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Pharmacology of N-(3,5-dichloro-1-oxido-4-pyridinyl)-8-methoxy-2-(trifluoromethyl)-5-quinoline carboxamide (SCH 351591), a novel, orally active phosphodiesterase 4 inhibitor.

N-(3,5-Dichloro-1-oxido-4-pyridinyl)-8-methoxy-2-(trifluoromethyl)-5-quinoline carboxamide (SCH 351591) has been identified as a potent (IC(50) = 58 nM) and highly selective type 4 phosphodiesterase (PDE4) inhibitor with oral bioactivity in several animal models of lung inflammation. N-(3,5-Dichloro-4-pyridinyl)-8-methoxy-2-(trifluoromethyl)-5-quinoline carboxamide (SCH 365351), the only significant in vivo metabolite, is also a potent and highly selective PDE4 inhibitor (IC(50) = 20 nM). Both SCH 351591 and SCH 365351 inhibited cytokine production in human blood mononuclear cell preparations.

Cohort study of consistency between the compliance with guidelines for chemotherapy-induced nausea and vomiting and patient outcome.

BackgroundChemotherapy-induced nausea and vomiting is one of the most influential factors that affect patient quality of life; thus, preventing this adverse event could lead to better patient outcome. Standard preventive guidelines for antiemetic treatment have already been established based on the emetogenicity of chemotherapeutic agents. It is important that compliance with in-house guidelines and their effect on patient outcome is monitored.MethodsIn 3 years since the Akita university hospital antiemetic guidelines were outlined, we assessed the incidence of chemotherapy-induced nausea and

Contributions to the phytotherapies of digestive disorders: Traditional knowledge and cultural drivers of Manoor Valley, Northern Pakistan.

ETHNO PHARMACOLOGICAL RELEVANCE: Ethno medicinal traditional knowledge regarding the uses of indigenous medicinal plants used for various human digestive disorders are mostly known to the elder community members. As the young generation is not much aware about such vital traditional medicinal practice because they rely on elders. AIM OF STUDY: To document, accumulate and widely disseminate the massive indigenous knowledge of century's practiced therapeutic uses of medicinal plants by the local people living in this remote area. MATERIALS AND METHODS: A total of 63 local inhabitants (39 males

Editorial: Cancer therapy: The challenge of handling a double-edged sword.

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Antiemetic Strategies in Patients Who Undergo Hematopoietic Stem Cell Transplantation.

Hematopoietic stem cell transplantation (HSCT) is an integral part of the treatment strategy in patients with a hematological disorder. Chemotherapy-induced nausea and vomiting (CINV) is still an issue in patients who undergo HSCT. While several guidelines for the antiemetic therapy against CINV have been published, there is no detailed information about appropriate antiemetic drugs for each conditioning regimen in HSCT. Various studies reported that the triplet of 5-HT3RA, NK1RA, and dexamethasone appears useful in HSCT. However, each antiemetic has unique adverse effects or interactions with

Exploring antiemetic strategies in hematologic malignancies: a comprehensive literature review and evaluation of antiemetic efficacy in patients receiving high-dose chemotherapy prior to hematopoietic stem cell transplantation.

PURPOSE: Most antiemetic studies have been conducted in patients with solid tumors receiving single-dose chemotherapy. A research gap leaves … haracteristics pertaining to randomization, control groups, size, cancer types, chemotherapies, antiemetics, and assessments, making cross-study comparisons and conclusions difficult. The range of response rates was wide with numerous studies showing complete response, no emesis or no nausea rates of less than 50%. Response rates were highest when an NK1 …

Intravenous lidocaine for gastrointestinal recovery after colorectal surgery: the ALLEGRO placebo-controlled randomised trial and cost-effectiveness analysis.

BACKGROUND: Delayed return of gut function after colonic resection is a common impediment to early postoperative recovery. Small clinical studies, combined into meta-analyses, have suggested that intravenous lidocaine can improve return of gut function after colorectal surgery. OBJECTIVE(S): To determine the clinical effectiveness and cost-effectiveness of perioperative intravenous lidocaine infusion compared with placebo in return of gut function after elective minimally invasive colonic resection. DESIGN AND METHODS: Multicentre, pragmatic, placebo-controlled, randomised trial with cost-ef

Fifty years of paracetamol (acetaminophen) poisoning: the development of risk assessment and treatment 1973-2023 with particular focus on contributions published from Edinburgh and Denver.

