Phase I evaluation of AT-125 single dose every three weeks.

Area of Science:

• Pharmacology
• Clinical Oncology
• Neuroscience

Background:

• AT-125 is an investigational agent evaluated in Phase I clinical trials.
• Understanding the safety profile and dose-limiting toxicities of novel agents is crucial for further development.
• Central nervous system (CNS) toxicity is a potential concern with various chemotherapeutic agents.

Purpose of the Study:

• To evaluate the safety and tolerability of AT-125 administered on a bolus dose every three weeks schedule.
• To identify the dose-limiting toxicities (DLTs) associated with this AT-125 regimen.
• To determine the maximum tolerated dose (MTD) for future clinical studies.

Main Methods:

• A Phase I clinical trial was conducted.
• Patients received AT-125 via bolus dose every three weeks.
• Dose escalation was performed, and toxicity assessments, including neurological examinations, were conducted.
• Dose-limiting toxicities were defined and recorded.

Main Results:

• The primary dose-limiting toxicity was central nervous system (CNS) effects, manifesting as ataxia, confusion, hallucinations, and dysarthria.
• These CNS symptoms were observed at all dose levels, with greatest severity at 150 mg/m2.
• Moderate to severe nausea and vomiting were reported at higher doses.
• No significant myelosuppression was observed during the trial.

Conclusions:

• The bolus every three weeks schedule of AT-125 is associated with significant CNS toxicity.
• This schedule is not recommended for Phase II studies in its current form.
• Further research is needed to develop strategies for mitigating AT-125-related CNS toxicity before proceeding to later-phase trials.