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1.
AME Case Rep ; 8: 42, 2024.
Article in English | MEDLINE | ID: mdl-38711889

ABSTRACT

Background: Multi-gene panel testing and advancements in molecular targeted therapy have improved the overall survival of patients with driver mutation-positive non-small cell lung cancer (NSCLC). Mesenchymal-epithelial transition factor (MET) exon 14 skipping mutation-positive NSCLC, which remains untreated with MET inhibitors, shows a poorer prognosis than do cases of NSCLC without MET mutations. However, serious treatment-related adverse events (TRAEs) act as substantial treatment barriers. Case Description: Herein, we report a case of advanced NSCLC in a male in his 40s with MET exon 14 skipping mutation. A MET-inhibitory investigational drug was administered as first-line treatment; the development of grade 3 maculopapular rash necessitated dose reduction, which resulted in disease progression. Tepotinib was then administered with dexamethasone as a third-line treatment but was discontinued owing to the re-development of the grade 3 maculopapular rash. Finally, capmatinib administration as the fifth-line treatment appeared partially effective, with no serious adverse events. The patient could successfully resume work. Conclusions: This is the first report of MET exon 14 skipping mutation-positive NSCLC wherein partial response was achieved without severe TRAEs by alternating between two MET inhibitors. If no alternative treatments are available, cautious repeated re-administration of MET inhibitors after resolving serious rashes can be considered a potential approach.

2.
Respir Med Case Rep ; 48: 102011, 2024.
Article in English | MEDLINE | ID: mdl-38510660

ABSTRACT

Inflammatory endobronchial polyps (IEPs) are rare, benign bronchial tumors posing diagnostic and therapeutic challenges owing to limited data. A 55-year-old man, receiving treatment for allergic bronchopulmonary aspergillosis, presented with a one-week history of fever and purulent sputum. Diagnosed with pneumonia, he received antimicrobial treatment. However, because of persistent symptoms, an endobronchial tumor was suspected on computed tomography. IEP was confirmed through flexible bronchoscopy with forceps biopsy, and polyp removal improved symptoms, lung function, and imaging.

3.
J Asthma ; 61(7): 663-670, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38163925

ABSTRACT

OBJECTIVE: Bronchial thermoplasty (BT) decreases the incidence of asthma exacerbations, emergency room visits, and hospitalizations among patients with severe asthma. Predictors of BT effectiveness remain unclear as its mechanism of action and invasiveness remain obscure. This study aimed to identify factors that could predict BT outcomes. METHODS: Two respiratory physicians treated 20 consecutive patients with severe asthma using BT. The patients were assigned to groups based on clinical remission following an expert consensus proposed in 2020. Predictors of clinical remission were analyzed using asthma control test (ACT) score, pulmonary function and blood tests, and fractional exhaled nitric oxide. RESULTS: At baseline, the median age was 44 years (interquartile range [IQR], 31.0-52.8), and pre-bronchodilator (pre-BD) percent predicted forced expiratory volume in one second (%FEV1) was 85.9% (IQR, 74.8-100.5). Six (30%) patients achieved clinical remission. Among the patients treated with biologics, 20% had clinical remission, and 20% discontinued biologic therapy. The pre-BT ACT score was significantly lower in the group with than without remission (11.0 [IQR, 8.0-14.5] vs. 15.0 [IQR, 11.0-17.3], p = .016). Adverse events did not significantly differ between the groups. CONCLUSIONS: To the best of our knowledge, this is the first study to use clinical remission as a criterion for evaluating BT efficacy. The pre-BT ACT score might a the predict response to BT in younger adult patients with severe asthma and pre-BD %FEV1 ≥ 70%.


