First human treatment of resistant neoplastic meningitis by intrathecal administration of MTX Plus 125IUdR

Author： Rebischung C. Hoffmann D. Stefani L. Desruet M. D. Wang K. Adelstein S. J. Artignan X. Vincent F. Gauchez A. S. Zhang H. Fagret D. Vuillez J. Kassis A. I. Balosso J.

Publisher： Informa Healthcare

ISSN： 1362-3095

Source： International Journal of Radiation Biology, Vol.84, Iss.12, 2008-01, pp. : 1123-1129

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Abstract

Purpose: Neoplastic meningitis is often the final outcome of disseminated cancer and is rapidly lethal. Its limited treatment relies on systemic or intrathecal chemotherapy with methotrexate (MTX) or thiotepa. When 5-iodo-2'-deoxyuridine labeled with 125I (125IUdR) is incorporated into the DNA of mitotic tumor cells, the Auger electrons emitted during iodine decay are highly cytotoxic. The radiotherapeutic efficacy of 125IUdR administered intrathecally has also been established in animals bearing spinal cord tumors, and MTX is known to potentiate the response. This approach has not been tested in the clinic. Methods: A 44-year-old woman, with locally advanced pancreatic cancer, was treated for three years with complete systemic remission, but then relapsed with cytologically proven neoplastic meningitis. The patient was given four successive intrathecal injections of MTX (10 mg) every 12 h and, with the fourth dose, 1850 MBq 125IUdR, followed by four additional MTX doses. The response was monitored by cytology and CA19.9 (carbohydrate antigen 19.9) levels in the cerebrospinal fluid (CSF) as well as by clinical status of the patient. Results: The follow-up of cytology and CA19.9 levels in the CSF showed dramatic improvement within 26 days followed by a biological relapse on Day +36. There was no evidence of local central nervous system toxicity. Three months later, neoplastic meningitis recurred and meningeal tumor infiltration was observed on magnetic resonance imaging. Six months after MTX-125IUdR treatment, the patient died. Conclusion: 125IUdR treatment proved to be feasible without acute neurological toxicity and seemed to have produced a biological response. This attempt provides the basis for designing prospective clinical trials.