INTRODUCTION: Fifty years ago, basic scientific studies and the availability of assay methods made the assessment of risk in paracetamol (acetaminophen) poisoning possible. The use of the antidote acetylcysteine linked to new methods of risk assessment transformed the treatment of this poisoning. This review will describe the way in which risk assessment and treatments have developed over the last 50 years and highlight the remaining areas of uncertainty. METHODS: A search of PubMed and its subsidiary databases revealed 1,166 references published in the period 1963-2023 using the combined ter

Efficacy and Safety of Thalidomide for Chemotherapy-induced Nausea and Vomiting.

Purpose: A substantial number of cancer patients discontinue chemotherapy due to severe chemotherapy-induced nausea and vomiting (CINV). This study aimed to evaluate the efficacy and safety of thalidomide (THD) in CINV. Methods: We searched different databases to identify related studies that investigated the efficacy and safety of THD in CINV. The primary outcomes were CINV in the acute (0-24 h), delayed (24-120 h), and overall (0-120 h) phases, respectively. The secondary outcomes were the safety of THD and the patients' quality of life (QOL). Results: Fourteen randomized control trials (RCT

Resminostat for maintenance treatment in patients with advanced-stage mycosis fungoides or Sézary syndrome: a multicentre, double-blind, randomised, placebo-controlled, phase 2 trial.

BACKGROUND: In advanced-stage cutaneous T-cell lymphoma (CTCL), current therapeutic options rarely provide long-lasting responses. We aimed to evaluate the efficacy and safety of a histone deacetylase inhibitor, resminostat, as maintenance therapy in patients with advanced-stage mycosis fungoides or Sézary syndrome, in whom disease control had been previously met. METHODS: We conducted a multicentre, double-blind, randomised, placebo-controlled, phase 2 trial (RESMAIN) at 55 medical centres in Austria, Belgium, France, Germany, Greece, Italy, the Netherlands, Poland, Spain, Switzerland, the U

Mechanisms of Chemotherapy-Induced Neurotoxicity.

Since the first clinical trials conducted after World War II, chemotherapeutic drugs have been extensively used in the clinic as the main cancer treatment either alone or as an adjuvant therapy before and after surgery. Although the use of chemotherapeutic drugs improved the survival of cancer patients, these drugs are notorious for causing many severe side effects that significantly reduce the efficacy of anti-cancer treatment and patients' quality of life. Many widely used chemotherapy drugs including platinum-based agents, taxanes, vinca alkaloids, proteasome inhibitors, and thalidomide ana

Netupitant/palonosetron without dexamethasone for preventing nausea and vomiting in patients with multiple myeloma receiving high-dose melphalan for autologous stem cell transplantation: a single-center experience.

Chemotherapy-induced nausea and vomiting (CINV) is one of the most frequent adverse events compromising quality of life (QoL) in patients undergoing autologous stem cell transplantation (ASCT). However, CINV prophylaxis is still lacking uniformity for high-dose melphalan (HDM), which is used to condition patients with multiple myeloma (MM). Netupitant/palonosetron (NEPA) is administered with dexamethasone (DEXA) for CINV prevention in several chemotherapy regimens. Our study aims to assess the efficacy of NEPA, without DEXA, in preventing CINV in 106 adult patients with MM receiving HDM and AS

Palonosetron in the prevention of chemotherapy-induced nausea and vomiting: an evidence-based review of safety, efficacy, and place in therapy.

