PENETRATION OF VP 16-213 INTO CEREBROSPINAL-FLUID AFTER HIGH-DOSE INTRAVENOUS ADMINISTRATION

VP 16-213 in standard doses is active against a num-ber of solid tumors. Its penetration into the cerebrospi-nal fluid (CSF) is very limited at these dose levels. In 10 patients treated with high-dose VP 16-213 (0.9-2.5 g/m 2), CSF levels of up to 0.54 tg/mL were detect-ed. In two patients with central nervous system (CNS) VP 16-213 is a semisynthetic podophyllo-toxin derivative that is active against a number of solid tumors. 1.2 Major therapeutic ac-tivity for the drug has been found in small cell lung cancer (SCLC) and germ-cell malignan-cies. 3 " Dosages up to 400 mg/m 2 showed minor, primarily hematologic toxicity.,2 Pharmacoki-netic studies at these conventional dose levels in humans showed hardly any penetration of VP 16-213 into the cerebrospinal fluid (CSF).7 Increas-ing the dosage of VP 16-213 up to 1,500 mg/m2 leads to severe reversible myelosuppression in humans but only minor extramedullary toxicity.8 In two phase I studies on the feasibility of high-dose VP 16-213 in patients with progres-sive solid tumors, we investigated CSF levels and the effect against central nervous system (CNS) metastases from SCLC