title: Long-term efficacy of low activity meta-[131I]iodobenzylguanidine therapy in patients with disseminated neuroendocrine tumours depends on initial response.
abstract: BACKGROUND
  meta-[131I]Iodobenzylguanidine (131I-MIBG) has been used to treat patients with disseminated neuroendocrine tumours (NET). However, so far there is limited information related to the efficacy of this agent beyond the normal 6-month assessment period. Before we can assume that such treatment would be beneficial to patients with these tumours the outcome of the patients over a longer time course should be determined. In many centres financial or radiation protection constraints mean that lower activities of 131I-MIBG have to be used at each administration, therefore instead of giving a single administration of a higher activity 131I-MIBG a series of multiple lower activity administrations are used.
  
  
  METHODS
  The case records of 25 patients who had received 131I-MIBG over a 4-year period, from 1 June 1997 to 30 June 2001, were reviewed. Overall time of clinical follow-up range from 1 to 60 months, with a mean of 16 months). There were 16 female and nine male patients (mean age 55.6 years; range, 30-79 years). Most of patients had carcinoid (17), two had phaeochromocytoma, two gastrinoma and two an undifferentiated NET, one had malignant paraganglioma and one had medullary cell carcinoma of the thyroid. All had avid uptake for 123I-MIBG on diagnostic scanning. The minimum number of treatments received was 1 in 4 patients (with activities of 2.0 to 3.4 GBq); the maximum was 11 treatments (with cumulative activities as high as 29.1 GBq). Treatment was given using an infusion pump and was normally repeated at 12- to 16-week intervals (mean number of treatments per patient, 4). Response to therapy was determined by changes in the size of the tumour on computed tomography and/or magnetic resonance imaging using the response evaluation criteria in solid tumours (RECIST). Toxicity was measured using blood and urine tests of renal, hepatic, thyroid and bone marrow function. The median time from the last treatment to progression of disease and death (if applicable) was also calculated.
  
  
  RESULTS
  No significant or long-lasting toxicity was encountered. At 6 months after the patient's last treatment, 18 patients (72%) had no evidence for progression. Twelve months after their last treatment 12 (48%) patients had no evidence for progression. At 18 months after the patient's last treatment, only seven patients (28%) had no progression of their disease. Overall, the median progression-free survival was 15 months. In those patients with stability or response at 6 months there was a prolonged progression-free survival and overall survival. In those with progression of disease at 6 months, at the 6-month assessment point, there had been four deaths (16%), at 12 months, there were three additional cancer deaths and finally at 18 months, there were a further five deaths. The median survival was 18 months. In those patients who died the mean time interval between disease progression and death was 4.6 months (range 0-12 months).
  
  
  CONCLUSIONS
  Of the patients treated with low-activity 131I-MIBG 68% had significant benefit for at least 6 months post-treatment. In these patients with progressive and extensive disease this technique provided prolonged progression-free and overall survival with minimal side effects especially if an initial response to treatment was seen.
authors.affiliation: Neuroendocrine Tumour Clinic, Royal Free Hospital, London UK. j.buscombe@medsch.ucl.ac.uk
authors.forename: John R
authors.initials: JR
authors.lastname: Buscombe
authors.forename: Jaroslaw B
authors.initials: JB
authors.lastname: Cwikla
authors.forename: Martyn E
authors.initials: ME
authors.lastname: Caplin
authors.forename: Andrew J W
authors.initials: AJ
authors.lastname: Hilson
mesh_terms: D019797:3-Iodobenzylguanidine / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009377:Multiple Endocrine Neoplasia / Q000453:epidemiology* / Q000532:radiotherapy*; D018358:Neuroendocrine Tumors / Q000453:epidemiology* / Q000532:radiotherapy*; D019275:Radiopharmaceuticals / Q000627:therapeutic use; D011879:Radiotherapy Dosage; D012189:Retrospective Studies; D018570:Risk Assessment / Q000379:methods*; D012307:Risk Factors; D016896:Treatment Outcome
chemical_list: D019275:Radiopharmaceuticals; D019797:3-Iodobenzylguanidine