title: Interferon and meta-iodobenzylguanidin combinations in the treatment of metastatic carcinoid tumours.
abstract: Interferon (IFN) and meta-iodobenzylguanidin (MIBG) are active in metastatic carcinoids. In a phase II study, we evaluated the effect upon diagnostic 131I-MIBG uptake and the clinical response of the combination. 131I-MIBG scintigraphy was performed prior to treatment, after 8 weeks of IFN and after unlabelled MIBG. The tumour over non-tumour (T/NT) ratios were quantitatively determined by comparing counts in the centre of the tumour (liver metastases) with those in an adjacent area of normal liver uptake (T/NT1) and with abdominal background area (T/NT2). The T/NT1 ratio showed an increase of >10% in only four out of 21 patients (19%) after IFN (P = 0.178) and significantly more often in nine out of 18 patients (50%) after unlabelled MIBG (P = 0.016). The absolute uptake in tumour deposits was also increased if compared with the abdominal background (T/NT2: 23% increase after IFN and 83% increase after unlabelled MIBG). The combination produced 91% of patients with stable disease (using World Health Organisation criteria) at computed tomography scan and a biochemical response (a reduction of at least 50% in urinary 5-hydroxyindolacetic acid excretion) in 39%. IFN-alpha did not significantly improve tumour retention of 131I-MIBG. In contrast, unlabelled MIBG significantly improved biodistribution and tumour uptake in 83%. A synergistic effect was not seen.
authors.affiliation: Department of Gastroenterology, Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands. j.zuetenhorst@nki.nl
authors.forename: J M
authors.initials: JM
authors.lastname: Zuetenhorst
authors.forename: R A
authors.initials: RA
authors.lastname: Valdes Olmos
authors.forename: M
authors.initials: M
authors.lastname: Muller
authors.forename: C A
authors.initials: CA
authors.lastname: Hoefnagel
authors.forename: B G
authors.initials: BG
authors.lastname: Taal
mesh_terms: D019797:3-Iodobenzylguanidine / Q000008:administration & dosage; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002276:Carcinoid Tumor / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000556:secondary*; D018450:Disease Progression; D005260:Female; D006801:Humans; D006897:Hydroxyindoleacetic Acid / Q000652:urine; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage; D007414:Intestinal Neoplasms / Q000188:drug therapy / Q000473:pathology; D008113:Liver Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000556:secondary*; D008175:Lung Neoplasms / Q000188:drug therapy / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000473:pathology; D015996:Survival Rate; D014055:Tomography, Emission-Computed
chemical_list: D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D019797:3-Iodobenzylguanidine; D006897:Hydroxyindoleacetic Acid