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2.
In Vivo ; 37(2): 747-755, 2023.
Article in English | MEDLINE | ID: mdl-36881083

ABSTRACT

BACKGROUND/AIM: The advent of immune checkpoint inhibitor (ICI) treatment has transformed the treatment of recurrent or metastatic head and neck cancer; however, nasopharyngeal carcinoma (NPC) has not been included in major phase III trials. The clinical outcomes of ICI for NPC in real-world practice remain to be fully elucidated. PATIENTS AND METHODS: We retrospectively reviewed 23 patients with recurrent or metastatic NPC treated with nivolumab or pembrolizumab at 6 institutions from April 2017 to July 2021 and investigated the correlation of clinicopathological factors and immune-related adverse events with the effects of ICI therapy and the prognosis. RESULTS: The objective response rate was 39.1% and the disease control rate was 78.3%. The median progression-free survival was 16.8 months and overall survival has not been reached. As with other treatment procedures, the efficacy and the prognosis tended to be better in EBER-positive cases than in EBER-negative cases. The rate of significant immune-related adverse events that necessitated discontinuation of treatment was only 4.3%. CONCLUSION: ICI monotherapy (e.g., nivolumab and pembrolizumab) was effective and tolerable for NPC in a real-world setting.


Subject(s)
Immune Checkpoint Inhibitors , Nasopharyngeal Neoplasms , Humans , Immune Checkpoint Inhibitors/adverse effects , Nivolumab/adverse effects , Japan , Nasopharyngeal Carcinoma/drug therapy , Retrospective Studies , Nasopharyngeal Neoplasms/drug therapy
3.
Anticancer Res ; 42(7): 3653-3664, 2022 Jul.
Article in English | MEDLINE | ID: mdl-35790253

ABSTRACT

BACKGROUND/AIM: This study investigated the effectiveness of pembrolizumab with or without chemotherapy on advanced-stage head and neck cancer (HNC), including nasopharyngeal, sinonasal cavity and external auditory canal cancer, in a real-world setting. PATIENTS AND METHODS: We retrospectively collected data from 97 HNC patients who were treated with pembrolizumab alone (n=60) or with chemotherapy (n=37), and we investigated the association between clinicopathological findings and treatment response or prognosis. RESULTS: Patients treated with pembrolizumab and chemotherapy had a 1-year overall survival (OS) of 72.8%, objective response rate (ORR) of 48.6%, and serious (≥G3) adverse events (AEs) of 29.7%. Patients treated with pembrolizumab alone had a 1-year OS of 51.9%, ORR of 21.7%, and ≥G3 AEs of 6.7%. Both the ORR and disease control rate (DCR) in the pembrolizumab with chemotherapy group were significantly better than those in the pembrolizumab group (p=0.074 and p=0.00101, respectively). Among patients with distant metastasis, patients on pembrolizumab with chemotherapy achieved significantly better OS than pembrolizumab alone (p=0.0039). Among patients in the pembrolizumab group, both AE-positive and better performance status were associated with longer OS (p=0.011 and p=0.0037, respectively). CONCLUSION: Our real-world experience reinforces the durability and effectiveness of pembrolizumab for HNC patients. Additionally, our results suggest that pembrolizumab with chemotherapy might be recommended for patients with distant metastasis and no prior treatment. Further studies are needed to determine the optimal treatment strategy for HNC.


Subject(s)
Antineoplastic Agents, Immunological , Head and Neck Neoplasms , Lung Neoplasms , Antibodies, Monoclonal, Humanized , Antineoplastic Agents, Immunological/adverse effects , Head and Neck Neoplasms/drug therapy , Humans , Lung Neoplasms/pathology , Retrospective Studies
4.
PLoS One ; 17(7): e0271907, 2022.
Article in English | MEDLINE | ID: mdl-35901098

ABSTRACT

OBJECTIVES: The benefit of sequential therapy after immune checkpoint inhibitor (ICI) treatment for recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) has been recently reported. Furthermore, there is a growing interest in the impact of cetuximab (Cmab)-containing salvage chemotherapy (SCT) and the therapeutic efficacy and adverse events (AEs) of Cmab administration prior to ICI administration. MATERIALS AND METHODS: We retrospectively reviewed the medical records of 52 patients with R/M HNSCC treated with SCT (weekly paclitaxel [PTX], n = 7, or weekly PTX and Cmab [PC], n = 45). RESULTS: The objective response rate (ORR) and a disease control rate (DCR) was 53.3% and 91.1% in the PC group and 42.9% and 57.1% in the PTX group, respectively. There was a significant difference in the DCR between the PC and PTX groups (p = 0.0143). The overall survival (OS) and progression-free survival were significantly better in the PC group than in the PTX group. On the other hand, the incidence of drug-induced interstitial pneumonia (DI-IP) in R/M HNSCC patients who received SCT was 21.2%. Patients in the PC group were divided according to whether they received Cmab (Group A) or did not receive Cmab (Group B) as palliative therapy prior to ICIs. Group B had a significantly better OS than Group A. Furthermore, our findings suggest that the incidence rate of DI-IP during SCT might be higher in Group B. CONCLUSION: Although PC following ICIs shows dramatic efficacy, careful monitoring of AEs, including DI-IP, is recommended.


