Publications by authors named "Plezia P"

Article Synopsis
  • Bevacizumab, a drug that inhibits VEGF-A, combined with chemotherapy has shown improved survival rates for patients with metastatic colorectal cancer (mCRC), but researchers are exploring another dual-blocker, vanucizumab, which targets both VEGF-A and angiopoietin-2 (Ang-2).
  • In a phase II trial, 189 patients received either vanucizumab plus modified FOLFOX-6 chemotherapy or bevacizumab plus the same chemotherapy, with progression-free survival (PFS) as the main outcome measure.
  • Results indicated that both treatments had similar PFS outcomes and safety profiles, with favorable response rates, but vanucizumab did not show significant advantages over bevacizumab
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Purpose: To perform a phase I and pharmacokinetics study of 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP) a new ribonucleotide reductase inhibitor using a single intravenous (2-h) schedule every 4 weeks. 3-AP was given at a starting dose of 5 mg/m(2) with escalation based on a modified Fibonacci scheme.

Patients And Methods: A total of 27 patients with advanced cancer were entered into the study.

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Dolasetron mesylate (MDL 73,147, Anzemet, Hoechst Marion Roussel, Kansas City, MO) is a 5-HT ( 3 ) receptor antagonist undergoing clinical evaluation as an antiemetic agent. Dolasetron is rapidly metabolized to form hydrodolasetron (MDL 74,156). The pharmacokinetics of hydrodolasetron were studied after administration of a single intravenous infusion of 0.

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This randomized, double-blind, parallel-group, multicenter study compared the antiemetic effectiveness, safety, and tolerability of two different intravenous (i.v.) doses of dolasetron mesylate (0.

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Purpose: To determine the maximally tolerated dose of mitoxantrone in combination with cytarabine in patients with acute leukemia and advanced phases of chronic myelogenous leukemia (CML), and to assess the pharmacokinetics of high-dose mitoxantrone in this patient population.

Patients And Methods: In a phase I study, 68 patients with acute myelogenous leukemia (AML), acute lymphoblastic leukemia (ALL), and accelerated- and blastic-phase CML received induction therapy consisting of cytarabine 3 g/m2 by infusion over 3 hours daily for 5 days, with escalating doses of mitoxantrone 40 to 80 mg/m2 over 1 to 2 days by intravenous infusion over 15 minutes. Mitoxantrone pharmacokinetics were evaluated by high-performance liquid chromatography (HPLC) in 15 patients given a single dose of mitoxantrone ranging from 40 to 80 mg/m2 in combination with cytarabine.

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Background: Sulofenur is a diarylsulfonylurea with demonstrated antitumor activity in patients with advanced epithelial ovarian cancer refractory to standard chemotherapy. The dose-limiting toxic effects observed in phase I clinical trials have been anemia and methemoglobinemia, resulting in cyanosis.

Purpose: The purposes of this study were to further define the response rate, toxic effects, and pharmacokinetics and pharmacodynamics of sulofenur in patients with advanced ovarian cancer.

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Background: Beta-carotene is one of the most commonly used compounds in clinical trials of chemopreventive agents in various neoplastic diseases. Animal studies, including our own, have documented that dietary beta-carotene can reduce plasma alpha-tocopherol (vitamin E) levels, but few published studies have examined the clinical or pharmacokinetic ramifications of long-term, high-dose beta-carotene regimens on other fat-soluble vitamins such as alpha-tocopherol.

Purpose: This study was designed to determine the effects of long-term beta-carotene supplementation on plasma concentrations of alpha-tocopherol in normal human subjects and in an experimental C3H/HeN mouse model.

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We previously reported that cimetidine but not ranitidine significantly enhances cyclophosphamide-induced bone marrow toxic effects and the appearance of cyclophosphamide alkylating species in a murine leukemia mouse model, and we advised caution in the use of cimetidine with microsomally metabolized anticancer drugs. Both drugs have been used for the treatment of gastric complications of chemotherapy. Using a randomized, double-blind, crossover study design, we have now evaluated the potential interaction of ranitidine with cyclophosphamide in seven cancer patients, who received two courses of cyclophosphamide, one with ranitidine and one with placebo.

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Verapamil was evaluated as a chemosensitizer for reversing multidrug resistance in multiple myeloma both in vitro and in clinical trials. Bone marrows from 59 myeloma patients in relapse were evaluated for several resistance parameters: expression of p-glycoprotein (MDR1), doxorubicin (Adriamycin) and vincristine sensitivity, and the ability of added verapamil to reduce resistance to the cytotoxic agents. We found that verapamil was capable of sensitizing myeloma cells that exhibited resistance to doxorubicin and vincristine in vitro, but did not enhance sensitivity of cells that were drug sensitive (P less than .

