Toxicity And Efficacy Profiles Of Intrathecal Injection Of I-131 Nal Via Intraventricular (Ivent) Or Intralumbar (Iiumb) Route For Leptomeningeal Metastases (Lm) Therapy.

1549 Background: LM is a fatal complication occurring in up to 30% of cancer patients. Intrathecal chemotherapy of LM is limited by diffusion while external beam irradiation is limited by neurotoxicity. Radioiodine I-131 may serve as a ablating agent because of its radiations transverse the meningeal thinkness but spare distant underlying nervous tissues. Two phase I studies are designed to determine MTD and to evaluate potential toxicity and efficacy of intrathecal I-131 sodium iodide (NaI) injected via IVent or the ILumb route. Methods: The IVent or Ilumb protocols each accured 5 groups of patients with cytology-confirmed LM from solid tumors. An injection of 15, 30, 60, 90 or 120 mCi of I-131 NaI was performed after thyroid blockade (Lugol solution and perchlorate), via an Ommaya reservoir (IVent) or lumbar puncture (ILumb). Patients underwent whole-body scintigraphy for biodistribution and radiation dosimetry. Follow-up studies consisted of serial CSF cytology, neuropsychology, ophthalmology, and serum tests (TSH and CBC) to 6 months. Results: The IVent and Ilumb studies accured 16 and 15 patients respectively with LM from melanoma, lung, breast and other tumors (13, 8, 6 and 4 of 31 patients). Because of re-entry into the protocols, one patient received a total of 407 mCi; the maximum radiation absorbed doses were estimated at 3716 cGy in the ventricular CSF and 54 cGy in the red marrow. No treatment-related NCI-Grade II/III/IV neurologic, hematologic or thyroid toxicity is noted. Transient improvements up to 6 weeks are noted in neuropsychologic tests (5/16 and 5/15), ophthalomologic test (3/16 and 1/15) and CSF cytology conversion (to negative) in 5/16 and 4/15 patients, respectively. Electrophysiology tests of 2 patients demonstrated normalization of P37 waves measured by somatosensory evoked potentials along with neuropsychologic test improvements. Conclusions: The MTD has not been reached up to 120 mCi on either the IVent or Ilumb protocol. Intrathecal I-131 NaI is likely to be efficacious to eradicate tumors in the CSF for LM therapy. Because of the low toxicity and likely efficacy, a phase II study with higher dosages is needed to fully explore therapeutic potentials of intrathecal I-131 NaI. No significant financial relationships to disclose.