Related Experiment Videos
Phase II trial of piroxantrone for advanced or metastatic soft tissue sarcomas. A Southwest Oncology Group study
M M Zalupski1, J Benedetti, S P Balcerzak
1Wayne State University Medical Center, Detroit, MI.
Abstract:
Piroxantrone is an anthrapyrazole compound undergoing phase II testing in a variety of diseases. The anthrapyrazoles are a series of compounds synthesized with the intent of maintaining the broad antitumor activity of anthracyclines, but with lessened cardiac toxicity. The Southwest Oncology Group (SWOG) conducted a phase II trial of piroxantrone in advanced soft tissue sarcoma. Treatment consisted of piroxantrone 150 mg/M2 administered intravenously over 1 hour every 21 days. Twenty-five eligible patients were registered to the trial. Twenty-three patients received treatment and are fully evaluable for response and toxicity. Two partial responses were seen for an overall response rate of 9% (95% confidence limit 1%-28%). Abnormal cardiac ejection fraction occurred in five patients, and fatal congestive heart failure developed in one patient on study. Toxicities other than cardiac were tolerable. Based on the observed response rate and cardiac toxicity, further trials of piroxantrone in the treatment of soft tissue sarcoma do not appear warranted.
Insights
Piroxantrone showed a 9% response rate in advanced soft tissue sarcoma. Due to cardiac toxicity, including one fatal case, further trials of this anthrapyrazole compound are not recommended.
Area of Science:
- Oncology
- Pharmacology
Background:
- Anthrapyrazole compounds, like piroxantrone, were developed to retain the antitumor efficacy of anthracyclines while reducing cardiotoxicity.
- Piroxantrone is an investigational drug evaluated for various oncological indications.
Purpose of the Study:
- To assess the efficacy and safety of piroxantrone in patients with advanced soft tissue sarcoma.
Main Methods:
- A Phase II trial was conducted by the Southwest Oncology Group (SWOG).
- Twenty-three eligible patients received intravenous piroxantrone at 150 mg/M2 every 21 days.
- Response and toxicity were evaluated.
Main Results:
- An overall response rate of 9% (95% confidence interval 1%-28%) was observed, with two partial responses.
- Cardiac toxicity included abnormal ejection fraction in five patients and one fatal case of congestive heart failure.
- Non-cardiac toxicities were generally tolerable.
Conclusions:
- Piroxantrone demonstrated limited efficacy in advanced soft tissue sarcoma.
- The observed cardiac toxicity profile suggests that further investigation of piroxantrone for this indication is not warranted.