OctreoTher: ongoing early clinical development of a somatostatin-receptor-targeted radionuclide antineoplastic therapy.
OctreoTher ((90)Y-DOTA-D-Phe(1)-Tyr(3)-octreotide, a.k.a. (90)Y-SMT 487) consists of a somatostatin peptide analogue (Tyr(3)-octreotide), coupled with a complexing moiety (DOTA), and labeled with a tightly bound beta-emitter (yttrium-90). By targeting somatostatin receptor-positive tumors (as imaged by OctreaScan it may deliver a tumoricidal dose of radiation. Phase I clinical trials, conducted in patients with neuroendocrine tumors, established the safety and tolerability of the dose selected for further study and demonstrated the capacity of OctreoTher to deliver radiation doses to tumors that resulted in significant neuroendocrine tumor shrinkage. Novartis-sponsored phase II studies will soon begin to test the efficacy of OctreoTher in breast and small cell lung cancer. A fixed-dose regimen of 120 mCi/cycle x 3 cycles administered with concomitant amino acid infusion has been chosen for the study. Phase I data and published literature support that this fixed dose regimen will be safely tolerated.
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Novartis Pharmaceuticals Corporation, East Hanover, NJ 07936-1080, USA. chuck.smith@pharma.novartis.com
Liu
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Chen
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Schran
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Yeh
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Jamar
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Valkema
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Bakker
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Kvols
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Krenning
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Pauwels
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D000818:Animals; D001943:Breast Neoplasms / Q000378:metabolism / Q000532:radiotherapy; D018288:Carcinoma, Small Cell / Q000378:metabolism / Q000532:radiotherapy; D004307:Dose-Response Relationship, Radiation; D005260:Female; D006801:Humans; D007205:Indium Radioisotopes / Q000627:therapeutic use*; D008175:Lung Neoplasms / Q000378:metabolism / Q000532:radiotherapy; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009369:Neoplasms / Q000378:metabolism / Q000532:radiotherapy*; D018358:Neuroendocrine Tumors / Q000378:metabolism / Q000532:radiotherapy; D015282:Octreotide / Q000031:analogs & derivatives* / Q000627:therapeutic use; D019275:Radiopharmaceuticals / Q000627:therapeutic use*; D017481:Receptors, Somatostatin / Q000378:metabolism; D013004:Somatostatin / Q000031:analogs & derivatives; D015021:Yttrium Radioisotopes / Q000627:therapeutic use*
D007205:Indium Radioisotopes; D019275:Radiopharmaceuticals; D017481:Receptors, Somatostatin; D015021:Yttrium Radioisotopes; D013004:Somatostatin; C081788:pentetreotide; D015282:Octreotide; C106246:Edotreotide