Subject(s)
Asthma , Bronchial Thermoplasty , Respiratory Function Tests , Humans , Asthma/therapy , Asthma/physiopathology , Male , Adult , Female , Bronchial Thermoplasty/methods , Middle Aged , Severity of Illness Index , Remission Induction , Forced Expiratory Volume , Treatment Outcome , Lung/physiopathology
4.
Clin Lung Cancer ; 25(1): e52-e57.e2, 2024 01.
Article in English | MEDLINE | ID: mdl-37932180

ABSTRACT

BACKGROUND: In patients with epidermal growth factor receptor (EGFR) mutated non-small-cell lung cancer (NSCLC), EGFR-tyrosine kinase inhibitor (TKI) interruption due to EGFR-TKI-induced interstitial lung disease (ILD) is a factor for shorter overall survival (OS). Several retrospective cohort studies have reported an OS-prolonging effect of the readministration of EGFR-TKIs. This study aimed to determine the safety of readministration of EGFR-TKIs after the onset of EGFR-TKI-induced ILD. METHODS: The PubMed, CINAHL, and Web of Science databases were systematically searched until May 30, 2023. The primary outcome was successful readministration of EGFR-TKIs after the onset of EGFR-TKI-induced ILD. RESULTS: A total of 690 patients were included in this meta-analysis. The initial EGFR-TKI-induced ILD rate was 13.6% (95% confidence interval [CI]:6.4-20.9). Readministration rate of EGFR-TKI after onset of EGFR-TKI-induced ILD was 40.2% (95% CI: 26.7-53.7). The successful readministration rate of EGFR-TKIs after onset of EGFR-TKI-induced ILD was 81.9% (95% CI: 73.8-90.0). Successful rate of EGFR-TKI readministration in patients with Grade 2 or higher adverse events post initial EGFR-TKI therapy was 76.1% (95% CI: 55.6-96.6). CONCLUSIONS: Although initial EGFR-TKI-induced ILD has a relatively high incidence, EGFR-TKI readministration after the onset of EGFR-TKI-induced ILD may be a viable treatment option.


Subject(s)
Antineoplastic Agents , Carcinoma, Non-Small-Cell Lung , Lung Diseases, Interstitial , Lung Neoplasms , Humans , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/genetics , Lung Neoplasms/drug therapy , Lung Neoplasms/genetics , Lung Neoplasms/chemically induced , Antineoplastic Agents/adverse effects , Retrospective Studies , Protein Kinase Inhibitors/adverse effects , ErbB Receptors , Lung Diseases, Interstitial/chemically induced , Mutation/genetics
5.
Mol Clin Oncol ; 17(3): 139, 2022 Sep.
Article in English | MEDLINE | ID: mdl-35949896

ABSTRACT

Bevacizumab is a humanized monoclonal antibody that contains <10% murine protein. To prevent infusion-related hypersensitivity reactions (HSRs), the initial bevacizumab infusion is delivered for 90 min, the second for 60 min and subsequent doses for 30 min. Several previous studies have shown that short bevacizumab infusions are safe and do not result in severe HSRs in patients with colorectal, lung, ovarian and brain cancer. However, the efficacy of short bevacizumab infusions for colorectal cancer management remains unclear. Therefore, to investigate this issue, a prospective multicenter study was conducted using 23 patients enrolled between June 2017 and March 2019. The initial infusion of bevacizumab was for 30 min followed by a second infusion rate of 0.5 mg/kg/min (5 mg/kg over 10 min and 7.5 mg/kg over 15 min. The primary endpoint was progression-free survival (PFS). The overall response and disease control rates were 57 and 87%, respectively. The median PFS time was 306 days (interquartile range, 204-743 days). No HSRs were noted. Adverse events associated with bevacizumab included grade 4 small intestinal perforation and grade 3 stroke in 1 patient each. These results suggest that a short bevacizumab infusion regime comprising an initial infusion for 30 min followed by a second infusion at 0.5 mg/kg/min is safe and efficacious for the management of colorectal cancer.

