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The Quarterly Journal of Nuclear Medicine and Molecular imaging 2010 February;54(1):92-9


lingua: Inglese

Individualized peptide-related-radionuclide-therapy concept using different radiolabelled somatostatin analogs in advanced cancer patients

Gabriel M., Andergassen U., Putzer D., Kroiss A., Waitz D., Von Guggenberg E., Kendler D., Virgolini I. J.

Department of Nuclear Medicine, Innsbruck Medical University, Innsbruck, Austria


Aim. Over the last decade, somatostatin (SST) receptor (R)-positive tumors have been treated using either 90Y-DOTA-TOC, 177Lu-DOTA-TATE or 90Y-DOTA-LAN/177Lu-DOTA-LAN, at the Innsbruck Medical University. This report presents data from the evaluation of the initial 100 patients receiving receptor mediated radionuclide therapy (PRRT) according to our protocol.
Methods. One-hundred patients with SSTR-positive tumors were treated (36 female, 64 male; mean age, 58 years; range, 13 to 84 years), including 68 patients with neuroendocrine tumors (NET), and patients with other non-neuroendocrine tumors, e.g. patients with radioiodine-negative thyroid carcinoma, refractory to conventional treatment modalities. Patients were selected based on high SSTR expression as assessed by 68Ga-DOTA-TOC as first choice tracer for patients with NET, or 68Ga-DOTA-LAN for patients with other tumor entities, or if the 68Ga-DOTA-TOC PET was negative. Following positron emission tomography (PET), individual dosimetry was regularly performed using 111In-labeled compounds. Therapy cycles were repeated every 10 weeks using either 90Y-DOTA-TOC (3.7 GBq, 3-5 cycles) or 177Lu-DOTA-TATE (7.4 GBq, 3-4 cycles). Thirteen patients received both and 5 patients even 3 different therapeutic compounds. Each patient received an amino acid solution (arginin, lysine) to reduce the kidney dose. Between the radioactive cycles a long-acting SST analog was applied. Dosages were individually adapted depending on several disease related factors.
Results. Overall, following PRRT partial remission (PR) was observed in 23 patients (23 %), minor remission (MR) in 10 (10 %), stable disease (SD) in 42 patients (42 %). Although 25 patients (25 %) showed progressive disease (PD), palliative care was provided in most of these patients. In the group treated with 90Y-DOTA-TOC, 12 patients showed PR, 3 MR, 32 SD and 13 had PD. In the group of patients treated with 177Lu-DOTA-TATE, PR was observed in 15 patients, MR in 8, SD in 19 and PD in 13 patients. Severe side effects (WHO Grad 3 and 4) were seen in only 6 % of patients. Severe long-term nephrotoxicity was observed in none of the patients. These adverse reactions were especially seen in patients who were treated with high doses per cycle, in patients pre-treated with chemotherapy and in patients with low clinical performance.
Conclusion. PRRT with differently labelled tracers (Y-90 or Lu-177) and different SST-analogs is generally well tolerated without serious side effects. These results favour the combined use of radiolabeled SST analogs providing a customized tumour targeting for size reduction and improvement of quality-of-life. Extended time intervals and reduced individual doses make sense in patients with advanced tumor stages, in case of moderate SSTR-expression, and in patients with higher age.

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