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The epipodophyllotoxin derivatives VM-26 and VP-16-213, 1976-1979, a review
Abstract:
The epipodophyllotoxin derivatives VM 26 and VP 16-213 are currently entering phase III studies. The mechanism of their action is incompletely understood, but the greatest lethal effect is experienced in the late S and G2 phases. In transplanted tumors both drugs have shown marked schedule dependency and human studies also support this. As a single agent VP 16-213 is among the most active drugs in small-cell carcinoma of the lung. Significant clinical activity (> 20% response frequency) has been observed for both drugs in Hodgkin's disease, non-Hodgkin lymphomas and possibly in other more rare tumors (monocytic leukemia, hepatoma and teratoma). Although further clinical studies of both drugs would be ideal, it seems possible at present to justify a discontinuation of VM-26 in order to concentrate the efforts on VP 16-213. Further studies are needed to define optimal dose and schedule and place in combination chemotherapy.
Insights
Epipodophyllotoxin derivatives VM 26 and VP 16-213 show significant activity in various cancers. VP 16-213 is particularly effective in small-cell lung cancer, suggesting a focus on this agent is warranted.
Area of Science:
- Oncology
- Pharmacology
- Cancer Chemotherapy
Background:
- Epipodophyllotoxin derivatives VM 26 and VP 16-213 are investigational agents.
- Their precise mechanism of action and optimal therapeutic use require further elucidation.
Purpose of the Study:
- To review the clinical activity and schedule dependency of VM 26 and VP 16-213.
- To evaluate the potential for focusing clinical development efforts on VP 16-213.
Main Methods:
- Review of preclinical and clinical data on VM 26 and VP 16-213.
- Analysis of drug efficacy in various tumor types, including transplanted tumors and human malignancies.
Main Results:
- Both VM 26 and VP 16-213 exhibit marked schedule dependency in transplanted tumors.
- VP 16-213 demonstrates high single-agent activity in small-cell lung carcinoma.
- Significant clinical responses (>20%) observed for both drugs in Hodgkin's disease, non-Hodgkin lymphomas, and rare tumors.
Conclusions:
- Clinical development may benefit from concentrating on VP 16-213.
- Further research is necessary to determine optimal dosing, scheduling, and combination chemotherapy regimens.