Concomitant 177Lu-DOTATATE and capecitabine therapy in malignant paragangliomas

Madhav Prasad Yadav,Chandrasekhar Bal,Sanjana Ballal

doi:10.1186/s13550-019-0484-y

Madhav Prasad Yadav, Chandrasekhar Bal + Show 1 more

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https://doi.org/10.1186/s13550-019-0484-y

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Journal: EJNMMI research	Publication Date: Feb 6, 2019
Citations: 39	License type: open-access

Affiliation: All India Institute of Medical Sciences

Abstract

BackgroundThe role of concomitant peptide receptor radionuclide therapy (PRRT) and capecitabine therapy has shown benefit in gastroenteropancreatic neuroendocrine tumors. However, data reporting its role in paraganglioma (PGL) patients is lacking. The aim of this study was to evaluate the role of combined capecitabine and 177Lu-DOTATATE in malignant PGL patients.MethodsIn this retrospective, single-institutional, single-arm, observational study, data of consecutive advanced stage PGL patients treated with concomitant 177Lu-DOTATATE-capecitabine therapy, between July 2009 and March 2017, were collected and analyzed.ResultsTwenty-five PGL patients received an average dose of 22.86 ± 9.54 (14.43–50) GBq 177Lu-DOTATATE and 1250 mg/m2 capecitabine from days 0 to 14, commencing on the morning of PRRT. The median overall survival (OS) was not attained in this patient cohort; however, the median PFS was 32 months. Morphological response according to RECIST 1.1 criteria was achieved in 28% (7/25) patients. Biochemical response with > 50% reduction in chromogranin A levels was observed in 28% of the patients.ConclusionsOur data confirm that 177Lu-DOTATATE-capecitabine therapy is effective in achieving an objective response in 28% and symptomatic response in 43% patients. In comparison to published PRRT monotherapy outcomes in PGL, we did not observe any great advantage of concomitant therapy; however, it could be due to under-powered study. We recommend a large randomized trial to prove or disprove the utility of capecitabine as a radiosensitizer for PRRT in PGL patients.

Highlights

The role of concomitant peptide receptor radionuclide therapy (PRRT) and capecitabine therapy has shown benefit in gastroenteropancreatic neuroendocrine tumors
In 5 (20%) patients, tumor involvement was confined to the primary site, and in the remaining 20 (80%) patients, lymph node and skeletal metastases were the most common metastatic sites (Table 1)
At the time of the commencement of treatment, (PRRT-capecitabine) 21 patients presented with documented disease progression

Summary

Introduction

The role of concomitant peptide receptor radionuclide therapy (PRRT) and capecitabine therapy has shown benefit in gastroenteropancreatic neuroendocrine tumors. Data reporting its role in paraganglioma (PGL) patients is lacking. The aim of this study was to evaluate the role of combined capecitabine and 177Lu-DOTATATE in malignant PGL patients. Paragangliomas (PGLs) are catecholamine-secreting tumors with neuroendocrine (NET) characterization that arise from neural crest cells of extra-adrenal autonomic ganglia. PGLs occur in both the sympathetic and parasympathetic nervous system. The sympathetic PGLs secrete catecholamines and produce symptoms such as secondary hypertension, headache, sweating, palpitations, and anxiety [1, 2]. Studies have documented partial response, disease stabilization, and control of symptoms by improvement in the performance status with 131I-MIBG therapy [8,9,10,11,12]. The therapy is limited in patients with negative 131I-MIBG uptake on imaging. The prolonged hospital admission in the isolation room and significant hematological toxicity of 131I-MIBG therapy are limiting factors [10]

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