Tumor response and clinical benefit in neuroendocrine tumors after 7.4 GBq (90)Y-DOTATOC.
The aim of this prospective phase II study was to evaluate the tumor response of neuroendocrine tumors to high-dose targeted irradiation with 7.4 GBq/m(2) of the radiolabeled somatostatin analog (90)Y-1,4,7,10-tetra-azacyclododecan-4,7,10-tricarboxy-methyl-1-yl-acetyl-D-Phe-Tyr(3)-octreotide (DOTATOC). In addition, we investigated the clinical benefit of (90)Y-DOTATOC regarding the malignant carcinoid syndrome and tumor-associated pain.


METHODS
Thirty-nine patients (mean age, 55 y) with progressive neuroendocrine gastroenteropancreatic and bronchial tumors were included. The treatment consisted of 4 equal intravenous injections of a total of 7.4 GBq/m(2) (90)Y-DOTATOC, administered at intervals of 6 wk. After each treatment cycle, a standardized clinical benefit assessment using the National Cancer Institute grading criteria (NCI-CTC) was performed.


RESULTS
The objective response rate according to World Health Organization (WHO) criteria was 23%. For endocrine pancreatic tumors (13 patients), the objective response rate was 38%. Complete remissions were found in 5% (2/39), partial remissions in 18% (7/39), stable disease in 69% (27/39), and progressive disease in 8% (3/39). A significant reduction of clinical symptoms could be found in 83% of patients with diarrhea, in 46% of patients with flush, in 63% of patients with wheezing, and in 75% of patients with pellagra. The overall clinical benefit was 63%. All responses (both clinical benefit and WHO response) were ongoing for the duration of follow-up (median, 6 mo; range, 2-12 mo). Side effects were grade 3 or 4 (NCI-CTC) lymphocytopenia in 23%, grade 3 anemia in 3%, and grade 2 renal insufficiency in 3%.


CONCLUSIONS
High-dose targeted radiotherapy with 7.4 GBq/m(2) (90)Y-DOTATOC is a well-tolerated treatment for neuroendocrine tumors, with remarkable clinical benefit and objective response.
Waldherr
Christian
C
PET Center, Institute of Nuclear Medicine, University Hospital, University of Basel, Basel, Switzerland.
Pless
Miklos
M
Maecke
Helmut R
HR
Schumacher
Tilmann
T
Crazzolara
Armin
A
Nitzsche
Egbert U
EU
Haldemann
Andreas
A
Mueller-Brand
Jan
J
D002276:Carcinoid Tumor / Q000532:radiotherapy; D006801:Humans; D008875:Middle Aged; D018358:Neuroendocrine Tumors / Q000000981:diagnostic imaging / Q000401:mortality / Q000532:radiotherapy*; D015282:Octreotide / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D010148:Intractable Pain / Q000188:drug therapy; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000627:therapeutic use*; D015021:Yttrium Radioisotopes / Q000009:adverse effects / Q000627:therapeutic use*
D019275:Radiopharmaceuticals; D015021:Yttrium Radioisotopes; D015282:Octreotide; C106246:Edotreotide