Combined use of 177Lu-DOTATATE and metronomic capecitabine (Lu-X) in FDG-positive gastro-entero-pancreatic neuroendocrine tumors

Nicolini, Silvia; Bodei, Lisa; Bongiovanni, Alberto; Sansovini, Maddalena; Grassi, Ilaria; Ibrahim, Toni; Monti, Manuela; Caroli, Paola; Sarnelli, Anna; Diano, Danila; Iorio, Valentina Di; Grana, Chiara Maria; Cittanti, Corrado; Pieri, Federica; Severi, Stefano; Paganelli, Giovanni

doi:10.1007/s00259-021-05236-z

Cited by 34 publications

(17 citation statements)

References 32 publications

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“…This supports the rationale to use radiosensitizers to improve PRRT efficacy in a subgroup of patients identified by molecular imaging. This positive phase II study and previous results in the field [10,11] support the need for randomized comparative studies. Some clinical trials combining PRRT and the use of capecitabine, 5-fluorouracil, temozolomide, or everolimus with different schedules are growing worldwide and supportive results are expected from the Scientific Community; moreover, new therapeutic approaches are being tested in a preclinical setting [12][13][14].…”

supporting

confidence: 72%

“…The study by Nicolini et al highlights the capability of nuclear medicine imaging using both [ 18 F]FDG PET and radiolabeled somatostatin analogs imaging to drive therapeutic choices in GEP NET patients, representing a great example for stratification of patients based on molecular imaging [10]. They analyzed combined metronomic chemotherapy-PRRT treatment, using [ 177 Lu]DOTATATE, in metastatic patients with widely different pathological grading (G1-G3, Ki67 < 55%) in combination with capecitabine (pro-drug of 5-fluorouracil) [10]. Key for patient inclusion was to select subjects showing lesions with a high uptake on SSTR PET (grade 3 or 4 according to Krenning score) and at least one documented lesion positive on FDG PET (with SUV max >2.5).…”

mentioning

confidence: 99%

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Combined use of peptide receptor radionuclide therapy and metronomic chemotherapy in neuroendocrine tumors: a possible choice driven by nuclear medicine molecular imaging

Minutoli

Laudicella

Burger

et al. 2021

Eur J Nucl Med Mol Imaging

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supporting

confidence: 72%

mentioning

confidence: 99%

Combined use of peptide receptor radionuclide therapy and metronomic chemotherapy in neuroendocrine tumors: a possible choice driven by nuclear medicine molecular imaging

Minutoli

Laudicella

Burger

et al. 2021

Eur J Nucl Med Mol Imaging

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“…These are predominantly from Australia where groups have used PRCRT for over two decades, mostly using concomitant 5-fluorouracil or capecitabine [139,140]. Most recently, a phase 2 trial in 37 patients with G1-3 GEP NETs and both SSTR and FDG positive disease, indicating aggressive tumor behavior, use of 177 Lu-DOTATATE with capecitabine showed disease stability in 55% and partial response in 30% of patients over a follow-up period of 38 months, and progression-free survival of 31.4 months [141]. A randomized control trial is planned by the same study team.…”

Section: Future Directions For Prrtmentioning

confidence: 99%

Treatment of Neuroendocrine Neoplasms with Radiolabeled Peptides—Where Are We Now

Naik¹,

Al-Nahhas²,

Khan³

2022

Cancers

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Peptide receptor radionuclide therapy (PRRT) has been one of the most successful and exciting examples of theranostics in nuclear medicine in recent decades and is now firmly embedded in many treatment algorithms for unresectable or metastatic neuroendocrine neoplasms (NENs) worldwide. It is widely considered to be an effective treatment for well- or moderately differentiated neoplasms, which express high levels of somatostatin receptors that can be selectively targeted. This review article outlines the scientific basis of PRRT in treatment of NENs and describes its discovery dating back to the early 1990s. Early treatments utilizing Indium-111, a γ-emitter, showed promise in reduction in tumor size and improvement in biochemistry, but were also met with high radiation doses and myelotoxic and nephrotoxic effects. Subsequently, stable conjugation of DOTA-peptides with β-emitting radionuclides, such as Yttrium-90 and Lutetium-177, served as a breakthrough for PRRT and studies highlighted their potential in eliciting progression-free survival and quality of life benefits. This article will also elaborate on the key trials which paved the way for its approval and will discuss therapeutic considerations, such as patient selection and administration technique, to optimize its use.

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“…Toxicity was low, despite 67% of the patients having received prior chemotherapy [ 123 ]. Moreover, a prospective phase-II study was performed using a combination of 177 Lu-DOTATATE and metronomic capecitabine in 37 patients with advanced SSTR- and 18 F-FDG-positive grade 1 to 3 GEP-NETs [ 124 ]. High response rates were reported, and toxicity was acceptable.…”

Section: Optimizationmentioning

confidence: 99%

Peptide Receptor Radionuclide Therapy Targeting the Somatostatin Receptor: Basic Principles, Clinical Applications and Optimization Strategies

Bidakhvidi

Goffin

Dekervel

et al. 2021

Cancers

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Peptide receptor radionuclide therapy (PRRT) consists of the administration of a tumor-targeting radiopharmaceutical into the circulation of a patient. The radiopharmaceutical will bind to a specific peptide receptor leading to tumor-specific binding and retention. The only target that is currently used in clinical practice is the somatostatin receptor (SSTR), which is overexpressed on a range of tumor cells, including neuroendocrine tumors and neural-crest derived tumors. Academia played an important role in the development of PRRT, which has led to heterogeneous literature over the last two decades, as no standard radiopharmaceutical or regimen has been available for a long time. This review provides a summary of the treatment efficacy (e.g., response rates and symptom-relief), impact on patient outcome and toxicity profile of PRRT performed with different generations of SSTR-targeting radiopharmaceuticals, including the landmark randomized-controlled trial NETTER-1. In addition, multiple optimization strategies for PRRT are discussed, i.e., the dose–effect concept, dosimetry, combination therapies (i.e., tandem/duo PRRT, chemoPRRT, targeted molecular therapy, somatostatin analogues and radiosensitizers), new radiopharmaceuticals (i.e., SSTR-antagonists, Evans-blue containing vector molecules and alpha-emitters), administration route (intra-arterial versus intravenous) and response prediction via molecular testing or imaging. The evolution and continuous refinement of PRRT resulted in many lessons for the future development of radionuclide therapy aimed at other targets and tumor types.

show abstract

Combined use of 177Lu-DOTATATE and metronomic capecitabine (Lu-X) in FDG-positive gastro-entero-pancreatic neuroendocrine tumors

Cited by 34 publications

References 32 publications

Combined use of peptide receptor radionuclide therapy and metronomic chemotherapy in neuroendocrine tumors: a possible choice driven by nuclear medicine molecular imaging

Combined use of peptide receptor radionuclide therapy and metronomic chemotherapy in neuroendocrine tumors: a possible choice driven by nuclear medicine molecular imaging

Treatment of Neuroendocrine Neoplasms with Radiolabeled Peptides—Where Are We Now

Peptide Receptor Radionuclide Therapy Targeting the Somatostatin Receptor: Basic Principles, Clinical Applications and Optimization Strategies

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