Search results for "Alkylating"
showing 10 items of 66 documents
Trabectedin triggers direct and NK-mediated cytotoxicity in multiple myeloma
2019
Background Genomic instability is a feature of multiple myeloma (MM), and impairment in DNA damaging response (DDR) has an established role in disease pathobiology. Indeed, a deregulation of DNA repair pathways may contribute to genomic instability, to the establishment of drug resistance to genotoxic agents, and to the escape from immune surveillance. On these bases, we evaluated the role of different DDR pathways in MM and investigated, for the first time, the direct and immune-mediated anti-MM activity of the nucleotide excision repair (NER)-dependent agent trabectedin. Methods Gene-expression profiling (GEP) was carried out with HTA2.0 Affymetrix array. Evaluation of apoptosis, cell cyc…
Comparative analysis of the effects of a sphingosine kinase inhibitor to temozolomide and radiation treatment on glioblastoma cell lines.
2017
ABSTRACT Glioblastoma multiforme (GBM) exhibits high resistance to the standard treatment of temozolomide (TMZ) combined with radiotherapy, due to its remarkable cell heterogeneity. Accordingly, there is a need to target alternative molecules enhancing specific GBM autocrine or paracrine mechanisms and amplifying the effect of standard treatment. Sphingosine 1-phosphate (S1P) is such a lipid target molecule with an important role in cell invasion and proliferation. Sphingosine kinase inhibitors (SKI) prevent S1P formation and induce increased production of reactive oxygen species (ROS), which may potentiate radiation cytotoxicity. We analyzed the effect of SKI singular versus combined treat…
The cyto-protective effects of LH on ovarian reserve and female fertility during exposure to gonadotoxic alkylating agents in an adult mouse model.
2021
Abstract STUDY QUESTION Does LH protect mouse oocytes and female fertility from alkylating chemotherapy? SUMMARY ANSWER LH treatment before and during chemotherapy prevents detrimental effects on follicles and reproductive lifespan. WHAT IS KNOWN ALREADY Chemotherapies can damage the ovary, resulting in premature ovarian failure and reduced fertility in cancer survivors. LH was recently suggested to protect prepubertal mouse follicles from chemotoxic effects of cisplatin treatment. STUDY DESIGN, SIZE, DURATION This experimental study investigated LH effects on primordial follicles exposed to chemotherapy. Seven-week-old CD-1 female mice were randomly allocated to four experimental groups: C…
Schlafen-11 (SLFN11): a step forward towards personalized medicine in small-cell lung cancer?
2018
Purpose Both temozolomide (TMZ) and poly (ADP-ribose) polymerase (PARP) inhibitors are active in small-cell lung cancer (SCLC). This phase II, randomized, double-blind study evaluated whether addition of the PARP inhibitor veliparib to TMZ improves 4-month progression-free survival (PFS). Patients and Methods A total of 104 patients with recurrent SCLC were randomly assigned 1:1 to oral veliparib or placebo 40 mg twice daily, days 1 to 7, and oral TMZ 150 to 200 mg/m
Oral metronomic cyclophosphamide with and without methotrexate as palliative treatment for patients with metastatic breast carcinoma
2012
Oral metronomic chemotherapy is a therapeutic option which is particularly attractive due to its ease of administration and low toxic burden. Its mechanism of action probably involves antiangiogenetic effect rather than a classical antiproliferative effect like standard maximally tolerated dose-based regimens.A retrospective analysis of 61 patients with advanced breast carcinoma was carried out with the aim of reporting activity in terms of response rate, control of tumor-related symptoms, outcome, and toxicity. All patients had hormonal therapy-resistant metastatic disease and had previously received two lines of chemotherapy. The first cohort of 22 patients received oral cyclophosphamide …
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…
Busulfan systemic exposure after oral administration of extemporeanously prepared high-dose busulfan capsules.
2009
Purpose. The aim of the study was to analyze patients’ busulfan (BU) exposure after oral administration of extemporeanously prepared BU capsules prior to blood stem cell transplantation. Methods. Patients were treated with 1 mg/kg body weight BU administered orally every 6h on each of 4 consecutive days prior to blood stem cell transplantation. Each BU dose was administered in 1 gelatine capsule to be swallowed and containing the individually calculated dose of pure BU active substance. Blood samples were obtained from 6 adult patients 0, 30, 60, 90, 120, 180, 240, 300, and 360 min after the 1st, 5th, and 13th BU dose, frozen and analyzed subsequently by using a HPLC assay with UV detectio…
Chemoradiotherapy of Newly Diagnosed Glioblastoma With Intensified Temozolomide
2009
Purpose To evaluate the toxicity and efficacy of chemoradiotherapy with temozolomide (TMZ) administered in an intensified 1-week on/1-week off schedule plus indomethacin in patients with newly diagnosed glioblastoma. Patients and Methods A total of 41 adult patients (median Karnofsky performance status, 90%; median age, 56 years) were treated with preirradiation TMZ at 150 mg/m 2 (1 week on/1 week off), involved-field radiotherapy combined with concomitant low-dose TMZ (50 mg/m 2 ), maintenance TMZ starting at 150 mg/m 2 using a 1-week on/1-week off schedule, plus maintenance indomethacin (25 mg twice daily). Results The median follow-up interval was 21.7 months. Grade 4 hematologic toxicit…
Body Mass Index as a Risk Factor for Toxicities in Patients with Advanced Soft-Tissue Sarcoma Treated with Trabectedin
2017
<b><i>Objectives:</i></b> Low body mass index (BMI) and/or low lean body mass have been shown to be risk factors for chemotherapy-related toxicities in a number of different cancers. However, no data are available regarding the role of BMI as a risk factor for developing toxicities related to the novel anticancer agent, trabectedin, in patients with soft-tissue sarcoma (STS). We evaluated the role of BMI as a risk factor for trabectedin-related toxicity in patients with STS. <b><i>Methods:</i></b> Data from 51 patients with metastatic/advanced STS treated with trabectedin after progression on ≥1 anthracycline ± ifosfamide regimen were retrospe…
MGMT promoter methylation status and prognosis of patients with primary or recurrent glioblastoma treated with carmustine wafers
2013
The prognostic role of O(6)-methylguanine-DNA methyltransferase (MGMT) promoter methylation in glioblastoma patients treated with carmustine (BCNU) wafer implantation is unclear. Here, we report on a retrospective study of 47 patients with either newly diagnosed (30 patients) or recurrent (17 patients) glioblastoma (WHO grade IV) treated with BCNU (bis-chloroethylnitrosourea) wafers. Thirteen of the newly diagnosed patients received local BCNU and irradiation only (first-line BCNU), while 17 patients additionally received concomitant and adjuvant temozolomide (TMZ) radiochemotherapy (first-line BCNU + TMZ). Of the 17 patients treated for recurrent glioblastoma (second-line BCNU), 16 had rec…