Summary
Thymic carcinoma is a very rare neoplasm for which no optimal chemotherapeutic regimen has been established to date. Hence, we performed this study to investigate the efficacy and safety of ...carboplatin plus nanoparticle albumin-bound (
nab
)-paclitaxel as a first-line regimen for patients with advanced thymic carcinoma. We conducted this multi-institutional retrospective cohort study of patients with advanced thymic carcinoma who had received carboplatin plus
nab
-paclitaxel as a first-line chemotherapy between August 2013 and December 2021. Twelve patients were included in this study and were subjected to efficacy and safety analysis. Their median age was 62 years (range, 47–74 years), and all had an Eastern Cooperative Oncology Group performance status score of 0 or 1. After a median follow-up time of 19.7 months, the overall response rate was 50%; the median progression-free and overall survival times were 8.8 months and 23.3 months, respectively. Chemotherapy-related peripheral neuropathy was observed in 2 patients (16%; each with grade 1). Other toxicities were manageable, and there were no treatment-related deaths. Carboplatin plus
nab
-paclitaxel as a first-line chemotherapy regimen showed good efficacy and safety in patients with advanced thymic carcinoma.
The efficacy of combined modality therapy is evaluated for patients with extensive-stage (ES) small cell lung cancer (SCLC). This study evaluated prognostic factors affecting the risk of thoracic ...progression in ES-SCLC patients likely to undergo thoracic radiotherapy combined chemotherapy.
A retrospective review of ES-SCLC patients who had received systemic chemotherapy at our hospital was performed. Tumor size, metastatic sites, and laboratory data at diagnosis were evaluated as potential prognostic factors. In ES-SCLC patients without pleural dissemination, the rate of thoracic progression after initial chemotherapy was assessed.
Eighty-three of 96 consecutive ES-SCLC patients were analyzed. The overall response rate was 55 %, median progression free survival was 5.0 months (mo), and overall survival (OS) was 9.2 mo. Tumor size (19.4 mo for ≤3 cm vs. 8.5 mo for >3 cm, p = 0.017) and the number of metastatic sites (12.9 mo for single sites vs. 7.1 mo for multiple sites, p = 0.015) were prognostic factors, in addition to known prognostic factors such as performance status and the levels of LDH and sodium. Cox proportional hazard model showed that the OS was significantly worse in patients with large (>3 cm) primary tumor size {HR 2.44 95 % confidential interval (CI) 1.05-5.68, p = 0.038} and multiple metastatic sites HR 1.81 (95 % CI 1.08-3.04), p = 0.026. In 51 cases without pleural dissemination, the number of metastatic sites was associated with thoracic progression after initial chemotherapy (65 % for single sites vs. 36 % for multiple sites, p = 0.036).
Large tumor size and multiple metastatic sites at diagnosis significantly predicted poor survival in ES-SCLC patients. Based on the high rate of thoracic progression in ES-SCLC patients with single site of distant metastasis, we should consider thoracic radiotherapy combined with chemotherapy for this population.
The data of sequential therapy of anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) in clinical practice have been limited.
We reviewed the clinical data of patients with ...ALK-rearranged non-small cell lung cancer who received crizotinib (CRZ) or alectinib (ALEC) between May 2012 and December 2016. Patients were divided into two groups based on the first-administered ALK-TKI, the CRZ or ALEC group. The combined time-to-treatment failure (TTF) was defined as the sum of the ‘TTF of CRZ’ plus the ‘TTF of ALEC’ if patients were treated with CRZ followed by ALEC in the CRZ group. The primary end-point is the comparison between the combined TTF and the TTF of ALEC in the ALEC group.
