Treatment of malignant meningeal disease with intrathecal thioTEPA: a phase II study
In an effort to add to the limited number of effective intrathecal chemotherapeutic agents for malignant meningeal disease we have evaluated the alkylating agent thioTEPA. In phase I testing thioTEPA proved safe at doses as high as 10 mg/m2 and, in addition, showed indications of efficacy at doses as low as 2 mg/m2. The results of phase II testing of this agent are presented in this paper. Thirteen patients received 83 doses of thioTEPA in 16 courses of treatment. Ten patients had meningeal leukemia, six from acute myeloblastic leukemia (AML), three from acute lymphoblastic leukemia (ALL), and one from blast crisis of chronic myelocytic leukemia. The three other patients had meningeal metastatic carcinomatosis, two from metastatic lung carcinomas and the other from metastatic melanoma. Two of the 13 patients are considered nonevaluable because of concomitant whole-head irradiation and a third because she failed to survive until a second CSF specimen could be obtained. The therapeutic efficacy of intrathecal thioTEPA seen in this study clearly establishes that this agent may be a useful addition to the limited intrathecal drug armamentarium. Further clinical trials will provide more information on the ability of intrathecal thioTEPA to induce and maintain meningeal remissions and will define this agent's optimal dose and related toxicity.