First-Line Gemcitabine, Nab-Paclitaxel, and Oxaliplatin Chemotherapy With Itraconazole in Patients With Metastatic Pancreatic Cancer: A Single Institution Experience

Sawasaki, Miyuki; Taniguchi, Hiroshi; Sugihara, Ayako; Ikuta, Shinichi; Sakai, Yoshiyuki; Osaki, Yukio; Sonoda, Takashi

doi:10.21873/anticanres.16118

Cited by 4 publications

(7 citation statements)

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“…Large studies have revealed that itraconazole in combination with other current agents made cancer patients benefit from oncotherapy in laboratory and clinical trials 4,49,50 . For example, combination chemotherapy with gemcitabine, nab‐paclitaxel, oxaliplatin and itraconazole (GnPO‐ITC) regimen showed promising efficacy with manageable toxicities for controlling disease progression and improving OS in pancreatic cancer patients 51 . Through inhibiting hedgehog signaling and angiogenesis, and inducing apoptosis and autophagy and reversing multidrug drug resistance by inhibiting p‐glycoprotein, 4 itraconazole can enhance the chemotherapeutic sensitivity of other drugs and alleviate their chemotherapy resistance.…”

Section: Discussionmentioning

confidence: 99%

“… 4 , 49 , 50 For example, combination chemotherapy with gemcitabine, nab‐paclitaxel, oxaliplatin and itraconazole (GnPO‐ITC) regimen showed promising efficacy with manageable toxicities for controlling disease progression and improving OS in pancreatic cancer patients. 51 Through inhibiting hedgehog signaling and angiogenesis, and inducing apoptosis and autophagy and reversing multidrug drug resistance by inhibiting p‐glycoprotein, 4 itraconazole can enhance the chemotherapeutic sensitivity of other drugs and alleviate their chemotherapy resistance. Currently, only one recent study revealed that the combination of itraconazole and anti‐PD‐1 antibody effectively suppressed tumor growth in head and neck cancer.…”

Section: Discussionmentioning

confidence: 99%

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Itraconazole inhibits tumor growth via CEBPB‐mediated glycolysis in colorectal cancer

Zhang,

Li,

Chu

et al. 2024

Cancer Science

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Advanced colorectal cancer (CRC) is characterized by a high recurrence and metastasis rate, which is the primary cause of patient mortality. Unfortunately, effective anti‐cancer drugs for CRC are still lacking in clinical practice. We screened FDA‐approved drugs by utilizing targeted organoid sequencing data and found that the antifungal drug itraconazole had a potential therapeutic effect on CRC tumors. However, the effect and mechanism of itraconazole on CRC tumors have not been investigated. A cell line‐derived xenograft model in tumor‐bearing mice was established and single‐cell RNA sequencing was performed on tumor samples from four mice with or without itraconazole treatment. The proportion of cell populations and gene expression profiles was significantly different between the two groups. We found that itraconazole could inhibit tumor growth and glycolysis. We revealed that CEBPB was a new target for itraconazole, and that silencing CEBPB could repress CRC glycolysis and tumor growth by inhibiting ENO1 expression. Clinical analysis showed that CEBPB expression was obviously elevated in CRC patients, and was associated with poor survival. In summary, itraconazole treatment remodeled cell composition and gene expression profiles. Itraconazole inhibited cell glycolysis and tumor growth via the CEBPB–ENO1 axis. In this study, we illustrate a new energy metabolism mechanism for itraconazole on tumor growth in CRC that will provide a theoretical basis for CRC targeting/combination therapy.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Itraconazole inhibits tumor growth via CEBPB‐mediated glycolysis in colorectal cancer

Zhang,

Li,

Chu

et al. 2024

Cancer Science

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“…The choice of chemotherapy regimen was not solely determined by resectability status but also depended on the initial specialty of the treating department at our hospital, either surgery or medical oncology. For a majority of patients with borderline resectable or unresectable PDAC, the GnPO-ITC regimen, consisting of nab-paclitaxel (125 mg/m 2 ), gemcitabine (1,000 mg/m 2 ), and oxaliplatin (85 mg/m 2 ) on day 1, along with itraconazole (400 mg/day) on days -2 to +2 (UMIN-CTR: UMIN 000025398), was administered every two weeks within the medical oncology department for approximately six months [ 23 ]. In the surgical department, the gemcitabine plus S-1 regimen was predominantly used for resectable PDAC patients, typically administered over 1.5 months [ 4 ].…”

