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Peptide Receptor Radionuclide Therapy Combined With Chemotherapy in Patients With Neuroendocrine Tumors

Yordanova, Anna, MD*; Ahrens, Harriet*; Feldmann, Georg, MD; Brossart, Peter, MD; Gaertner, Florian C., MD*; Fottner, Christian, MD; Weber, Matthias M., MD; Ahmadzadehfar, Hojjat, MD, MSc*; Schreckenberger, Mathias, MD§; Miederer, Matthias, MD§; Essler, Markus, MD*

doi: 10.1097/RLU.0000000000002532
Original Articles
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Purpose Combinations of therapies may enhance therapeutic effects without significantly increasing the incidence of adverse events. However, there are few data regarding survival after concomitant chemotherapy and peptide receptor radionuclide therapy (PRRT) with [177Lu]Lu-octreotate in patients with neuroendocrine tumors (NETs). Thus, we explored the outcome of this combination of therapies.

Methods Fifteen patients with somatostatin receptor–positive, rapidly progressive G2/G3 NETs during chemotherapy or PRRT alone from 2 German cancer centers were included in the retrospective analysis. The patients received a combination of PRRT and chemotherapy with temozolomide (n = 3) or temozolomide plus capecitabine (n = 12). To evaluate the effects of the combined treatment, we assessed the responses, survival, and adverse events.

Results The cumulative administered activity of [177Lu]Lu-octreotate had a median of 21.3 GBq after 3 cycles of combination therapy. The patients exhibited a median progression-free survival of 7.1 months and a median overall survival of 25.3 months. The clinical benefit (objective response and stable disease) rates were as follows: 55% of patients according to CT, 38% in [18F]F-FDG PET/CT, and 44% in [68Ga]Ga-DOTATOC PET/CT. One patient with rapidly progressing liver metastases experienced grade 4 liver failure according to the Common Terminology Criteria for Adverse Events (version 5.0). Four other patients (27%) experienced significantly elevated (grade 3) liver parameters.

Conclusions According to different imaging modalities, the combination of PRRT and temozolomide +/− capecitabine led to disease control in 38% to 55% of the progressive NETs after PRRT or chemotherapy alone failed. The overall survival in this extensively pretreated group of patients was nearly 25 months. The majority of patients did not experience any serious adverse events.

From the Departments of *Nuclear Medicine and

Internal Medicine 3, University Hospital Bonn, Bonn;

Department of Endocrinology and Metabolism, I Medical Clinic, University Hospital, Johannes Gutenberg University of Mainz; and

§Department of Nuclear Medicine, University Medical Centre of the Johannes Gutenberg University Mainz, Mainz, Germany.

Received for publication November 25, 2018; revision accepted January 26, 2019.

Conflicts of interest and sources of funding: none declared.

Author contributions: M.E., M.M., and A.Y. contributed to the design of the study. A.Y., Ha.A., M.M., G.F., P.B., F.C.G., Ho.A., C.F., M.M.W., M.S., and M.E.: collection of data and administrative, technical, and material support. A.Y., M.M.m and M.E. drafted the manuscript. A.Y., Ha.A., and M.M. contributed to the statistical analysis. A.Y., Ha.A., M.M., G.F., P.B., F.C.G., Ho.A., C.F., M.M.W., M.S., and M.E. critically revised the manuscript.

M.M. and M.E. contributed equally and should be considered as co–last authors.

Correspondence to: Anna Yordanova, MD, Department of Nuclear Medicine, University Hospital Bonn, Sigmund-Freud-Str. 25, 53127 Bonn, Germany. E-mail: anna.yordanova@ukbonn.de.

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