6.
Life (Basel) ; 11(8)2021 Aug 06.
Article in English | MEDLINE | ID: mdl-34440540

ABSTRACT

Next-generation sequencing-based comprehensive genome profiling (CGP) testing, OncoGuide NCC Oncopanel System, and FoundationOne CDx Cancer Genomic Profile have been covered by the Japanese national health insurance system since June 2019. Because CGP was initially developed to enroll patients into an early-phase clinical trial for solid tumors, its approved indications have been limited to patients who have completed the standard chemotherapy treatment. Approximately 14,000 cases have been registered with the Center for Cancer Genomics and Advanced Therapeutics as of March 2021. Measuring the drug access rate is not enough due to patients' deteriorating condition during CGP analysis and due to the limited number of ongoing clinical trials available, although tumor-agnostic therapies, such as the use of pembrolizumab in high microsatellite-instable solid tumors and in conditions with a high tumor mutational burden (≥10 mut/Mb) as well as the use of entrectinib and larotrectinib in NTRK fusion-positive tumors have been approved in Japan. Moreover, since this analysis is performed using DNA derived from tumor tissue, it is difficult to perform CGP in cases in which an insufficient amount of tissue exists. Thus, noninvasive blood-based assays have been developed, and CGP panels using circulating tumor DNA from blood were approved in March 2021. However, cost, timing, and the number of tests allowed by the health system have not yet been determined. Therefore, in this review, we outline the current status and issues of CGP testing using tumor tissues as well as the expectations and limitations of liquid biopsy for use in Japanese clinical practice.

7.
Gastric Cancer ; 21(3): 439-445, 2018 May.
Article in English | MEDLINE | ID: mdl-28766263

ABSTRACT

BACKGROUND: A combination of S-1 and cisplatin is recognized as one of the standard first-line chemotherapy regimens for patients with advanced gastric cancer. However, demographic analyses of pivotal phase III studies have showed that only a minority of treated patients were aged 76 years or older. The purpose of this phase II study was to evaluate the safety and efficacy of combination therapy with S-1 and cisplatin in elderly patients with chemotherapy-naive advanced gastric cancer. METHODS: Patients aged 76 years or older received S-1 40 mg/m2 orally twice daily for 21 days and cisplatin 60 mg/m2 intravenously infused at day 8 of each 35-day cycle. Dose modification was performed according to creatinine clearance. The primary endpoint was overall survival (OS). Secondary endpoints included response rate, progression-free survival (PFS), time to treatment failure (TTF), and adverse events. RESULTS: A total of 40 patients were enrolled. Median OS was 12.3 months, PFS was 7.8 months, and TTF was 4.3 months. The response rate was 54%. The most common grade 3-4 adverse events were anorexia (25%), neutropenia (23%), hyponatremia (20%), anemia (18%), and febrile neutropenia (8%). No treatment-related death occurred. CONCLUSIONS: Combination chemotherapy with S-1 and cisplatin is an effective and well-tolerated regimen for elderly patients with advanced gastric cancer when the dose is adjusted according to renal function.


Subject(s)
Adenocarcinoma/drug therapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Stomach Neoplasms/drug therapy , Adenocarcinoma/mortality , Administration, Oral , Aged , Aged, 80 and over , Cisplatin/administration & dosage , Cisplatin/adverse effects , Disease-Free Survival , Drug Combinations , Female , Humans , Kaplan-Meier Estimate , Male , Oxonic Acid/administration & dosage , Oxonic Acid/adverse effects , Stomach Neoplasms/mortality , Tegafur/administration & dosage , Tegafur/adverse effects , Treatment Outcome
8.
Gastric Cancer ; 16(1): 41-7, 2013 Jan.
Article in English | MEDLINE | ID: mdl-22311679

