Treatment of neoplastic meningitis by targeted radiation using 131I-radiolabelled monoclonal antibodies

• Published in: Journal of neuro-oncology 1998-06, Vol.38 (2-3), p.225-232
• Main Authors: Coakham Hugh B, Kemshead, John T
• Format: Article
• Language: English
• Subjects: Catheters; Central nervous system; Cerebrospinal fluid; Immunoreactivity; Leukemia; Medical prognosis; Meningitis; Metastatic seeding; Monoclonal antibodies; Nervous system diseases; Patients; Radioisotopes; Scintigraphy; Survival; Systemic diseases; Toxicity; Tumors; Ventricle
• ISSN: 0167-594X; 1573-7373
• DOI: 10.1023/A:1005996606073

Between 1984 and 1993, monoclonal antibodies (MAbs) radiolabelled with 131I were administered into the CSF of 52 patients with neoplastic meningitis (meningosis) with progressive disease despite active conventional therapy. Selection of MAbs was based on immunoreactivity with patients' tumour and lack of binding to normal central nervous system (CNS) tissue.Following full clinical assessment and neuro-imaging which included isotope flow study of CSF pathways, 131I-MAb was administered via a ventricular access device, lumbar catheter or both. Radioisotope activity varied from 25 mCi to 160 mCi in adults. Dose escalation was carried out and some patients received multiple doses.Distribution of 131I-MAb and clearance kinetics were derived from serial scintigraphy and CSF/blood sampling. Evidence of localisation to tumour was frequently observed. Toxicity was minimal and easily treated, although one death occurred, possibly due to a seizure.The best results were obtained in primitive neuroectodermal tumour (n=22), where 53% of evaluable cases had responses and 11% had stable disease, adults responding better than children. Three exceptional survivals have been recorded; 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 condition for 8 years.The mean survival of responders was 39 months and non-responders 4 months. In the total series, 50% of patients survived for at least one year with 2 long term survivors. CSF therapy with 131I-MAb appears to be valuable as a single agent or when used in combination with other modalities.Results of treating leukaemia and carcinoma cases suggest that re-seeding into the CSF compartment from active systemic disease may account for early relapse in the CNS. One carcinoma case with no apparent systemic disease made a remarkable response and survival for 4 years following a single treatment.Neoplastic meningitis generally carries a dismal prognosis. The results obtained in this initial trial are sufficiently encouraging to stimulate further attempts at CSF therapy with 131I-MAbs.