Section: Methodsmentioning

confidence: 99%

Predicting Pathological Response to Preoperative Chemotherapy in Pancreatic Ductal Adenocarcinoma Using Post-Chemotherapy Computed Tomography Radiomics

Ikuta,

Aihara,

Nakajima

et al. 2024

Cureus

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Introduction: Assessing the response to preoperative treatment in pancreatic cancer provides valuable information for guiding subsequent treatment strategies. The present study aims to develop and validate a computed tomography (CT) radiomics-based machine learning (ML) model for predicting pathological response (PR) to preoperative chemotherapy in pancreatic ductal adenocarcinoma (PDAC). Methods: Retrospective data were analyzed from 86 PDAC patients undergoing neoadjuvant or conversion chemotherapy followed by surgical resection from January 2018 to May 2023. The cohort was randomly divided into training (70%, n = 60) and testing (30%, n = 26) sets. Favorable PR was defined as Evans grade IIb or greater. Radiomic features were extracted from post-chemotherapy CT images, and dimensionality reduction was performed using the least absolute shrinkage and selection operator (LASSO) logistic regression. Four ML classifiers (Light Gradient Boosting Machine (LGBM), Random Forest, AdaBoost, and Quadratic Discriminant Analysis) were evaluated for predicting a favorable PR. Model performance was primarily assessed using the area under the receiver operating characteristic curve (AUC), Brier score, and decision curve analysis. Results: Forty-one (47.7%) patients had a favorable PR. LASSO analysis on the training set identified five radiomic features. The LGBM model demonstrated the best performance, with a training AUC of 0.902 and a testing AUC of 0.923. It also exhibited the lowest Brier scores, both in training (0.136) and testing (0.135). Decision curve analysis further confirmed its clinical potential. Conclusion: The CT radiomics-based ML model exhibited promising performance in predicting PR in PDAC after neoadjuvant/conversion chemotherapy. This suggests clinical utility in optimizing surgical candidates and timing of surgery, leading to personalized treatment strategies.

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“…Eighty-eight of the patients required second-line treatment with irinotecan. Thus, concluding that the GnPO-ITC regimen had promising results in improving OS with acceptable toxicities [ 11 ].…”

Section: Reviewmentioning

confidence: 99%

Intra-arterial Chemotherapy in Patients With Metastatic or Locally Aggressive Pancreatic Adenocarcinoma: A Scoping Review

Basra,

Patel,

Biglione

2024

Cureus

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Pancreatic adenocarcinoma refers to cancer of the pancreatic duct cells. It is normally diagnosed when it is at an advanced stage, making the prognosis poor. Systemic chemotherapy is the primary treatment approach for locally advanced or metastatic pancreatic cancer and has been shown to improve survival by eight to 16 weeks. However, it does not directly penetrate malignant tissue and has many side effects, such as hair loss, bone marrow suppression, and many gastrointestinal issues. A newer treatment modality, regional intraarterial chemotherapy (IAC), focuses on targeting malignant tissue directly to improve survival and decrease systemic side effects. When IAC is used with gemcitabine (GEM) or FLEC (5-fluorouracil, leucovorin, epirubicin, and carboplatin), the response rate for advanced pancreatic cancer is significantly improved. This literature review introduces the use of hepatic intra-arterial chemotherapy in patients with metastatic pancreatic adenocarcinoma.

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First-Line Gemcitabine, Nab-Paclitaxel, and Oxaliplatin Chemotherapy With Itraconazole in Patients With Metastatic Pancreatic Cancer: A Single Institution Experience

Cited by 4 publications

References 0 publications

Itraconazole inhibits tumor growth via CEBPB‐mediated glycolysis in colorectal cancer

Itraconazole inhibits tumor growth via CEBPB‐mediated glycolysis in colorectal cancer

Predicting Pathological Response to Preoperative Chemotherapy in Pancreatic Ductal Adenocarcinoma Using Post-Chemotherapy Computed Tomography Radiomics

Intra-arterial Chemotherapy in Patients With Metastatic or Locally Aggressive Pancreatic Adenocarcinoma: A Scoping Review

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