ABSTRACT

BACKGROUND: Regimens of standard-dose cisplatin have usually been administered as inpatient chemotherapy in Japan. This prospective study evaluated the feasibility of outpatient chemotherapy with standard-dose cisplatin in Japanese patients with advanced gastric cancer. METHODS: Advanced gastric cancer patients received an S-1 + cisplatin regimen (S-1: 80-120 mg days 1-21; cisplatin: 60 mg/m(2) day 8, every 4-5 weeks), either as outpatient chemotherapy with oral hydration on days 9-10, or as inpatient chemotherapy with intravenous hydration on days 9-10, based on the results of an oral hydration test during days 1-7 of the first cycle. The primary endpoint was the completion rate of two cycles in the outpatient group. RESULTS: A total of 36 patients were enrolled: 32 were allocated to the outpatient group and 4 to the inpatient group. The completion rate of two cycles in the outpatient group was 78% [90% confidence interval (CI): 63-89]. The median of the total number of treatment cycles of S-1 + cisplatin and the median progression-free survival in the outpatient group were 5 (range 1-11) and 10.6 months (95% CI 4.2-16.9), respectively. Although seven patients in the outpatient group discontinued treatment, mainly owing to gastrointestinal toxicity, most of them could continue S-1 + cisplatin by switching to inpatient chemotherapy from the next cycle. CONCLUSION: Outpatient chemotherapy with S-1 + cisplatin in advanced gastric cancer patients can be safely and effectively administered in Japan with appropriate patient selection and supportive treatment.


Subject(s)
Ambulatory Care/methods , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Stomach Neoplasms/drug therapy , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Cisplatin/administration & dosage , Disease-Free Survival , Drug Combinations , Feasibility Studies , Female , Humans , Japan , Male , Middle Aged , Oxonic Acid/administration & dosage , Patient Selection , Prospective Studies , Stomach Neoplasms/pathology , Tegafur/administration & dosage , Treatment Outcome
9.
Gan To Kagaku Ryoho ; 39(3): 389-93, 2012 Mar.
Article in Japanese | MEDLINE | ID: mdl-22421765

ABSTRACT

Capecitabine(Xeloda®)has been a global standard drug for the treatment of colon cancer since large randomized controlled trials demonstrated its efficacy and safety in treating patients suffering from the disease. Few studies have been conducted to assess the effects of oral capecitabine treatment on Japanese patients. Therefore, we conducted this study to evaluate oral capecitabine as postoperative adjuvant chemotherapy in 50 patients who underwent surgery for stage III colon cancer at our department. Patients received an 8 courses treatment with capecitabine during the study, and the incidence of adverse events, treatment completion rate, and treatment compliance were assessed. Adverse events were reported in a total of 46 patients(92%). The most common adverse event was hand foot syndrome(HFS), reported in 39 patients(78%), whereas bone-marrow toxicity and diarrhea were reported in as few as 2(4%)and 3(6%)patients, respectively. Both these events were mild in severity, and no patients required hospitalization, nor were they associated with treatment-related deaths. The median treatment duration was 8 courses ranging from 3 to 8 courses, and the 8 courses treatment completion rate was 96%. The relative dose intensity, which was used as a treatment compliance index, is expressed as the actual dose taken by the patient divided by the dose planned at baseline. The median and mean of the relative dose intensity were 100%(ranging from 37% to 100%)and 93%, respectively. The results of this study showed that the safety profile of oral capecitabine therapy was generally favorable, with a lower incidence and lesser severity of life-threatening bone-marrow toxicity and diarrhea, although the treatment is still associated with frequent HFS. This is the great advantage of capecitabine when it is used as postoperative adjuvant chemotherapy for gastrointestinal cancer. Indeed, a satisfactory treatment completion rate was achieved in this study while maintaining a sufficient dose and treating HFS, by reducing the dose, interrupting treatment, or providing appropriate corrective measures.


Subject(s)
Antimetabolites, Antineoplastic/therapeutic use , Colonic Neoplasms/drug therapy , Deoxycytidine/analogs & derivatives , Fluorouracil/analogs & derivatives , Administration, Oral , Adult , Aged , Aged, 80 and over , Antimetabolites, Antineoplastic/administration & dosage , Antimetabolites, Antineoplastic/adverse effects , Capecitabine , Chemotherapy, Adjuvant , Colonic Neoplasms/pathology , Colonic Neoplasms/surgery , Deoxycytidine/administration & dosage , Deoxycytidine/adverse effects , Deoxycytidine/therapeutic use , Female , Fluorouracil/administration & dosage , Fluorouracil/adverse effects , Fluorouracil/therapeutic use , Hand-Foot Syndrome , Humans , Male , Middle Aged , Neoplasm Staging
10.
J Cancer Res Clin Oncol ; 136(7): 1059-64, 2010 Jul.
Article in English | MEDLINE | ID: mdl-20037789

