Treatment of patients with gastro-entero-pancreatic (GEP) tumours with the novel radiolabelled somatostatin analogue [177Lu-DOTA0,Tyr3]octreotate

Abstract

177 Lu, it has proved very successful in achieving tumour regression in animal models. The effects of 177 Lu-octreotate therapy were studied in 35 patients with neuroendocrine gastro-entero-pancreatic (GEP) tumours who underwent follow-up for 3-6 months after receiving their final dose. Patients were treated with doses of 100, 150 or 200 mCi 177 Lu-octreotate, to a final cumulative dose of 600-800 mCi, with treatment intervals of 6-9 weeks. Nausea and vomiting within the first 24 h after administration were present in 30% and 14% of the administrations, respectively. WHO toxicity grade 3 anaemia, leucocytopenia and thrombocytopenia occurred after 0%, 1% and 1% of the administrations, respectively. Serum creatinine and creatinine clearance did not change significantly. The effects of the therapy on tumour size were evaluable in 34 patients. Three months after the final administration, complete remission was found in one patient (3%), partial remission in 12 (35%), stable disease in 14 (41%) and progressive disease in seven (21%), including three patients who died during the treatment period. Tumour response was positively correlated with a high uptake on the octreoscan, limited hepatic tumour mass and a high Karnofsky Performance Score. Because of the limited efficacy of alternative therapies, many physicians currently adopt an expectant attitude when dealing with patients with metastatic GEP tumours. However, in view of the high success rate of therapy with 177 Lu-octreotate and the absence of serious side-effects, we advocate its use in patients with GEP tumours without waiting for tumour progression.

Successful receptor-mediated radiation therapy of xenografted human midgut carcinoid tumour

“…The present study clearly shows that human midgut carcinoid xenografts can be cured by adequate radiation therapy with minimal adverse effects. Sstr-mediated radiation therapy using [ 177 Lu-DOTA 0 -Tyr 3 ]-octreotate in clinical series of patients with large tumour burden has not resulted in high rates of CR, most probably due to the administration of suboptimal amounts of radiopharmaceutical (Kwekkeboom et al, 2003). Our experiments show the importance of defining the amount of peptide required to achieve receptor saturation.…”

“…Previous experimental studies with xenografts have been performed using rat pancreatic acinar tumours carrying sstr, while the GOT1 model is an authentic human carcinoid with preserved phenotype (de Jong et al, 1998(de Jong et al, , 2001Kölby et al, 2001). In a recent series, patients with large NE tumour burden were treated with [ 177 Lu-DOTA 0 -Tyr 3 ]-octreotate and partial tumour regression was seen in 35% and complete remission in 3% (Kwekkeboom et al, 2003).…”

Metastatic Carcinoid Tumors: A Clinical Review

“…Higher tumor radiation can be achieved by application of 90 Y and 177 Lu, which are beta particles with a wider range of radiation and possibly a higher tumor uptake in neuroendocrine tumor lesions. The first reports of these modalities showed a tumor reduction in about 15%-30% of patients, with clinical benefit in up to 60% [63,64]. Observed toxicities were nausea and vomiting, hematological toxicities, and some renal function impairment.…”

Neuropeptide Y receptors in renal cell carcinomas and nephroblastomas

“…4,5 Another peptide hormone receptor family with a potential future role in this field is the NPY receptor family. It belongs to the G protein-coupled receptor superfamily and comprises various subtypes.…”

“…2,3 Moreover, targeted radiotherapy of these tumors with 90 Y-or 177 Lu-labeled somatostatin analogs is also promising. 4,5 Another peptide hormone receptor family with a potential future role in this field is the NPY receptor family. It belongs to the G protein-coupled receptor superfamily and comprises various subtypes.…”