Of 864 patients enrolled from 61 institutions, 840 patients were analysed. There were 535 of 305 patients in the CRZ/ALEC groups. The combined TTF in the CRZ group was significantly longer than TTF in the ALEC group (median, 34.4 versus 27.2 months; hazard ratio HR, 0.709; P = 0.0044). However, there was no significant difference in overall survival (OS) between the patients who received ALEC after CRZ in the CRZ group and the patients in the ALEC group (median, 88.4 months versus. not reached; HR, 1.048; P = 0.7770). In the whole population, the CRZ group had a significantly shorter OS than the ALEC group (median, 53.6 months versus not reached; HR, 1.821, P < 0.0001).
The combined TTF in the CRZ group was significantly longer than the TTF in the ALEC group; however, OS benefit of sequential therapy against ALEC as the first ALK-TKI was not shown.
•Large-scale real-world data showed longer progression-free survival of alectinib than crizotinib.•But, propensity score analysis of overall survival could not show the superiority of alectinib.•Poor responders to crizotinib had poorer response also to alectinib.•Ceritinib or lorlatinib showed activity even after crizotinib or alectinib therapy.•Meanwhile, immunotherapy could not show clinical benefit in our data.
This study aimed to examine the prognostic impact of concomitant pH-regulating drug use in patients with epidermal growth factor receptor (EGFR)-mutation-positive non-small-cell lung cancer (NSCLC) ...receiving EGFR-tyrosine kinase inhibitors (TKIs).
We conducted a nationwide retrospective cohort study and reviewed clinical data of consecutive patients with NSCLC treated with the first-line EGFR-TKIs in 46 hospitals between April 2010 and March 2020. Cox regression analyses were conducted to examine the differences in overall survival (OS) between patients treated with and without concomitant pH-regulating drugs, including potassium-competitive acid blockers (P-CABs), proton pump inhibitors (PPIs), and H
-receptor antagonists (H
RAs).
A total of 758 patients were included in the final dataset, of which 307 (40%) were administered concomitant pH-regulating drugs while receiving frontline EGFR-TKIs. After adjusting for basic patient characteristics, patients administered gefitinib, erlotinib, afatinib, and osimertinib with concomitant pH-regulating drugs had lower OS than those without concomitant pH-regulating drugs, with hazard ratios of 1.74 (with a 95% confidence interval of 1.34-2.27), 1.33 (0.80-2.22), 1.73 (0.89-3.36), and 5.04 (1.38-18.44), respectively. The 2-year OS rates of patients receiving gefitinib with or without concomitant pH-regulating drugs were 65.4 and 77.5%, those for erlotinib were 55.8 and 66.6%, and those for afatinib were 63.2 and 76.9%, respectively. The 1-year OS rates of patients receiving osimertinib with or without concomitant pH-regulating drugs were 88.1% and 96.9%, respectively.
In addition to the first-generation EGFR-TKIs, the second- and third-generation EGFR-TKIs also resulted in OS deterioration in patients with EGFR mutation-positive NSCLC when used concurrently with pH-regulating drugs.
Abstract
Objective
The introduction of new-generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) has afforded promising overall survival outcomes in clinical trials for ...non-small-cell lung cancer. We aim to investigate the current adoption rate of these agents and the real-world impact on overall survival among institutions.
Methods
In a nationwide retrospective cohort study of 46 Tokushukai Medical Group hospitals in Japan, we analyzed clinical data of consecutive patients with non-small-cell lung cancer receiving EGFR-TKIs between April 2010 and March 2020. Univariate and multivariate Cox regression analyses examined the associations between overall survival and patient/tumor-related factors and first-line EGFR-TKIs.
