Background: We investigated the efficacy and safety of 60, 120, or 240 mg of Z-360, which is a highly potent cholecystokinin2-receptor-selective antagonist, combined with gemcitabine in patients with metastatic pancreatic cancer.
Methods: Patients were randomly assigned in a 1:1:1:1 ratio to one of four treatment groups. Patients received 1000 mg/m gemcitabine for each cycle and Z-360 tablets of 60 mg (GZ 60 mg group), 120, 240 mg or placebo tablets (Gem group) orally twice daily. The primary endpoint was overall survival (OS).
Results: The median OS was 1.3 months longer in the GZ 60 mg group compared with the Gem group (8.5 vs. 7.2 months) and the risk of death was reduced by 19% compared with the Gem group, although there were no statistically significant differences. The study treatments were well tolerated.
Conclusions: In this Phase II study, no statistically significant differences between the GZ groups and Gem group were detected in any analysis. However, Z-360 in dose of 60 mg tends to improve OS in patients with metastatic pancreatic cancer with low toxic effect. Further exploratory trials with other agents such as gemcitabine plus nab-paclitaxel might be beneficial.
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http://dx.doi.org/10.1007/s00280-017-3351-4 | DOI Listing |
BMC Pulm Med
January 2025
Department of Respiratory Medicine, Faculty of Life Sciences, Kumamoto University, Kumamoto 1-1-1 Honjo, Chuo-ku, 860-8556, Japan.
Background: Fibrotic types of interstitial lung abnormalities seen on high-resolution computed tomography scans, characterised by traction bronchiolectasis/bronchiectasis with or without honeycombing, are predictors of progression and poor prognostic factors of interstitial lung abnormalities. There are no reports on the clinical characteristics of fibrotic interstitial lung abnormalities on high-resolution computed tomography scans. Therefore, we aimed to examine these clinical characteristics and clarify the predictive factors of fibrotic interstitial lung abnormalities on high-resolution computed tomography scans.
View Article and Find Full Text PDFJ Am Chem Soc
January 2025
Department of Chemistry, Colorado State University, Fort Collins, Colorado 80523-1872, United States.
Enthalpy is often the focal point when designing monomers for polymer circularity, but much less is explored on how entropy can be exploited to create polymers with synergistic circularity and properties. Here, we design a series of spiro-lactones (SLs) with closed-chain cycloalk(en)yl substituents at the α,α-position of δ-valerolactone (δVL), which, when combined with the parent δVL and -α,α-dialkyl-substituted δVL with open-chain alkyl groups, provide a desired platform for exploring the circular polymer design by focusing on the entropy change of polymerization. These SLs exhibit finely balanced (de)polymerizability that is regulated chiefly by entropy differentiation, allowing both the facile synthesis of polyester PSLs ( up to 1000 kg mol) in a living fashion and selective depolymerization of the PSLs to completely recover monomers under mild conditions (using a recyclable catalyst at 100 °C).
View Article and Find Full Text PDFMolecules
January 2025
MBC Pharma Inc., Aurora, CO 80045, USA.
Background: The use of the bone-seeking properties of bisphosphonates (BPs) to target the delivery of therapeutic drugs is a promising approach for the treatment of bone metastases. Currently, the most advanced example of this approach is a gemcitabine-ibandronate conjugate (GEM-IB), where the bone-targeting BP ibandronate (IB) is covalently linked to the antineoplastic agent gemcitabine (GEM) via a spacer phosphate group. In the present study, we describe the development of a new analytical platform to evaluate the metabolism and pharmacokinetics of GEM-IB in mice and dogs and the results of proof-of-concept studies assessing the pharmacokinetics of GEM-IB in dogs and mice.
View Article and Find Full Text PDFJ Pers Med
January 2025
Department of Obstetrics and Gynecology, "Victor Babeș" University of Medicine and Pharmacy, 300041 Timișoara, Romania.
: Platinum-resistant ovarian cancer (PROC) is a major therapeutic challenge, as it responds poorly to standard platinum-based treatment, has limited treatment options, and offers a generally unfavorable prognosis. Chemotherapeutic agents like pegylated liposomal doxorubicin (PLD), topotecan (TOPO), and gemcitabine (GEM) are used for this setting, but with varying efficacy and toxicity profiles, leading to an increasing need to understand the optimal balance between treatment effectiveness and tolerability for improving patient outcomes. This study evaluates the efficacy and side effects of PLD, TOPO, and GEM, focusing on progression-free survival (PFS), overall survival (OS), and safety profiles.
View Article and Find Full Text PDFChem Sci
January 2025
Aix Marseille University, Université de Toulon, CNRS, IM2NP 13013 Marseille France
We investigated the reactivity of a -dichlorovinyl-carbazole precursor in the on-surface synthesis approach. Our findings reveal that, on the Au(111) surface, the thermally-induced dehalogenation reaction led to the formation of cumulene dimers. Contrastingly, the more reactive Cu(111) surface promoted the formation of a polyheterocyclic compound exhibiting extended aromaticity.
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