Carcinoid Therapy Clinical Applications
Conventional therapy such as chemotherapy or radiation therapy have a limited role in the treatment of these tumors. MIBG labeled with 131I was initially employed. In recent years several peptides analogs of somatostatin, which bind to sst2 and sst5 cell receptors labeled either with 90Y and 177Lu, have been used to treat carcinoid tumors and their metastasis. Results have been encouraging to stabilize the tumoral process though rarely to cure the disease (1-3). This is due to large tumoral masses at the moment of diagnosis.
In order to undertake the radionuclide therapy, a diagnostic MIBG or Somastostatine Analog procedure is required to demonstrate significant increased uptake in lesions that justify giving a therapeutic dose. Ideally a biopsy should confirm the diagnosis as well.
Recent reports have demonstrated the benefits of 177Lu-Dotatate therapy, including gastrointestinal and bronchial tumors (4).
Claringbold et al in 33 patients with biopsy-proven unresectable neuroendocrine
tumours, positive 111In-octreotide scintigraphy and progressive disease
measurable by CT/MRI were treated with four cycles of 7.8 GBq 177Lu-octreotate
8-weekly, with 14 days of 1,650 mg/m2 capecitabine per day. Minimal transient
myelosuppression at 3–4 weeks caused grade 3 thrombocytopenia in one patient but
no neutropenia.
Nephrotoxicity was absent.
"Survival at
1 and 2 years was 91% (95% CI 75–98%) and 88% (95% CI 71–96%), respectively. The
addition of capecitabine radiosensitizing chemotherapy led to an ORR of 24% PR
and 70% minor response or SD in patients with progressive metastatic NETs.
Tumour control and stabilization of disease was obtained in 94% of these
patients."
References:
1) Diez L, Mitjavila M, Tumores Neuroendocrinos: Estudios con meta-yodo-bencil-guanidina, p: 549-561 in: Medicina Nuclear Aplicaciones Clínicas. Eds: I. Carrio - P. González. Editorial Masson, Barcelona España, 2003.
2) Lisa Bodei, Marta Cremonesi, Chiara Grana, Paola Rocca, Mirco Bartolomei, Marco Chinol, Giovanni Paganelli. Receptor radionuclide therapy with 90Y-[DOTA]0-Tyr3-octreotide (90Y-DOTATOC) in neuroendocrine tumours. Eur J Nucl Med Mol Imaging (2004) 31:1038–1046.
3) Kwekkeboom Dik J et al. Treatment With the Radiolabeled Somatostatin Analog [177Lu-DOTA0,Tyr3]Octreotate: Toxicity, Efficacy, and Survival. J Clin Oncol 2008; 26: 2124-2130.
4) Martijn van Essen et al. Salvage Therapy with 177Lu-Octreotate in Patients with Bronchial and Gastroenteropancreatic Neuroendocrine TumorsJ Nucl Med 2010; 51:383–390.
5)
Phillip G. Claringbold, Paul A. Brayshaw, Richard A. Price and J. Harvey Turner.
Phase II study of radiopeptide 177Lu-octreotate and capecitabine therapy of
progressive disseminated neuroendocrine tumours. Eur J Nucl Med Mol Imaging
(2011) 38:302–311.