ABSTRACT

PURPOSE: First-line chemotherapy (Cx-1) in advanced gastric cancer (AGC) provides survival benefit. However, it is unclear who should proceed to second-line chemotherapy (Cx-2). METHODS: We reviewed patients who received Cx-2 for AGC following progressive disease after Cx-1 from 2000 to 2005 at the National Cancer Center Hospital, Tokyo. To evaluate the prognostic factors in Cx-2, Cox regression multivariate analysis was performed. RESULTS: Of 995 patients who received Cx-1 in this study period, 466 met the eligibility criteria. The median progression-free survival in Cx-1 (PFS-1) was 133 days. The median survival time from the date of starting second-line chemotherapy (MST-2) was 207 days. Multivariate analysis revealed that the factors affecting short survival time in Cx-2 were poor performance status (> or = 2), low serum albumin level (<3.5 mg/dL), elevated C-reactive protein level (> or = 1.0 mg/dL), patients with bone, liver or peritoneal metastasis, and patients without previous gastrectomy (p < 0.01). PFS-1 was an independent prognostic factor for survival (PFS-1 <120, MST-2 133 days, PFS-1 > or = 120, MST-2 258 days, hazard ratio 0.71, 95% confidence interval 0.58-0.86, p < 0.01). The Cx-2 regimen (irinotecan vs. taxane) did not correlate with survival. CONCLUSION: PFS-1 is one of the prognostic factors of Cx-2 in patients with AGC.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Stomach Neoplasms/diagnosis , Stomach Neoplasms/drug therapy , Adult , Aged , Disease-Free Survival , Female , Humans , Male , Middle Aged , Multivariate Analysis , Prognosis , Risk Factors , Stomach Neoplasms/pathology , Young Adult
11.
Sangyo Eiseigaku Zasshi ; 47(1): 33-9, 2005 Jan.
Article in Japanese | MEDLINE | ID: mdl-15742612

ABSTRACT

In 1992, Brugada et al. reported a characteristic electrocardiogram (ECG) pattern and ST-segment elevation in leads V1 to V3 associated with sudden death in patients without demonstrable structural heart disease. That disease is now called Brugada Syndrome. The diagnostic criteria for the Brugada Syndrome have still not been decided on, and the prevalence of Brugada type ECG (B-ECG) varies widely in Japan. Therefore, we should consider B-ECG according to the consensus statement from the European Society of Cardiology and we proposed its management in health examinations. There were 35 B-ECG cases (0.9%), all male out of 3,875 Postal Service Trainees. There were 5 cases of Type I (Coved) (0.13%), 21 cases of Type II (0.54%), and 9 cases of Type III (0.23%), Only one case (0.026%) of Brugada Syndrome was found, and eventually, he received an Implantable Cardioverter Defibrillator (ICD). Type I (Coved) may be a more important electrocardiographic factor having a stronger causal relation to Ventricular Arrhythmia. Therefore, in management of health examinations, Type I patients with syncope or a family history of sudden cardiac death should visit a cardiologist for ICD-implantation, and even without any cardiac symptoms (syncope and a family history of sudden death), they are advised to visit a cardiologist for a program electrical stimulation (PES). Type II and III patients with any cardiac symptoms are advised to visit a cardiologist for PES or a drug challenge.


Subject(s)
Death, Sudden, Cardiac/prevention & control , Electrocardiography/classification , Long QT Syndrome/diagnosis , Tachycardia, Ventricular/diagnosis , Ventricular Fibrillation/diagnosis , Adult , Death, Sudden, Cardiac/etiology , Defibrillators, Implantable , Female , Humans , Long QT Syndrome/therapy , Male , Middle Aged , Occupational Health , Physical Examination , Reference Standards , Referral and Consultation , Syndrome , Tachycardia, Ventricular/therapy , Ventricular Fibrillation/therapy
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