Thymoquinone Plus Immunotherapy in Extra-Pulmonary Neuroendocrine Carcinoma: Case Series for a Novel Combination.


Journal

Current oncology (Toronto, Ont.)
ISSN: 1718-7729
Titre abrégé: Curr Oncol
Pays: Switzerland
ID NLM: 9502503

Informations de publication

Date de publication:
21 11 2022
Historique:
received: 11 10 2022
revised: 07 11 2022
accepted: 12 11 2022
entrez: 24 11 2022
pubmed: 25 11 2022
medline: 29 11 2022
Statut: epublish

Résumé

Neuroendocrine neoplasms (NENs) are a heterogeneous group of cancers that had a significant increase in annual incidence in the last decade. They can be divided into well-differentiated neuroendocrine tumors (NETs) and poorly differentiated neuroendocrine carcinomas (NECs). Poorly differentiated NECs are aggressive forms of cancers with limited therapeutic options. The first line treatment of metastatic poorly differentiated NECs is similar to small cell lung cancer, with cytotoxic chemotherapy (etoposide plus platinum). Patients who progress have limited therapeutic options and poor overall survival, calling for other novel agents to combat this deadly disease. Therefore, in this article, we summarized the effects of a novel component, Thymoquinone (TQ, C10H12O2), which is the main bioactive component of the black seed ( We report the effect of TQ plus dual immune checkpoint inhibitors (nivolumab plus ipilimumab) in four patients with poorly differentiated gastrointestinal Ep-NEC and MiNEN who progressed on cytotoxic chemotherapy. This is the first case series to report the clinical activity of TQ plus dual immune checkpoint inhibitors (nivolumab plus ipilimumab) in patients with refractory metastatic EP-NEC. The four patients showed benefits with the combined regimen TQ plus dual ICPIs with durable response and exceeded the two years of progression-free survival. None of the four patients experienced significant toxicity, and all of them showed improvement in quality of life. The reported clinical courses suggest that combined TQ plus ICPIs is a potential promising regimen for refractory EP-NEC and MiNEN that deserves further prospective investigation.

Sections du résumé

BACKGROUND
Neuroendocrine neoplasms (NENs) are a heterogeneous group of cancers that had a significant increase in annual incidence in the last decade. They can be divided into well-differentiated neuroendocrine tumors (NETs) and poorly differentiated neuroendocrine carcinomas (NECs). Poorly differentiated NECs are aggressive forms of cancers with limited therapeutic options. The first line treatment of metastatic poorly differentiated NECs is similar to small cell lung cancer, with cytotoxic chemotherapy (etoposide plus platinum). Patients who progress have limited therapeutic options and poor overall survival, calling for other novel agents to combat this deadly disease. Therefore, in this article, we summarized the effects of a novel component, Thymoquinone (TQ, C10H12O2), which is the main bioactive component of the black seed (
METHODS
We report the effect of TQ plus dual immune checkpoint inhibitors (nivolumab plus ipilimumab) in four patients with poorly differentiated gastrointestinal Ep-NEC and MiNEN who progressed on cytotoxic chemotherapy.
RESULTS
This is the first case series to report the clinical activity of TQ plus dual immune checkpoint inhibitors (nivolumab plus ipilimumab) in patients with refractory metastatic EP-NEC. The four patients showed benefits with the combined regimen TQ plus dual ICPIs with durable response and exceeded the two years of progression-free survival. None of the four patients experienced significant toxicity, and all of them showed improvement in quality of life.
CONCLUSION
The reported clinical courses suggest that combined TQ plus ICPIs is a potential promising regimen for refractory EP-NEC and MiNEN that deserves further prospective investigation.

Identifiants

pubmed: 36421360
pii: curroncol29110707
doi: 10.3390/curroncol29110707
pmc: PMC9689659
doi:

Substances chimiques

thymoquinone O60IE26NUF
Nivolumab 31YO63LBSN
Ipilimumab 0
Immune Checkpoint Inhibitors 0

Types de publication

Case Reports

Langues

eng

Sous-ensembles de citation

IM

Pagination

9018-9030

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Auteurs

Amr Mohamed (A)

Division of Hematology and Medical Oncology, Department of Medicine, University Hospitals, Seidman Cancer Center, Case Western Reserve University, Cleveland, OH 44106, USA.

Asfar S Azmi (AS)

Division of Medical Oncology, Department of Medicine, Karmanos Cancer Institute, Wayne State University, Detroit, MI 48202, USA.

Sylvia L Asa (SL)

Seidman Cancer Center, Department of Pathology, University Hospitals, Case Western Reserve University, Cleveland, OH 44106, USA.

Sree Harsha Tirumani (SH)

Seidman Cancer Center, Department of Radiology, University Hospitals, Case Western Reserve University, Cleveland, OH 44106, USA.

Amit Mahipal (A)

Division of Hematology and Medical Oncology, Department of Medicine, University Hospitals, Seidman Cancer Center, Case Western Reserve University, Cleveland, OH 44106, USA.

Sakti Cjakrabarti (S)

Division of Hematology and Medical Oncology, Department of Medicine, University Hospitals, Seidman Cancer Center, Case Western Reserve University, Cleveland, OH 44106, USA.

David Bajor (D)

Division of Hematology and Medical Oncology, Department of Medicine, University Hospitals, Seidman Cancer Center, Case Western Reserve University, Cleveland, OH 44106, USA.

J Eva Selfridge (JE)

Division of Hematology and Medical Oncology, Department of Medicine, University Hospitals, Seidman Cancer Center, Case Western Reserve University, Cleveland, OH 44106, USA.

Ahmed O Kaseb (AO)

Division of Gastrointestinal Medical Oncology, Department of Medicine, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

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Classifications MeSH