Subject(s)
Cetuximab , Head and Neck Neoplasms , Immune Checkpoint Inhibitors , Paclitaxel , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Cetuximab/adverse effects , Head and Neck Neoplasms/drug therapy , Head and Neck Neoplasms/etiology , Humans , Neoplasm Recurrence, Local/pathology , Paclitaxel/adverse effects , Retrospective Studies , Squamous Cell Carcinoma of Head and Neck/drug therapy , Squamous Cell Carcinoma of Head and Neck/etiology
5.
In Vivo ; 36(2): 979-984, 2022.
Article in English | MEDLINE | ID: mdl-35241559

ABSTRACT

BACKGROUND/AIM: Surgery remains the standard treatment for salivary gland carcinoma (SGC). Our study investigated the association between epidermal growth factor receptor (EGFR) status in recurrent/metastatic SGC and the effectiveness of treatment with cisplatin/carboplatin and 5-fluorouracil plus cetuximab (EXTREME). PATIENTS AND METHODS: We retrospectively collected 19 SGCs from patients treated with the EXTREME regimen. After analyzing EGFR expression and gene copy number gain, we evaluated the correlation between EGFR status and clinicopathological factors and prognosis. RESULTS: EGFR overexpression was detected in 77.8% cases, but not statistically associated with clinicopathological factors or prognosis. EGFR gene copy number gain was detected in 16.7% cases, and statistically positively correlated with lymph node metastasis (p=0.0291). The best overall response was partial response in two cases, stable disease in 15, and progressive disease in one case. The EXTREME regimen was discontinued in all cases. CONCLUSION: Our results suggest that SGCs are positive for EGFR protein expression but the response rate to the EXTREME regimen was unremarkable.


Subject(s)
Cisplatin , Salivary Gland Neoplasms , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Carboplatin/adverse effects , Cetuximab/adverse effects , Cisplatin/therapeutic use , Fluorouracil , Humans , Neoplasm Recurrence, Local/pathology , Retrospective Studies
6.
Anticancer Res ; 42(2): 981-989, 2022 Feb.
Article in English | MEDLINE | ID: mdl-35093898

ABSTRACT

BACKGROUND/AIM: The efficacy of programmed cell death 1 (PD-1) inhibitor therapy for patients with recurrent and/or metastatic salivary gland carcinoma (R/M SGC) remains unclear. PATIENTS AND METHODS: We retrospectively analyzed 36 patients with R/M SGC treated with PD-1 inhibitor. The expression of programmed cell death ligand 1 (PD-L1) and mismatch repair (MMR) proteins was also analyzed. RESULTS: The objective response rate (ORR) was 11.1%. The histopathological subtypes of patients who achieved complete response or partial response were salivary duct carcinoma (SDC) in three patients and poorly differentiated carcinoma in one patient, all of whom showed a positive PD-L1 expression. The expression of MMR proteins was not associated with the efficacy of PD-1 inhibitors. CONCLUSION: Although the efficacy of PD-1 inhibitor therapy in R/M SGC is limited, certain patients may respond and achieve long-term disease control. There is a potential therapeutic effect in SDC patients with positive PD-L1 expression.


Subject(s)
Carcinoma/drug therapy , Immune Checkpoint Inhibitors/therapeutic use , Salivary Gland Neoplasms/drug therapy , Adult , Aged , Aged, 80 and over , B7-H1 Antigen/metabolism , Carcinoma/metabolism , Carcinoma/mortality , Carcinoma/pathology , Female , Humans , Male , Middle Aged , Retrospective Studies , Salivary Gland Neoplasms/metabolism , Salivary Gland Neoplasms/mortality , Salivary Gland Neoplasms/pathology , Survival Analysis , Treatment Outcome
7.
Acta Otolaryngol ; 140(12): 1043-1048, 2020 Dec.
Article in English | MEDLINE | ID: mdl-32808841

ABSTRACT

BACKGROUND: Significant immune-related adverse events (irAEs) requiring therapy discontinuation sometimes occur. The influence of discontinuation on disease control after an irAE is unclear. OBJECTIVES: The aim of this study was to investigate whether or not patients continued to show a response or durable disease control even after stopping therapy following an irAE. MATERIAL AND METHODS: The response after nivolumab monotherapy discontinuation was examined for 14 patients in whom therapy was stopped without progression. RESULTS: The best response was CR in 5 (36%) patients, PR in 8 (57%) patients and SD in 1 (7%) patient. The estimated 1-year overall and progression-free survival rates were 92.9% and 78.6%, respectively. The best response during nivolumab therapy in patients who developed PD was CR in 0 of 5 patients (0%), PR in 3 of 8 patients (38%) and SD in 1 patient (100%). Patients obtaining CR tended to have a lower risk of PD than those with PR or SD. CONCLUSIONS AND SIGNIFICANCE: Patients with CR status may continue to show a response or durable disease control even after stopping therapy due to an irAE.