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Based on clinical evidence that prolonged exposure to anti-neoplastic agents may ameliorate dose-limiting toxicity while facilitating anti-tumor activity, we conducted a phase I trial of 14-day continuous intravenous infusion mitoxantrone. Study objectives were to: (1) determine the maximally tolerated dose for phase II trials; (2) determine the incidence and severity of side effects; and (3) study the pharmacokinetics of continuous infusion mitoxantrone. Sixteen patients with drug-resistant advanced cancers were entered into the trial.

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Aside from its more conventional uses as a cardiovascular drug, the calcium channel blocker verapamil has recently been added to chemotherapeutic regimens to reduce drug resistance in B-cell and other neoplasms that express the P-glycoprotein. We recently treated patients with continuous-infusion verapamil (0.15 mg/kg per hour to 0.

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The effects of various doses (0, 15, 30, 45, and 60 mg/d) of supplementary beta-carotene were evaluated. The percentage of lymphoid cells with surface markers for T-helper and natural killer (NK) cells and cells with interleukin 2 (IL-2) and transferrin receptors were significantly and substantially increased in peripheral blood mononuclear cells collected from older human adult volunteers after supplementation with greater than or equal to 30 mg beta-carotene/d for 2 mo. The increase in the percentage of cells with markers of NK cells and in expression of IL-2 receptors was dose dependent.

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In a randomized open crossover study, the antiemetic efficacy of a five-drug antiemetic regimen consisting of metoclopramide, dexamethasone, diazepam, diphenhydramine, and thiethylperazine was compared to that of high-dose metoclopramide. Thirteen patients treated with cisplatin combination chemotherapy regimens were evaluated. The study was terminated prior to accrual of the planned number of patients because of the statistically significant difference in efficacy between treatments found at interim analysis.

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The semi-synthetic vinca alkaloid vinzolidine was administered to advanced cancer patients as an intravenous bolus on a three day schedule every 21 days. Forty-two patients were treated in this phase I trial. Five partial remissions (breast--1, melanoma--2, renal cancer--2) were seen in 30 evaluable patients.

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Plasma vitamin K concentrations and prothrombin coagulation activity were determined in 26 normal adults who had received daily beta-carotene supplementation (0, 15, 30, or 60 mg) for six months. Neither plasma vitamin K nor coagulation activity were significantly decreased at any supplementation level. Thus, chronic beta-carotene supplementation, even at high daily doses, is not expected to result in clinical vitamin K deficiency.

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In a randomized, crossover study the influence of enteral feedings (Ensure) on the absorption of theophylline from a sustained-release preparation (Theo-24) was evaluated. Six healthy, male subjects, age 22 to 37 years, participated. In phase 1 the subjects received a single oral dose of Theo-24 6 mg/kg with 100 ml of water at 8:00 A.

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LY186641 (diarylsulfonylurea, [DSU]) is a novel anticancer agent because of its unique diarylsulfonylurea chemical structure, broad-spectrum antisolid-tumor activity in preclinical models, presumed novel mechanism of action and preclinical toxicities of methemoglobinemia (Met Hgb) and decreased red blood cell (RBC) survival. In this study, the in vitro drug sensitivity of human tumors as well as clinical pharmacology and toxicology of DSU in patients with cancer were examined. DSU was administered orally, daily for 7 days with a 3-week treatment cycle.

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Theophylline disposition was examined in seven passive smokers, defined as nonsmokers with long-term exposure to cigarette smoke, and seven age-matched nonsmokers with minimal smoke exposure. Subjects were given an intravenous infusion of aminophylline (6 mg/kg) and blood samples were drawn before and during the 48-hour postinfusion period. Clearance for passive smokers was 6.

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The design and interpretation of chemoprevention trials are challenging tasks. Innovative methodological approaches to these investigations are in initial stages of development. Important pharmacologic issues should be addressed as early as possible in these trials to facilitate the optimal design of large, Phase III, randomized trials.

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A new transdermal drug-delivery system that administers the synthetic opioid fentanyl through intact skin was evaluated for 24 hours postoperatively in eight patients who had undergone orthopedic surgery. Plasma samples were obtained over a 72-hour period for pharmacokinetic analysis in five patients. The patients were also evaluated intensively for adequacy of analgesia, frequency of nausea and sedation, and occurrence of ventilatory depression.

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We report a model that provides a strong correlation between mouse toxicity data [mouse lethal dose 10% (LD10)] and human plasma concentration-versus-time (CXT) data for 22 commonly used anticancer agents. Mouse toxicity data (LD10) from two dosing schedules, daily times one and daily times seven, were evaluated for the two mouse strains BDF/1 and Swiss. Data from BDF/1 mice were selected for analysis because they were more abundant.

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The influence of enteral feedings (with Ensure) on the absorption of phenytoin sodium from capsules was studied. Six healthy adult volunteers were given a single dose of phenytoin capsules 400 mg po on two occasions. Blood specimens were collected for 48 hours after each dose.

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