Topotecan-based combination chemotherapy for human malignant glioma.
BACKGROUND
Topotecan has been considered a promising agent for the adjuvant chemotherapy of human malignant glioma because of its novel mode of action, its activity against other solid tumors, and its good penetration across the blood-brain barrier. However, the clinical effects of topotecan monotherapy in malignant glioma have been disappointing.


METHODS
We sought to identify suitable partners for topotecan combination chemotherapy of malignant glioma using two well-characterized human malignant glioma cell lines, T98G and LN-229. The effects of co-exposure to topotecan and other chemotherapy drugs were assessed in cytotoxic and clonogenic cell death assays.


RESULTS
We found additive, less-than-additive, or occasional antagonistic effects, but never synergistic activity of topotecan with either CCNU, VM26 or vincristine, in acute cytotoxicity or in clonogenic cell death assays, with simultaneous or sequential drug exposure. VM26 or vincristine followed by topotecan yielded the most favourable results. Further, prolonged exposure of the glioma cells to topotecan and either CCNU, VM26, vincristine, cisplatin, doxorubicin or cytarabine resulted in additive but not synergistic growth inhibition.


CONCLUSIONS
The present study fails to identify a specific partner for topotecan-based combination chemotherapy of malignant glioma among the chemotherapeutic drugs examined here. While this does not exclude a possible synergy of the drug combinations examined here in vivo, a focus on novel partners for topotecan or topotecan-based chemoimmunotherapy may be more promising.
Schmidt
F
F
Department of Neurology, University of Tübingen, Germany.
Schuster
M
M
Streffer
J
J
Schabet
M
M
Weller
M
M
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D005910:Glioma / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D008130:Lomustine / Q000008:administration & dosage; D013713:Teniposide / Q000008:administration & dosage; D019772:Topotecan / Q000008:administration & dosage*; D014407:Tumor Cells, Cultured; D014410:Tumor Stem Cell Assay; D014750:Vincristine / Q000008:administration & dosage
D014750:Vincristine; D008130:Lomustine; D019772:Topotecan; D013713:Teniposide