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In vitro activity of amonafide against primary human tumors compared with the activity of standard agents
J A Ajani1, F L Baker, G Spitzer
1Department of Medical Oncology, University of Texas M.D. Anderson Hospital and Tumor Institute, Houston 77030.
Abstract:
Amonafide, one of a series of benz[de]-isoquinoline-1,3-dione compounds, is now entering phase II clinical trials in this country. We tested amonafide, exposed continuously for 5 days, at four different concentrations against 56 primary human tumors in vitro. The drug concentration range used was based on amonafide's inhibitory activity against human bone marrow cells. The antitumor activity of 5-fluorouracil, mitomycin C, cisplatin, and etoposide against tumors from this panel of 56 was compared with that of amonafide at in vitro concentrations equitoxic against human bone marrow cells. Amonafide was active against only 12% of tumors compared with standard agents, which were active against more than 40% of tumors in the human bone marrow inhibitory range. Our data suggested that amonafide is less likely to be clinically active against human solid tumors than the standard agents.
Insights
Amonafide showed limited activity against most human tumors in vitro. Standard chemotherapy agents demonstrated superior efficacy in preclinical models, suggesting amonafide may be less effective against solid tumors.
Area of Science:
- Oncology
- Pharmacology
- Cancer Research
Background:
- Amonafide, a benz[de]-isoquinoline-1,3-dione derivative, is advancing to Phase II clinical trials.
- Preclinical evaluation is crucial for assessing potential clinical efficacy.
Purpose of the Study:
- To evaluate the in vitro antitumor activity of amonafide against a panel of 56 primary human tumors.
- To compare amonafide's efficacy with standard chemotherapeutic agents (5-fluorouracil, mitomycin C, cisplatin, etoposide) at equitoxic concentrations against human bone marrow cells.
Main Methods:
- Continuous in vitro exposure of 56 primary human tumors to amonafide for 5 days.
- Drug concentrations were determined based on amonafide's inhibitory effects on human bone marrow cells.
- Comparative analysis of amonafide and standard agents against tumor cells and bone marrow cells.
Main Results:
- Amonafide demonstrated activity against only 12% of the tested human tumors.
- Standard agents exhibited activity against over 40% of tumors at comparable bone marrow inhibitory concentrations.
- A significant difference in antitumor activity was observed between amonafide and the standard agents.
Conclusions:
- Amonafide exhibits limited in vitro antitumor activity against a broad range of human solid tumors.
- Standard chemotherapeutic agents show greater preclinical efficacy compared to amonafide.
- These findings suggest a lower likelihood of clinical success for amonafide in treating human solid tumors compared to established therapies.