[Phase I study of NK 622 (toremifene citrate)]

Area of Science:

• Pharmacology
• Oncology
• Clinical Trials

Background:

• NK 622 (toremifene citrate) is a novel antiestrogen investigated for potential therapeutic applications.
• Estrogen receptor modulation is a key strategy in treating hormone-sensitive cancers.

Purpose of the Study:

• To evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of NK 622 in a phase I study.
• To determine a safe and effective dose range for future clinical trials in cancer patients.

Main Methods:

• Phase I clinical trial involving single and multiple oral doses of NK 622 in female cancer patients.
• Adverse events, serum hormone levels (including sex hormone binding globulin), and serum concentrations of NK 622 and its metabolite (N-demethyltoremifene) were monitored.

Main Results:

• Single doses of 40-60 mg were well-tolerated. Daily dosing up to 240 mg/day showed manageable adverse events like anorexia, leukopenia, hot flushes, nausea, fatigue, and headache, which resolved post-treatment.
• Significant increases in sex hormone binding globulin were observed at 120 and 240 mg/day.
• Pharmacokinetic analysis revealed dose-dependent increases in serum levels of NK 622 (TOR) and its metabolite (TOR-1), with long half-lives.

Conclusions:

• NK 622 is generally safe and well-tolerated at doses up to 240 mg/day.
• Doses of 240 mg or less are recommended for further investigation in phase II studies for long-term treatment, particularly in breast cancer patients.