Phase I study of aziridinylbenzoquinone (NSC 182986)

Area of Science:

• Oncology
• Clinical Pharmacology

Background:

• Advanced solid tumors present significant treatment challenges.
• Novel chemotherapeutic agents are crucial for improving patient outcomes.

Purpose of the Study:

• To evaluate the toxicity and efficacy of aziridinylbenzoquinone (AZQ) in a phase I clinical study.
• To determine the recommended starting dose for phase II trials.

Main Methods:

• Phase I clinical trial involving 33 patients with advanced solid tumors.
• Dose escalation of aziridinylbenzoquinone (AZQ) from 0.5 mg/m2/day to 12.0 mg/m2/day.
• Monitoring for toxicity, particularly thrombocytopenia, anemia, nausea, and vomiting.

Main Results:

• Thrombocytopenia was the dose-limiting toxicity, characterized as delayed and cumulative.
• Anemia was frequent and severe at higher doses; nausea and vomiting were generally mild.
• Objective tumor regressions occurred in 3 of 17 patients receiving biologically active AZQ doses (≥6 mg/m2/day).

Conclusions:

• Aziridinylbenzoquinone (AZQ) demonstrates anti-tumor activity in advanced solid tumors.
• The recommended starting dose for phase II studies is 8.0 mg/m2/day for good-risk patients.
• Careful monitoring for thrombocytopenia is essential during AZQ treatment.