Treatment of patients with gastro-entero-pancreatic (GEP) tumours with the novel radiolabelled somatostatin analogue [177Lu-DOTA(0),Tyr3]octreotate

Abstract

Medical treatment and chemotherapy are seldom successful in achieving objective tumour reduction in patients with metastatic neuroendocrine tumours. Treatment with the radiolabelled somatostatin analogue [(90)Y-DOTA(0),Tyr(3)]octreotide may result in partial remissions in 10-25% of patients. The newer analogue [DOTA(0),Tyr(3)]octreotate (octreotate) has a ninefold higher affinity for the somatostatin receptor subtype 2 as compared with [DOTA(0),Tyr(3)]octreotide. Also, labelled with the beta- and gamma-emitting radionuclide (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.

Fig. 1.

A–C Planar scans of the abdomen, 3 days after the injection of 200 mCi ¹⁷⁷Lu-octreotate in a patient with liver metastases of an operated neuroendocrine pancreatic tumour. A After the first treatment; B after the second treatment; C after the fourth treatment. Note the loss of intensity of uptake in the liver lesions (arrows in A). This sign virtually always indicates a tumour volume response. D, E CT scans of the same patient: before treatment (D) and 3 months after the last treatment (E). Tumour (arrows in D) is not demonstrated on E. Neither MRI nor octreoscan could demonstrate definite tumour deposits at that time

Fig. 2.

A, B MRI scans in a woman with hepatic metastases of a gastrinoma. Before treatment (A) she was inoperable because of the size and localization of the metastases. Three months after completion of her treatment with 800 mCi ¹⁷⁷Lu-octreotate she had a PR (B). Note also that the hypertrophy of the gastric wall (arrow in A) had diminished. Concomitantly, serum concentrations of gastrin (closed dots) and chromogranin-A (open dots) had decreased markedly (C). At 6 months the MRI showed no further regression. The patient underwent left partial hepatectomy and the two right-sided lesions were drained and injected with alcohol. MRI 3 months after surgery showed further regression of the right-sided lesions

Fig. 3.

Serum chromogranin-A concentrations during and after therapy in patients with PR, SD or PD. The reduction in the number of patients during the course of the follow-up was due to death or missing values. Note the logarithmic y-axis