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 131 I-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 ðP ¼ 0:178Þ and significantly more often in nine out of 18 patients (50%) after unlabelled MIBG ðP ¼ 0:016Þ. 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-a did not significantly improve tumour retention of 131 I-MIBG. In contrast, unlabelled MIBG significantly improved biodistribution and tumour uptake in 83%. A synergistic effect was not seen.

Chromogranin A as an Alternative to 5-Hydroxyindoleacetic Acid in the Evaluation of Symptoms during Treatment of Patients with Neuroendocrine Tumors

“…In the current analysis, we focused on those HRQL outcomes that were hypothesized to be particularly relevant to patients with carcinoid syndrome, namely physical functioning, overall HRQL and diarrhea. Two questions were added to evaluate specific carcinoid symptoms, namely flushes and abdominal pain [9, 13, 14]. All scores were linearly transformed to a 0–100 scale.…”

Metastatic Carcinoid Tumors: A Clinical Review

“…A reduction in tumor size is reported in a small minority of patients (about 10%-20%), and the administration of higher dosages of IFN does not increase this response rate. Development of antibodies during treatment with IFN is described in about 5%-20% of patients and seems to be higher with the use of IFN-α2a (Roferon-A ® ; Roche Laboratories, Inc.; Nutley, NJ) than with IFN-α2b (Intron-A ® ; Schering-Plough Corporation; Kenilworth, NJ) [54,55]. The role of these antibodies is controversial.…”

Dual-Targeted Extracellular Vesicles to Facilitate Combined Therapies for Neuroendocrine Cancer Treatment

“…Neuroendocrine (NE) cancers arising from cells within the neuroendocrine system are often metastatic at the time of initial diagnosis [1], and patients with untreated, isolated NE tumor (NET) liver metastases have a <30% five-year survival rate. Several chemotherapies, such as everolimus, sunitinib, resveratrol, octreotide, thailandepsin-A and AB3 [2][3][4][5][6][7][8][9][10][11][12][13][14][15], have been investigated for NET treatment, but their therapeutic efficacy is limited. The peptide receptor radionuclide therapy (PRRT, Lutathera) that combines endoradiotherapy ( 177 Lu-DOTA-TATE) has been approved to treat somatostatin receptor (SSTR) positive gastroenteropancreatic NETs [16,17], but it has short radiopharmaceutical shelf life, reduces active concentration over time due to the decay of 177 Lu, and has a poor therapeutic impact on rapidly proliferating NE cancers.…”