Treatment With the Radiolabeled Somatostatin Analog [177Lu-DOTA0,Tyr3]Octreotate: Toxicity, Efficacy, and Survival

• Published in: Journal of clinical oncology Vol. 26; no. 13; pp. 2124 - 2130
• Main Authors: KWEKKEBOOM, Dik J, DE HERDER, Wouter W, KAM, Boen L, VAN EIJCK, Casper H, VAN ESSEN, Martijn, KOOIJ, Peter P, FEELDERS, Richard A, VAN AKEN, Maarten O, KRENNING, Eric P
• Format: Journal Article
• Language: English
• Published: Baltimore, MD American Society of Clinical Oncology 01.05.2008; Lippincott Williams & Wilkins
• Subjects: Adult; Aged; Aged, 80 and over; Biological and medical sciences; Carcinoid Tumor - diagnostic imaging; Carcinoid Tumor - mortality; Carcinoid Tumor - pathology; Chemical and Drug Induced Liver Injury; Disease-Free Survival; Female; Gastrointestinal Neoplasms - diagnostic imaging; Gastrointestinal Neoplasms - mortality; Gastrointestinal Neoplasms - pathology; Hematologic Diseases - chemically induced; Humans; Logistic Models; Male; Medical sciences; Middle Aged; Myelodysplastic Syndromes - chemically induced; Neuroendocrine Tumors - diagnostic imaging; Neuroendocrine Tumors - mortality; Neuroendocrine Tumors - pathology; Octreotide - adverse effects; Octreotide - analogs & derivatives; Octreotide - therapeutic use; Organometallic Compounds - adverse effects; Organometallic Compounds - therapeutic use; Pancreatic Neoplasms - diagnostic imaging; Pancreatic Neoplasms - mortality; Pancreatic Neoplasms - pathology; Proportional Hazards Models; Radionuclide Imaging; Radiopharmaceuticals - adverse effects; Radiopharmaceuticals - therapeutic use; Risk Assessment; Severity of Illness Index; Time Factors; Treatment Outcome; Tumors; Cancerology; Treatment; Radiolabelling; Toxicity; Analog; Treatment efficiency; Peptide hormone; Somatostatin; Neuropeptide; Survival
• ISSN: 0732-183X; 1527-7755
• DOI: 10.1200/JCO.2007.15.2553

Despite the fact that most gastroenteropancreatic neuroendocrine tumors (GEPNETs) are slow-growing, median overall survival (OS) in patients with liver metastases is 2 to 4 years. In metastatic disease, cytoreductive therapeutic options are limited. A relatively new therapy is peptide receptor radionuclide therapy with the radiolabeled somatostatin analog [(177)Lu-DOTA(0),Tyr(3)]octreotate. Here we report on the toxicity and efficacy of this treatment, performed in over 500 patients. Patients were treated up to a cumulative dose of 750 to 800 mCi (27.8-29.6 GBq), usually in four treatment cycles, with treatment intervals of 6 to 10 weeks. Toxicity analysis was done in 504 patients, and efficacy analysis in 310 patients. Any hematologic toxicity grade 3 or 4 occurred after 3.6% of administrations. Serious adverse events that were likely attributable to the treatment were myelodysplastic syndrome in three patients, and temporary, nonfatal, liver toxicity in two patients. Complete and partial tumor remissions occurred in 2% and 28% of 310 GEPNET patients, respectively. Minor tumor response (decrease in size > 25% and < 50%) occurred in 16%. Median time to progression was 40 months. Median OS from start of treatment was 46 months, median OS from diagnosis was 128 months. Compared with historical controls, there was a survival benefit of 40 to 72 months from diagnosis. Treatment with [(177)Lu-DOTA(0),Tyr(3)]octreotate has few adverse effects. Tumor response rates and progression-free survival compare favorably to the limited number of alternative treatment modalities. Compared with historical controls, there is a benefit in OS from time of diagnosis of several years.