TREATMENT OF NEOPLASTIC MENINGITIS BY TARGETED RADIATION USING I-131 RADIOLABELED MONOCLONAL-ANTIBODIES - RESULTS OF RESPONSES AND LONG-TERM FOLLOW-UP IN 40 PATIENTS

Between 1984 and 1993, monoclonal antibodies (MAbs) radiolabelled with I-131 were administered into the CSF of 52 patients with neoplastic m eningitis (meningosis) with progressive disease despite active convent ional therapy. Selection of MAbs was based on immunoreactivity with pa tients' tumour and lack of binding to normal central nervous system (C NS) tissue. Following full clinical assessment and neuro-imaging which included isotope flow study of CSF pathways, I-131-MAb was administer ed via a ventricular access device, lumbar catheter or both. Radioisot ope activity varied from 25 mCi to 160 mCi in adults. Dose escalation was carried out and some patients received multiple doses. Distributio n of I-131-MAb and clearance kinetics were derived from serial scintig raphy and CSF/blood sampling. Evidence of localisation to tumour was f requently observed. Toxicity was minimal and easily treated, although one death occurred, possibly due to a seizure. The best results were o btained in primitive neuroectodermal tumour (n = 22), where 53% of eva luable cases had responses and 11% had stable disease, adults respondi ng better than children. Three exceptional survivals have been recorde d; one patient leads a normal life at 10 years 11 months, one case is alive and normal at 3 years, 2 months. a third case survived in good c ondition for 8 years. The mean survival of responders was 39 months an d non-responders 4 months. In the total series, 50% of patients surviv ed for at least one year with 2 long term survivors. CSF therapy with I-131-MAb appears to be valuable as a single agent or when used in com bination with other modalities. Results of treating leukaemia and carc inoma cases suggest that re-seeding into the CSF compartment from acti ve systemic disease may account for early relapse in the CNS. One carc inoma case with no apparent systemic disease made a remarkable respons e and survival for 4 years following a single treatment. Neoplastic me ningitis generally carries a dismal prognosis. The results obtained in this initial trial are sufficiently encouraging to stimulate further attempts at CSF therapy with I-131-MAbs.