title: Receptor-mediated radionuclide therapy with 90Y-DOTATOC in association with amino acid infusion: a phase I study.
abstract: The aim of this study was to determine the maximum tolerated dose of (90)Y-DOTATOC per cycle administered in association with amino acid solution as kidney protection in patients with somatostatin receptor-positive tumours. Forty patients in eight groups received two cycles of (90)Y-DOTATOC, with activity increased by 0.37 GBq per group, starting at 2.96 and terminating at 5.55 GBq. All patients received lysine +/- arginine infusion immediately before and after therapy. Forty-eight percent developed acute grade I-II gastrointestinal toxicity (nausea and vomiting) after amino acid infusion whereas no acute adverse reactions occurred after (90)Y-DOTATOC injection up to 5.55 GBq/cycle. Grade III haematological toxicity occurred in three of seven (43%) patients receiving 5.18 GBq, which was defined as the maximum tolerable activity per cycle. Objective therapeutic responses occurred. Five GBq per cycle is the recommended dosage of (90)Y-DOTATOC when amino acids are given to protect the kidneys. Although no patients developed acute kidney toxicity, delayed kidney toxicity remains a major concern, limiting the cumulative dose to ~25 Gy. The way forward with this treatment would seem to be to identify more effective renal protective agents, in order to be able to increase the cumulative injectable activity and hence tumour dose.
authors.affiliation: Division of Nuclear Medicine, European Institute of Oncology, via Ripamonti 435, 20141 Milan, Italy.
authors.forename: Lisa
authors.initials: L
authors.lastname: Bodei
authors.forename: Marta
authors.initials: M
authors.lastname: Cremonesi
authors.forename: Stefania
authors.initials: S
authors.lastname: Zoboli
authors.forename: Chiara
authors.initials: C
authors.lastname: Grana
authors.forename: Mirco
authors.initials: M
authors.lastname: Bartolomei
authors.forename: Paola
authors.initials: P
authors.lastname: Rocca
authors.forename: Maurizio
authors.initials: M
authors.lastname: Caracciolo
authors.forename: Helmut R
authors.initials: HR
authors.lastname: Mäcke
authors.forename: Marco
authors.initials: M
authors.lastname: Chinol
authors.forename: Giovanni
authors.initials: G
authors.lastname: Paganelli
mesh_terms: D000328:Adult; D000368:Aged; D000596:Amino Acids / Q000008:administration & dosage* / Q000009:adverse effects*; D014408:Biomarkers, Tumor / Q000378:metabolism; D001792:Blood Platelets / Q000528:radiation effects; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D005260:Female; D006454:Hemoglobins / Q000528:radiation effects; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000528:radiation effects; D008214:Lymphocytes / Q000528:radiation effects; D008297:Male; D020714:Maximum Tolerated Dose; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D009325:Nausea / Q000209:etiology; D009369:Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism / Q000532:radiotherapy* / Q000628:therapy; D015282:Octreotide / Q000008:administration & dosage / Q000009:adverse effects* / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011837:Radiation-Protective Agents / Q000008:administration & dosage / Q000009:adverse effects; D011874:Radiometry / Q000379:methods; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D017481:Receptors, Somatostatin / Q000378:metabolism; D051437:Renal Insufficiency / Q000209:etiology; D014839:Vomiting / Q000209:etiology; D015021:Yttrium Radioisotopes / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use
chemical_list: D000596:Amino Acids; D014408:Biomarkers, Tumor; D006454:Hemoglobins; D011837:Radiation-Protective Agents; D019275:Radiopharmaceuticals; D017481:Receptors, Somatostatin; D015021:Yttrium Radioisotopes; D015282:Octreotide; C106246:Edotreotide