Abstract
Between 1984 and 1993, monoclonal antibodies (MAbs) radiolabelled with 1 3 1I 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, 1 3 1I-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 1 3 1I-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 1 3 1I-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 1 3 1I-MAbs.
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References
Coakham HB, Garson JA, Brownell DB, Allan PM, Harper EI, Lane EB, Kemshead JT: Use of monoclonal antibody panel to identify malignant cells in CSF. Lancet 8386: 1095–1098, 1984
Coakham HB, Garson JA, Allan PM, Harper EI, Lane EB, Brownell DB, Kemshead JT: The immunohistological diagnosis of central nervous system tumours using monoclonal antibodies. J Clin Pathol 38: 165–173, 1985
Richardson RB, Davies AG, Bourne SP, Staddon GE, Jones DE, Kemshead JT, Coakham HB: Radioimmunolocalisation of human brain tumours: Biodistribution of radiolabelled monoclonal antibody UJ13A. Eur J Nucl Med 12: 313–320, 1986
Zalutsky MR, Moseley RP, Coakham HB, Coleman RE, Bigner DD: Pharmacokinetics and tumour localisation of 131I labelled anti-tenascin monoclonal antibody 81C6 in patients with gliomas and other intracranial malignancies. Cancer Res 49: 2807–2813, 1989
Vaughan AT, Anderson P, Dykes PW, Chapman CE, Bradwell AR: Limitations to the killing of tumours using radiolabelled antibodies. Br J Radiol 60: 567, 1987
Coakham HB, Richardson RB, Davies AG, Bourne SP, Eckert H, Kemshead JT: Neoplastic meningitis from a pineal tumour treated by antibody-guided irradiation via the intrathecal route. Br J Neurosurg 2: 199–209, 1988
Lashford LS, Davies GA, Richardson TB, Bourne SP, Bullimore JA, Ekert H, Kemshead JT, Coakham HB: A pilot study of 131I monoclonal antibodies in the therapy of leptomeningeal tumours. Cancer 61: 857–868, 1988
Moseley RP, Davies AG, Richardson RB, Zalutsky M, Carrell S, Fabre J, Slack N, Bullimore J, Pizer B, Papanastassiou V, Kemshead JT, Coakham HB, Lashford LS: Intrathecal administration of 131I radiolabelled monoclonal antibodies as a treatment for neoplastic meningitis. Br J Cancer 62: 637–642, 1990
Pizer BL, Papanastassiou V, Hancock J, Cassano W, Coakham HB, Kemshead JT: A pilot study of targeted radiotherapy in the treatment of central nervous system leukaemia in children. Br J Haem 77: 466–472, 1991
Moseley RP, Benjamin JC, Ashpole RD, Sullivan NM, Bullimore JA, Coakham HB, Kemshead JT: Carcinomatous meningitis: Antibody guided therapy with 131I HMFG1. J Neurol Neurosurg Psychiat 54: 260–265, 1991
Taylor-Papadimitriou J, Peterson JA, Arklie J, Burchall J, Ceriani RJ, Bodmer WF: Monoclonal antibodies to epithelium specific components of the human milk fat globule membrane. Int J Cancer 28: 17–21, 1981
Moseley RP, Oge K, Shafqat S, Moseley CM, Sullivan N, Badley RA, Burchell J, Taylor Papadimitriou J, Coakham HB: HMFG1 antigen: A new CSF marker for carcinomatous meningitis. Int J Cancer 44: 440–444, 1989
Benjamin JC, Moss T, Moseley RP, Maxwell R, Coakham HB: Cerebral distribution of immunoconjugate after treatment for neoplastic meningitis using an intrathecal radiolabelled monoclonal antibody. Neurosurgery 25: 253–258, 1989
Ongerboer de Visser BW, Somers R, Nooyen WH, Van Heerde P, Augustinus AM, McVie JG: Intraventricular methotrexate therapy of leptomeningeal metastasis from breast carcinoma. Neurology 33: 1565–1572, 1983
Levin VA, Vestrys PS, Edwards MS: Improvement in survival produced by sequential therapies in the treatment of recurrent medulloblastoma. Cancer 51: 1364–1370, 1983
Smith DB, Moseley RP, Begent RH, Coakham HB, Glaser MG, Dewhurst S, Kelly A, Bagshawe KD: Quantitative distribution of 131I labelled monoclonal antibodies administered by the intra-ventricular route. Eur J Cancer 26(2): 129–136, 1990
Richardson RB, Kemshead JT, Davies AG, Staddon GE, Jackson PC, Coakham HB, Lashford LS: Dosimetry of intrathecal iodine 131 monoclonal antibody in cases of neoplastic meningitis. Eur J Nucl Med 17: 42–48, 1989
Bigner DD, Brown M, Coleman E, Friedman HS, McClendon RE, Bigner SH, Zhao X-G, Wikstrand CJ, Pegrum CN, Kerberg T, Zalutsky MR: Phase I studies of treatment of malignant gliomas and neoplastic meningitis with 131I-radiolabelled monoclonal antibodies anti-tenascin 81C6 and antichondroitin proteglycan sulphate Mel-14 F(ab′)2 – a preliminary report. J Neuro-Oncol 24: 109–122, 1995
Carrie C, Lasset C, Alapetite C, Haie-Meder C, Hoffstetters S, Demaille M-C et al.: Multivariate analysis of prognostic factors in adult patients with medulloblastoma. Cancer 74: 2352–2360, 1994
Johnson DL, McCabe MA, Nicholson D et al.: Quality of survival in young children with medulloblastoma. J Neurosurg 80: 1004–1010, 1994
Allan PM, Garson JA, Harper EI, Coakham HB, Brownell B, Kemshead JT: Biological characterisation and clinical applications of a monoclonal antibody recognising an antigen restricted to neuroectodermal tissues. Int J Cancer 31: 591–598, 1983
Bourne S, Pemberton L, Moseley R, Lashford LS, Coakham HB, Kemshead JT: Monoclonal antibodies M340 and UJ181.4 recognise antigens associated with primitive neuroectodermal tumours. Hybridoma 8(4): 415–426, 1989
Carrel S, Acciolla RS, Carmagnola AL, Mach JP: A common melanoma associated antigen detected by monoclonal antibody. Cancer Res 40: 2523–2528, 1980
Bourdon MA, Wikstrand CJ, Furthmayr H, Matthews TJ, Bigner DD: Human glioma-mesenchymal extracellular matrix antigen defined by monoclonal antibody. Cancer Res 43: 2796–2805, 1983
Dalchan R, Fabre JW: Identification with a monoclonal antibody of a predominantly B lymphocyte-specific determinant of the human leukocyte common antigen. J Exp Med 153: 753–765
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Coakham, H.B., Kemshead, J.T. Treatment of neoplastic meningitis by targeted radiation using 131I-radiolabelled monoclonal antibodies. J Neurooncol 38, 225–232 (1998). https://doi.org/10.1023/A:1005996606073
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DOI: https://doi.org/10.1023/A:1005996606073