Related Experiment Videos
[Phase I and pharmacokinetic study of KRN8602, a new morpholino anthracycline]
M Tabata1, M Ogawa, N Horikoshi
1Dept. of Clinical Oncology, Japanese Foundation for Cancer Research, Tokyo.
Abstract:
Phase I clinical trial of a new semi-synthetic morpholino anthracycline derivative, KRN8602, was performed. Sixteen patients with advanced malignant neoplasms refractory to standard chemotherapies received 27 courses at doses ranging from 1.5 mg/m2/day to 18 mg/m2/day by bolus injection for three consecutive days. The dose limiting toxicity was leukopenia, and a maximally tolerated dose was 18 mg/m2/day (day 1-3). The recommended dose and schedule for a phase II study is determined to be 12 mg/m2/day for three consecutive days at 3-4 weeks intervals. Among non-hematologic toxicities, nausea and vomiting were severe, but stomatitis and alopecia were rarely observed. Clinical signs of cardiotoxicity were not seen.
Insights
A Phase I trial of KRN8602, a novel morpholino anthracycline derivative, found leukopenia as the dose-limiting toxicity. The recommended dose for Phase II studies is 12 mg/m2/day for three days.
Area of Science:
- Oncology
- Pharmacology
- Clinical Pharmacology
Context:
- Advanced malignant neoplasms often exhibit resistance to conventional chemotherapies.
- Novel therapeutic agents are crucial for overcoming treatment resistance in cancer patients.
- Morpholino anthracycline derivatives represent a promising class of anticancer compounds.
Purpose:
- To evaluate the safety and tolerability of KRN8602 in patients with advanced cancers.
- To determine the dose-limiting toxicity and maximally tolerated dose of KRN8602.
- To establish a recommended dose and schedule for future Phase II clinical trials.
Summary:
- A Phase I trial administered KRN8602 to 16 patients with refractory advanced cancers.
- Doses ranged from 1.5 to 18 mg/m2/day for three consecutive days.
- Leukopenia was the dose-limiting toxicity, with a maximally tolerated dose of 18 mg/m2/day.
- The recommended dose for Phase II studies is 12 mg/m2/day (days 1-3) every 3-4 weeks.
- Non-hematologic toxicities included severe nausea and vomiting; stomatitis and alopecia were rare.
- No clinical signs of cardiotoxicity were observed.
Impact:
- Establishes a safe and tolerable dose for KRN8602 in Phase II trials.
- Provides crucial data for the development of a new semi-synthetic anthracycline derivative.
- Offers a potential new treatment option for patients with refractory advanced cancers.
- Highlights the manageable toxicity profile of KRN8602, with a notable absence of cardiotoxicity.