Hematological toxicity of combined 177Lu-octreotate radiopeptide chemotherapy of gastroenteropancreatic neuroendocrine tumors in long-term follow-up

Abstract

Background: The combination of radiopeptide therapy [peptide receptor radionuclide therapy (PRRT)] with radiosensitizing chemotherapy of gastroenteropancreatic neuroendocrine tumors (GEP NETs) may improve efficacy, but has the potential to increase myelotoxicity. In a prospective clinical study of GEP NET patients treated with (177)Lu-octreotate PRRT in combination with capecitabine and temozolomide, as a prelude to a planned Australasian Gastro-Intestinal Trials Group (AGITG) international randomized controlled trial, we characterized the incidence and degree of hematological toxicity.

Materials and methods: Well-differentiated progressive metastatic GEP NETs in 65 patients were treated with 4 cycles of 7.8 GBq (177)Lu-octreotate, 1,650 mg/m(2) capecitabine (n = 28) and 1,500 mg/m(2) capecitabine with 200 mg/m(2) temozolomide (n = 37), and monitored for hematological toxicity over a 5-year period.

Results: Short-term, self-limited hematological toxicity grade 3/4 comprised anemia in 1 patient (3.5%) in the 28 patient-cohort of patients treated with (177)Lu-octreotate and capecitabine. One of these patients (3.5%) later developed significant anemia and one developed thrombocytopenia (3.5%) over a median follow-up of 60 months (SD 20). The incidence of short-term grade 3/4 reversible myelosuppression in 37 patients after (177)Lu-octreotate/capecitabine/temozolomide was zero. Long- term follow-up for a median of 36 months (SD 11) showed significant thrombocytopenia in 2.7% and neutropenia in 2.7% of the patients and anemia in 10.8% of the patients (n = 4). The 3-year median hemoglobin and platelet and neutrophil counts trended downwards, but remained within normal ranges. Two patients in this cohort developed myelodysplastic syndrome.

Conclusion: The modest reversible hematological toxicity of PRRT of GEP NETs is not significantly increased by the addition of radiosensitizing chemotherapy with capecitabine and temozolomide in combination with (177)Lu-octreotate, which has the potential to enhance the efficacy of radiopeptide therapy.