We report a novel method for screening and quantifying tubulin-binding antimitotic agents that promote microtubule formation. The method is based on the shift in the peak of the fluorescence emission difference spectrum of tubulin complexed to metal free tetrakis(4-carboxyphenyl)porphyrin (TCPP) in the presence of antimitotic agents. Taxol (paclitaxel), an anti-tumor drug approved for the treatment of a variety of cancers, caused the appearance of a new fluorescence peak at 645 nm at concentrations as low as 125 nM, the intensity of which was a function of the paclitaxel concentration. Cephalomannine caused the induction of a new fluorescence peak at 651 nm only above 1 muM. Baccatin did not induce the appearance of any new peak within detectable operating measurement conditions. These observations are in accordance with the biological activities/cytotoxicities of these compounds. Accordingly, it is proposed that the new method can be used for high throughput screening of antimitotic compounds.
Background Peripheral neuropathy is a common dose-limiting side effect of paclitaxel. To date, there is no effective strategy to prevent paclitaxel-induced peripheral neuropathy. A recent small phase II study demonstrated the potential role of oral gabapentin in this setting. This phase III study is aimed to assess the efficacy of oral gabapentin in preventing paclitaxel-induced neuropathy. Objective To compare the efficacy of oral gabapentin with placebo in preventing clinically significant peripheral neuropathy (NCI CTCAEv5.0 grade 2 or higher) in patients receiving paclitaxel. Methods This is a randomized, placebo-controlled, double-blind, parallel-group superiority trial. The primary outcome is the development of grade 2 or higher chemotherapy-induced peripheral neuropathy. Secondary outcomes include any grade neuropathy, the percentage change in sensory nerve conduction velocities in peripheral nerves, time to development of any grade neuropathy, paclitaxel dose reductions and delays due to peripheral neuropathy, patient-reported outcomes, adverse events, and adherence to oral therapy. A total of 136 patients receiving paclitaxel will be randomly allocated (stratified by weekly vs. non-weekly administration) to receive either oral gabapentin or placebo till three weeks after the last dose of chemotherapy or occurrence of the primary outcome. Conclusion This study aims to find if oral gabapentin reduces the incidence of grade 2 or higher chemotherapy-induced peripheral neuropathy in patients receiving paclitaxel. Trial registration The trial is registered prospectively with the Clinical Trials Registry of India (CTRI/2022/02/040030) on April 4, 2022.
Background Distal symmetrical neuropathy is a common dose – limiting adverse effect of paclitaxel. A multitude of preventive strategies have been tried with futility in phase 3 settings. A recent phase 2 study has shown potential role of oral gabapentin in prevention of paclitaxel induced neuropathy. In this study, we aim to compare oral gabapentin with placebo in the prevention of paclitaxel induced neuropathy. Objective To evaluate the efficacy of oral gabapentin in preventingsensory neuropathy (NCI CTCAEv5.0 grade 2 or higher) in patients receiving paclitaxel. Methods This is a randomized, placebo controlled, double blind, parallel group superiority trial. A total of 136 patients receivingpaclitaxel therapy will be randomly allocated (stratified by weekly vs. non-weekly administration) to receive either oral gabapentin or placebo for the duration of paclitaxel therapy, till completion of therapy or occurrence of the primary outcome. The patients will be followed up until three months after end of therapy. The primary outcome is the proportion of patients who develop grade 2 or higher chemotherapy induced sensory neuropathy. Secondary outcomes include any grade neuropathy, percentage change in sensorynerve conduction velocities in median, ulnar, and sural nerves, time to develop neuropathy, paclitaxel dose reductions and delays due to sensory neuropathy, patient-reported outcomes, adverse events, and adherence to oral therapy. Conclusion This study aims to find if oral gabapentin reduces incidence of grade 2 or higher chemotherapy induced sensory neuropathy in patients receiving paclitaxel. Trial registration The trial is registered prospectively with the Clinical Trials Registry of India (CTRI/2022/02/040030) on April 4, 2022.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.