatment risk factors that could identify patients at increased risk for requiring RBC transfusion during first-line treatment for ovarian cancer.

Primary intravenous paclitaxel and platinum chemotherapy for high-risk Stage I epithelial ovarian carcinoma.

Objective: To evaluate the efficacy of intravenous (i.v.) paclitaxel and platinum chemotherapy in patients with high-risk Stage I epithelial ovarian carcinoma.

Phase II trial of paclitaxel in patients with soft-tissue sarcoma.

The response rate (RR) to single-agent chemotherapy with doxorubicin or ifosfamide in patients with advanced soft-tissue sarcoma (STS) is in the range of 20%. Paclitaxel is clinically useful in treating several solid tumors and has demonstrated activity in a series of human sarcoma cell lines. Twenty-eight patients with measurable advanced STS participated in this phase II trial of paclitaxel at 250 mg/m2 administered as a 3-hr i.

Phase II study of "dose-dense" high-dose chemotherapy treatment with peripheral-blood progenitor-cell support as primary treatment for patients with advanced ovarian cancer.

Purpose: We performed a pilot phase II study to evaluate the potential for delivery of rapidly sequenced high-dose chemotherapy treatments rescued with autologous peripheral-blood progenitor cells (PBP) in patients with previously untreated, advanced ovarian cancer.

Patients And Methods: A single cycle of mobilization was used, primed with cyclophosphamide (CPA)/paclitaxel (Txl) and filgrastim (granulocyte colony-stimulating factor [G-CSF]), followed by three cycles of high-dose carboplatin (CBDCA)/Txl and one cycle of high-dose melphalan (MEL), each rescued by PBP. We then analyzed the outcome for a total of 56 consecutive patients treated with high-dose chemotherapy as part of this program.