Results
A total of 758 patients (58.5% females; median age, 73 years) were included. Of 40 patients diagnosed in 2010, 72.5% received gefitinib, whereas 81.3% of 107 patients diagnosed in 2019 received osimertinib as the first-line EGFR-TKI. With a median follow-up of 15.8 months, the median overall survival was 28.4 months (95% confidence interval, 15.3–31.0). In a multivariate Cox regression analysis, age, body mass index, disease status, EGFR mutational status and first-line epidermal growth factor receptor tyrosine kinase inhibitor were identified as significant prognostic factors after adjusting for background factors including study period, hospital volume and hospital type. The estimated 2-year overall survival rates for gefitinib, erlotinib, afatinib and osimertinib were 70.1% (95% confidence interval 59.7–82.4), 67.8% (95% confidence interval 55.3–83.2), 75.5% (95% confidence interval 64.7–88.0) and 90.8% (95% confidence interval 84.8–97.3), respectively. The median time to treatment failure of gefitinib, erlotinib, afatinib and osimertinib were 12.8, 8.8, 12.0 and 16.9 months or more, respectively.
Conclusions
Our real-world data revealed that the swift and widespread utilization of newer-generation EGFR-TKIs in patients with EGFR mutation-positive non-small-cell lung cancer, and that these newer-generation EGFR-TKIs can prolong overall survival regardless of hospital volume or type. Therefore, osimertinib could be a reasonable first choice treatment for these patients across various clinical practice settings.
The use of increasing generations of epidermal growth factor receptor tyrosine kinase inhibitors, particularly the third-generation osimertinib, extended the overall survival of patients with EGFR mutation-positive non-small-cell lung cancer.
Angiotensin II is involved in tumor growth; however, the precise mechanism is not known. Platelets also contribute to tumor growth, and angiotensin II type 1 receptor (AT1) is expressed on the ...platelet surface. We hypothesized that interaction of platelets with tumor cells through AT1 receptor signaling promotes tumor metastasis. B16F1 melanoma cells were intravenously injected into Agtr1a knockout mice ( AT1a −/− ) and wild-type littermates (WT); the AT1a −/− mice exhibited a reduction in lung colonies. Angiotensin II induced expression of P-selectin on platelets in WT but not in AT1a −/− mice. A selective P-selectin neutralizing antibody decreased lung colony numbers in WT but not in AT1a −/− mice. Levels of vascular endothelial growth factor (VEGF) and stromal cell-derived factor 1 (SDF-1) receptor in platelets at metastatic locus were lower in AT1a −/− mice. Treatment of neutralizing antibodies against VEGF and CXCR4 decreased lung colony numbers in WT but not in AT1a −/− mice. In AT1a −/− mice, and both mobilization of progenitor cells expressing CXCR4+ VEGFR1+ cells from bone marrow and their recruitment to lung tissues were suppressed. These results suggest that AT1A signaling plays a critical role in tumor metastasis through P-selectin–mediated interactions of platelets with tumor and endothelial cells and through the AT1A signaling-dependent production of VEGF and SDF-1, which may be involved in mobilization of CXCR4+ VEGFR1+ cells.
Objective To clarify the association between pre-treatment total bilirubin (PTB) level and severe toxicity in patients receiving cisplatin and irinotecan. Methods We analyzed retrospectively the ...relationships of grade 4 neutropenia or grade 3–4 diarrhea and clinical variables including PTB and pre-treatment neutrophil counts (PNC) using a logistic regression model. Results One hundred and twenty-seven patients (93 men, 34 women; median age: 61 years; range: 24–74 years) received cisplatin (60 or 80 mg/m2) on day 1 and irinotecan (60 mg/m2) on days 1 and 8 every 3 weeks or on days 1, 8 and 15 every 4 weeks. Grade 4 neutropenia occurred in 29 patients (23%) and grade 3–4 diarrhea occurred in 13 patients (10%). Grade 4 neutropenia was associated with a higher PTB level (odds ratio: 4.9; 95% confidence interval: 1.4–17.7), a higher cisplatin dose (2.8, 1.0–7.8) and a lower PNC (1.5, 1.0–2.3). Grade 3–4 diarrhea was associated with liver metastasis (11.2, 2.2–57.4), a higher cisplatin dose (5.0, 1.2–21.3) and a lower PNC (2.0, 1.1–3.6). Conclusions PTB level was associated with the severity of neutropenia caused by cisplatin and irinotecan.
PDF