Subject(s)
Antineoplastic Agents, Immunological/adverse effects , Head and Neck Neoplasms/drug therapy , Nivolumab/adverse effects , Aged , Aged, 80 and over , Antineoplastic Agents, Immunological/therapeutic use , Disease Progression , Female , Head and Neck Neoplasms/mortality , Head and Neck Neoplasms/pathology , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Neoplasm Metastasis , Neoplasm Recurrence, Local , Nivolumab/therapeutic use , Remission Induction , Treatment Outcome
8.
Cancers (Basel) ; 12(8)2020 Aug 15.
Article in English | MEDLINE | ID: mdl-32824226

ABSTRACT

Recent studies have suggested the benefit of salvage chemotherapy (SCT) after immune checkpoint inhibitor (ICI) treatment for recurrent and metastatic head and neck squamous cell carcinoma (R/M HNSCC). We retrospectively examined the outcome of SCT and the usefulness of the serum C-reactive protein level (CRP) and neutrophil-to-lymphocyte ratio (NLR) as prognostic biomarkers. Thirty-nine patients with R/M HNSCC were enrolled in this study. Twenty-five patients (64.1%) received combination chemotherapy of weekly paclitaxel and cetuximab (PC) as SCT, and 14 patients (35.9%) received tegafur-gimestat-otastat potassium (S1), an oral fluoropyrimidine. In all patients, the response rate, disease control rate, median progression-free survival (PFS), and median overall survival (OS) were 45.2%, 85.7%, 6.5 months, and 13.5 months, respectively. No chemotherapy-related deaths were observed. These PC groups had low CRP (<1.2 mg/dL) or low NLR (<7.0) values at the time of SCT induction, which was significantly associated with an improved OS (p = 0.0440, p = 0.0354). A multivariate analysis also showed that a lower CRP value was significantly associated with a better OS (p = 0.0078). We clarified the usefulness of the PC and S1 regimens as SCT. In addition, SCT with the PC regimen showed a better prognosis with a lower CRP or NLR at induction than a higher CRP or NLR. This is the first report on biomarkers of SCT in R/M HNSCC.

9.
World Neurosurg ; 140: 332-337, 2020 08.
Article in English | MEDLINE | ID: mdl-32473330

ABSTRACT

BACKGROUND: Salivary duct carcinoma (SDC) is a rare parotid tumor that often develops as a rapidly growing mass with a poor prognosis. It has a high rate of distant metastases, sometimes with infiltration along nerves. We describe a case of SDC that originated outside the cranium and extended into the cranium along the path of the facial nerve. CASE DESCRIPTION: A 74-year-old man underwent magnetic resonance imaging at a local hospital, which revealed a tumor in the left internal acoustic canal; the patient was referred to our department. A left facial schwannoma was suspected, and magnetic resonance imaging was performed again 6 months later. Rapid tumor growth was confirmed, and the tumor was resected. The tumor displayed atypical epithelial cells with comedo necrosis and cribriform structure and was diagnosed as SDC. All residual intracranial tumors were removed using the middle fossa approach. The tumor, which was considered to be a primary tumor, was found near the stylomastoid foramen, and it was removed with the parotid gland. Five months after the initial surgery, metastasis to the trigeminal nerve was observed, and this was removed using a retrosigmoid approach, followed by radiation therapy. CONCLUSIONS: All 4 surgical specimens of this case were presented, and the path of tumor progression was examined in detail. Although the primary lesion was small, intracranial invasion along the facial nerve occurred. SDC should be considered as a tumor that can extend into the cranium, even with a small primary lesion.


Subject(s)
Facial Nerve/pathology , Neoplasm Invasiveness/pathology , Salivary Ducts/pathology , Salivary Gland Neoplasms/pathology , Aged , Facial Nerve/diagnostic imaging , Facial Nerve/surgery , Humans , Magnetic Resonance Imaging , Male , Neoplasm Invasiveness/diagnostic imaging , Neurosurgical Procedures , Salivary Ducts/diagnostic imaging , Salivary Ducts/surgery , Salivary Gland Neoplasms/diagnostic imaging , Salivary Gland Neoplasms/surgery , Treatment Outcome
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