Search results for "Toxicity"

Phase II Study of Taselisib (GDC-0032) in Combination with Fulvestrant in Patients with HER2-Negative, Hormone Receptor–Positive Advanced Breast Canc…

2018

AbstractPurpose: This single-arm, open-label phase II study evaluated the safety and efficacy of taselisib (GDC-0032) plus fulvestrant in postmenopausal women with locally advanced or metastatic HER2-negative, hormone receptor (HR)-positive breast cancer.Patients and Methods: Patients received 6-mg oral taselisib capsules daily plus intramuscular fulvestrant (500 mg) until disease progression or unacceptable toxicity. Tumor tissue (if available) was centrally evaluated for PIK3CA mutations. Adverse events (AE) were recorded using NCI-CTCAE v4.0. Tumor response was investigator-determined using RECIST v1.1.Results: Median treatment duration was 4.6 (range: 0.9–40.5) months. All patients expe…

Dose intensification of mitoxantrone in combination with levofolinic acid, fluorouracil, cyclophosphamide and granulocyte colony stimulating factor s…

1997

Fifty-five consecutive patients with metastatic breast cancer (MBC) (n = 57) were treated with a combination of levofolinic acid (I-FA) 100 mg/m2 plus 5-fluorouracil (5-FU) 340 mg/m2 i.v. on day 1-3, cyclophosphamide (CTX) 600 mg/m2 i.v. on day 1 and mitoxantrone (DHAD) 12 mg/m2 i.v. on day 1. DHAD dose was progressively escalated by 2 mg/m2/cycle up to 18 mg/m2 in the absence of dose-limiting toxicities. Granulocyte colony stimulating factor (G-CSF) was given s.c. in order to prevent neutropenia. DHAD dosage could be increased to 18 mg/m2 in 66 out of 317 cycles of chemotherapy (21%). In most patients the dose-limiting toxicity was represented by myelosuppression. A statistically significa…

Increased frequency of proinflammatory CD4 T cells and pathological levels of serum neurofilament light chain in adult drug-resistant epilepsy

2020

OBJECTIVE: Adult drug-resistant epilepsy (DRE) is associated with significant morbidity. Infiltration of immune cells is observed in DRE epileptic foci; however, the relation between DRE and the peripheral immune cell compartment remains only partially understood. We aimed to investigate differences in immune cell populations, cytokines, and neurodegenerative biomarkers in the peripheral blood of subjects with epilepsy versus healthy controls, and in DRE compared to well-controlled epilepsy (WCE). METHODS: Peripheral blood mononuclear cells and serum from >120 age- and sex-matched adults suffering from focal onset epilepsy and controls were analyzed by multipanel flow cytometry, multiplex i…

Potential involvement of IL-22 and IL-22-producing cells in the inflamed salivary glands of patients with Sjogren's syndrome.

2012

OBJECTIVES: In chronic inflammatory disorders, interleukin (IL)-22 may act either as a protective or as a pro-inflammatory cytokine. At mucosal sites, IL-22 is mainly produced by CD4(+) T cells and by a subset of mucosal natural killer (NK) cells expressing the receptor NKp44 (NKp44(+) NK cells). The aim of this study was to investigate the IL-22 expression in the salivary glands of patients with primary Sjögren's syndrome (pSS). METHODS: Minor salivary gland biopsies were obtained from 19 patients with pSS and 16 with non-specific chronic sialoadenitis. Quantitative gene expression analysis by TaqMan real-time PCR and immunohistochemistry for IL-17, IL-22, IL-23 and STAT3 (signal transduce…

Weekly administration of gemcitabine plus docetaxel in patients with advanced breast cancer: a phase 1 study.

2002

<i>Objective:</i> This study was designed to determine the maximum tolerable dose (MTD) of gemcitabine plus docetaxel, both given on a weekly schedule, in patients with pretreated metastatic breast cancer (MBC). <i>Methods:</i> Heavily pretreated patients with MBC, aged 18–75 years with World Health Organization performance status of 0–2 were enrolled. Three escalating weekly doses of docetaxel (30, 35 and 40 mg/m<sup>2</sup>) followed by a weekly fixed dose of gemcitabine, 800 mg/m<sup>2</sup>, were administered on days 1, 8 and 15 of a 28-day cycle. Dose-limiting toxicity (DLT) included grade >3 hematologic toxicity and grade >2 stomat…

Cis-diamminodichloroplatinum plus a 5-day continuous infusion of 5-fluorouracil in the treatment of locally recurrent and metastatic head and neck ca…

1989

A group of 23 consecutive patients with biopsy-proven advanced or metastatic head and neck cancer were treated with cisplatinum, 100 mg/m2 i.v., on day 1 plus 5-fluorouracil, 1000 mg/m2, in continuous infusion for 5 days. Most patients (87%) had recurrent or metastatic cancer and were previously treated (78%). Out of 21 evaluable patients we obtained a 42% overall response rate (complete + partial responses) with a mean duration of more than 8 months and a 14% minimal response rate. A stabilization of disease was achieved in 28% of cases, while 14% of patients progressed. This response rate, as well as the duration of response, seems to be similar to those obtained in other series comprisin…

Acute effects on the human EEG after an external exposure to 200 ppm methanol

2001

Objectives: Even low concentrations of organic solvents may cause acute effects on the human central nervous system. The German MAK (threshold limit value) of methanol is 200 ppm. The aim of this study was to investigate whether acute exposure to 200 ppm methanol causes adverse effects, measured by EEG, and moreover, whether it is possible to differentiate between sedative and excitatory effects with this method. Methods: Twelve healthy subjects were exposed for 4 h to 200 ppm and to 20 ppm (control) in an exposure chamber in a cross-over design. The EEG was recorded before (reference) and at the end of each exposure with, the subject's eyes closed and opened and during a choice reaction te…

Antibodies to vascular endothelial cells in chronic rejection of renal allografts.

2000

Clonal analysis of liver-infiltrating T cells in patients with LKM-1 antibody-positive autoimmune chronic active hepatitis

1991

SUMMARY Autoantibodies against microsomal antigen of liver and kidney (LKM-1) are diagnostic markers for a subgroup of autoimmune chronic active hepatitis (AI-CAH). Cytochrome P4S0dbl, now classified as cytochrome P450 IID6, is the major antigen of LKM-1 antibodies. Immunohistological studies suggest that hepatic injury in AI-CAH is mediated by liver-infiltrating T cells. In the present study the specificity and function of liver-infiltrating T cells was analysed at the clonal level. Phenotypical characterization of 189 T cell clones isolated from four liver biopsies of LKM-1 antibody-positive patients showed an enrichment of CD4+CD8- T cells. Five CD4+CD8- T cell clones proliferated specif…

Phase I study in melanoma patients of a vaccine with peptide-pulsed dendritic cells generated in vitro from CD34(+) hematopoietic progenitor cells.

2000

Dendritic cells (DCs) are professional antigen-presenting cells (APCs) that can be used for vaccination purposes, to induce a specific T-cell response in vivo against melanoma-associated antigens. We have shown that the sequential use of early-acting hematopoietic growth factors, stem cell factor, IL-3 and IL-6, followed by differentiation with IL-4 and granulocyte-macrophage colony-stimulating factor allows the in vitro generation of large numbers of immature DCs from CD34(+) peripheral blood progenitor cells. Maturation to interdigitating DCs could specifically be induced within 24 hr by addition of TNF-alpha. Here, we report on a phase I clinical vaccination trial in melanoma patients us…