As a result, single-agent, sequential chemotherapy remains the standard of care for many patients. Caution should be used in assuming that all schedules of Abraxane are comparable in terms of activity. In addition, there is some evidence to suggest that tesetaxel may have utility in cancers that have developed resistance to the conventional taxanes.
There were no hypersensitivity reactions. One of the major common toxicities of taxanes is neurotoxicity peripheral sensory neuropathy which is dose limiting and cumulative.
The drug stabilises microtubules, inducing potent cytotoxicity in a wide range of tumour cell types. Antitumor activity by individual patient is shown in the following figure. Interestingly, preclinical studies have shown the cytotoxic activity of tesetaxel to be ten- and three-times greater than paclitaxel and docetaxel, respectively.
Patient best response confirmed is shown in the following figure.
Another serious side effect associated with taxanes includes neuropathy, which limits the maximum amount of these drugs that can be given to patients. Two patients died of neutropenia-related complications. However, currently-approved taxanes require intravenous infusion under close medical supervision due to a high level of toxicity.
These agents have broad-spectrum activity in solid tumor malignancies, and are currently in daily use for the treatment of advanced and early stage malignances. Footnotes The authors report no conflicts of interest in this work. Tesetaxel appears to be associated with a lower incidence of peripheral nerve damage. The premise for this was the hypothesis that certain natural fatty acids are taken up avidly by tumors for use as biochemical precursors and energy sources.
The isolation and structure of taxol, a novel antileukemic and antitumor agent from Taxus brevifolia. The binding was concentration independent, indicating a nonspecific, nonsaturable process. Response by Level of P-gp Expression Tesetaxel was generally well tolerated.
Tesetaxel was generally well tolerated. Patients were stratified by prior adjuvant taxane use and hormone receptor status. Response unconfirmed by level of P-gp expression for these patients is shown in the following figure.
Tesetaxel - Orally Administered Taxane Therapy
Tesetaxel is administered orally, which obviates the risk of taxane-related infusion reactions and the need for associated premedications, thus potentially improving safety. As other taxanes, it is a tubulin-targeting drug that causes a defect in the mitotic spindle assembly. By contrast, tesetaxel monotherapy or tesetaxel plus capecitabine are all-oral regimens that do not require administration in an infusion center. Responses were seen in untreated advanced cholangiocarcinoma, and carcinoma of the gastroesophageal junction.
The goal of development of novel taxanes has been focused on the discovery of less neurotoxic derivatives with improved antitumor activity. Tesetaxel is a novel oral semi-synthetic taxane. All patients received an anthracycline-based regimen in the adjuvant or metastatic setting.