Receptor-mediated radionuclide therapy with 90Y-DOTA-D-Phe1-Tyr3-Octreotide: preliminary report in cancer patients.
Recent advances in receptor mediated tumor imaging led to the development of a new somatostatin analogue DOTA-D-Phe1-Tyr3-Octreotide. This new compound, named DOTATOC, has shown high affinity for somatostatin receptors, stable labeling with yttrium-90 (90Y) and favourable biodistribution in patients. The aim of this work was to evaluate acute and late toxicity and the response rate in cancer patients administered 90Y-DOTATOC. Twenty patients received three equal i.v. injections of 90Y-DOTATOC. Cohorts of 5 patients were treated starting with 1.1 GBq per cycle in escalating dosage (0.4 GBq increments) in subsequent groups. No patients showed acute or delayed major adverse reactions up to the dose of 2.2 GBq of 90Y-DOTATOC per cycle (6.6 GBq total). Maximum tolerated dose has not been determined yet. One patient, after 4.4 GBq total dose, developed delayed kidney grade II toxicity. Complete and partial tumor mass reduction (CR and PR) was measured in 25% of patients along with 55% showing stable disease (SD) and 20% progressive disease (PD). These results indicate that high activities of 90Y-DOTATOC can be administered with low risk of myelotoxicity, although the radiation doses to the kidneys require careful consideration. Tumor doses were high enough in most cases to obtain objective therapeutic responses.
Paganelli
G
G
Division of Nuclear Medicine, European Institute of Oncology, Milan, Italy. dirmnu@ieo.cilea.it
Zoboli
S
S
Cremonesi
M
M
Mäcke
H R
HR
Chinol
M
M
D000328:Adult; D000368:Aged; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000532:radiotherapy*; D015282:Octreotide / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D010190:Pancreatic Neoplasms / Q000000981:diagnostic imaging / Q000532:radiotherapy; D019275:Radiopharmaceuticals / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D014018:Tissue Distribution; D014057:Tomography, X-Ray Computed; D015021:Yttrium Radioisotopes / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*
D019275:Radiopharmaceuticals; D015021:Yttrium Radioisotopes; D015282:Octreotide; C106246:Edotreotide