IntroductionThe second-generation 5-hydroxytryptamine-3 (5-HT3) receptor antagonist palonosetron is effective in the prevention of chemotherapy-induced nausea and vomiting (CINV) associated with highly and moderately emetogenic chemotherapy (HEC and MEC, respectively). In addition, palonosetron has been the first and, at present, the only 5-HT3 receptor antagonist to have a specific indication for the prevention of delayed CINV associated with MEC. The unique pharmacology of this antagonist is thought to partly explain its improved efficacy against delayed symptoms.AimsTo review the evidence u

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… RCTs were included if they aimed at comparing palonosetron to older antagonists for the prevention of CINV in at least one of the following five end points: CR (defined as no emetic episode and no rescue antiemetics), complete control (CC; defined as no emetic episode, no rescue antiemetics, and no more … Secondary end points included CR in the acute and delayed phases, and total control (TC; defined as no emetic episodes, no rescue antiemetics, and no nausea) during all the study periods. The study had a 90% power to detect a 10% improvement in the overall CR rate. …

Innovations in chemotherapy and radiation therapy: Implications and opportunities for the Asia-Pacific Rim.

New cases of invasive cancer in the United States occur among nearly 1.5 million people annually. In 2007, more than 1,500 people died per day with this diagnosis. Cancer is responsible for nearly one in every four deaths reported in the country. Enormous amounts of money and research have been, and are being spent, in an attempt to improve these numbers. While prevention and early detection remain the key to long-term success, treatment in the neo-adjuvant, adjuvant and metastatic settings still centre around two main treatment modalities - radiation therapy and chemotherapy. This article wil

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… The major advances have come in the areas of anti-emetics, growth factor support and bone health. … Anti-Emetics New classes of anti-emetics, such as the serotonin (5-HT3) receptor antagonists and neuro-kinin 1 (NK-1) antagonists, have played a major role in decreasing the incidence and severity of chemotherapy-induced nausea and vomiting (CINV). See Table 3 . …

Management of adverse events associated with ixazomib plus lenalidomide/dexamethasone in relapsed/refractory multiple myeloma.

The oral proteasome inhibitor ixazomib is approved in the United States, European Union and other countries, in combination with oral lenalidomide and dexamethasone (Rd), for the treatment of patients with multiple myeloma who have received at least one prior therapy. Approval was based on the global, randomised, double-blind, placebo-controlled Phase III TOURMALINE-MM1 study of ixazomib-Rd (IRd) versus placebo-Rd in patients with relapsed/refractory multiple myeloma. IRd resulted in a significant improvement in progression-free survival versus placebo-Rd (median: 20·6 vs. 14·7 months; hazard

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… The most commonly prescribed anti‐emetics were ondansetron and metoclopramide. … Considering the emetogenic potential of ixazomib, adequate anti‐emetic therapy based on patients’ needs and prophylactic anti‐emetics, where appropriate, should be considered (Hesketh et al , 2016 ). …

Olanzapine versus aprepitant for the prophylaxis of chemotherapy-induced nausea and vomiting in breast cancer patients receiving doxorubicin-cyclophosphamide regimen: A prospective, nonrandomized, open-label study.

OBJECTIVE: Despite the guideline-directed therapy, complete absence of nausea was noted only in 33% of breast cancer patients on anthracycline-cyclophosphamide regimen. Hence, we sought to compare the efficacy of aprepitant (APT) versus olanzapine (OLP) in preventing chemotherapy-induced nausea and vomiting (CINV) in breast cancer patients on doxorubicin-cyclophosphamide regimen. PATIENTS AND METHODS: A prospective, open-label, nonrandomized study was conducted at the Department of Oncology. Eighty-three patients completed the study with 43 in the APT group and 40 in OLP group. Data about nau

Recent advances in antiemetics: new formulations of 5HT3-receptor antagonists.

PurposeTo discuss new therapeutic strategies for chemotherapy-induced nausea and vomiting (CINV) involving 5-hydroxytryptamine type 3 (5HT3) … therapy. GERSC, the most recently approved 5HT3-RA formulation, is indicated for use with other antiemetics to prevent acute and delayed nausea and vomiting associated with initial and repeat courses of MEC and anthracycline-cyclophosphamide combination-chemotherapy regimens.

Evolving role of neurokinin 1-receptor antagonists for chemotherapy-induced nausea and vomiting.

To examine pharmacologic and clinical characteristics of neurokinin 1 (NK1)-receptor antagonists (RAs) for preventing chemotherapy-induced n … ability, and increase clinicians' opportunities to maximize benefits of this important class of antiemetics.