The mfluence of methyl-, hydroxy and ammo substituents on the electrochen-ucal behavlour of simple l,Cnaphthoand l,Cbenzoqumones, model compounds of many qumoid antitumour agents, m aqueous media was studied Sigmficant changes m electrochenncal behaviour were observed, potentially the result of a change m the electron density of the qumone moiety, pre-or post-protonation of substituents, hydrogen bond formation, tautomenzation reactions and stenc mteractions between the qumone moiety and substituents. The mformation obtained was of benefit m the elucidation of the reduction mechanisms of qumoid antitumour agents such as avndmylqumones and mitomycins Many well-known anticancer agents, such as the anthracyclines (doxorubicin), the rmtomycins (mitomycm C) and the aziridmylqumones (carboquone and trenimon), have a quinone function, whereas mitoxantrone, AZQ and BZQ are more recently developed quinoid agents, currently m phase I and II clinical trials (Fig. 1).

VP 16-213 in standard doses is active against a number of solid tumors. Its penetration into the cerebrospinal fluid (CSF) is very limited at these dose levels. In 10 patients treated with high-dose VP 16-213 (0.9-2.5 g/m2), CSF levels of up to 0.54 microgram/mL were detected. In two patients with central nervous system (CNS) metastases of small cell lung cancer (SCLC) a response was seen after 1.0 and 1.5 g/m2 intravenously. High-dose VP 16-213 can possibly play a role in the treatment of CNS metastases of SCLC. Its application in late intensification regimens as a form of prophylaxis of CNS metastases should be investigated.

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