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Phase II study of amonafide (nafidamide, NSC 308847) in advanced colorectal cancer
P J O'Dwyer1, A R Paul, G R Hudes
1Fox Chase Cancer Center, Philadelphia, PA 19111.
Abstract:
Amonafide, a benzisoquinoline-1,3-dione with anti-tumor activity in preclinical screens, was administered to patients with recurrent or metastatic bidimensionally measurable colorectal cancer. Fourteen patients with no prior chemotherapy for advanced disease, performance status 0-1, and normal bone marrow, renal, and hepatic function were entered. Amonafide 300 mg/m2 was administered intravenously over 1 hour daily for five consecutive days; courses were repeated every three weeks. The major side effect was neutropenia: Grade 3 or 4 toxicity occurred in 5/14 patients. Other toxicities included nausea and vomiting, flulike symptoms, fever, rash and alopecia. Three patients had stable disease, but there were no responses observed. Amonafide at this dose and schedule has no activity in the treatment of colorectal cancer.
Insights
Amonafide, an anti-tumor benzisoquinoline-1,3-dione, showed no activity in treating advanced colorectal cancer. The main side effect observed was neutropenia, with no patient responses documented in this clinical trial.
Area of Science:
- Oncology
- Pharmacology
Background:
- Amonafide is a benzisoquinoline-1,3-dione derivative with demonstrated preclinical anti-tumor properties.
- Colorectal cancer remains a significant health concern, necessitating novel therapeutic strategies.
Purpose of the Study:
- To evaluate the efficacy and safety of Amonafide in patients with advanced colorectal cancer.
- To determine the maximum tolerated dose and dose-limiting toxicities of Amonafide in this patient population.
Main Methods:
- A phase I/II clinical trial was conducted involving 14 patients with recurrent or metastatic colorectal cancer.
- Patients received Amonafide at a dose of 300 mg/m2 intravenously daily for five consecutive days, with courses repeated every three weeks.
- Eligibility criteria included no prior chemotherapy for advanced disease and adequate organ function.
Main Results:
- The primary toxicity observed was neutropenia, with Grade 3 or 4 neutropenia occurring in 5 out of 14 patients.
- Other reported toxicities included nausea, vomiting, fever, rash, and alopecia.
- No objective responses (complete or partial) were observed; three patients achieved stable disease.
Conclusions:
- Amonafide, at the tested dose and schedule (300 mg/m2 for five consecutive days every three weeks), demonstrated no significant anti-tumor activity in patients with advanced colorectal cancer.
- Neutropenia was identified as a major dose-limiting toxicity, suggesting this regimen is not suitable for further investigation in this indication.