To investigate whether ivermectin inhibits SARS-CoV-2 proliferation in patients with mild-to-moderate COVID-19 using time to a negative COVID-19 reverse transcription-polymerase chain reaction ...(RT-PCR) test.
CORVETTE-01 was a double-blind, randomized, placebo-controlled study (August 2020-October 2021) conducted in Japan. Overall, 248 patients diagnosed with COVID-19 using RT-PCR were assessed for eligibility. A single oral dose of ivermectin (200 μg/kg) or placebo was administered under fasting. The primary outcome was time to a negative COVID-19 RT-PCR test result for SARS-CoV-2 nucleic acid, assessed using stratified log-rank test and Cox regression models.
Overall, 112 and 109 patients were randomized to ivermectin and placebo, respectively; 106 patients from each group were included in the full analysis set (male %, mean age: 68.9%, 47.9 years ivermectin; 62.3%, 47.5 years placebo). No significant difference was observed in the occurrence of negative RT-PCR tests between the groups (hazard ratio, 0.96; 95% confidence interval CI 0.70-1.32;
= 0.785). Median (95% CI) time to a negative RT-PCR test was 14.0 (13.0-16.0) and 14.0 (12.0-16.0) days for ivermectin and placebo, respectively; 82.1% and 84% of patients achieved negative RT-PCR tests, respectively.
In patients with COVID-19, single-dose ivermectin was ineffective in decreasing the time to a negative RT-PCR test.
ClinicalTrials.gov, NCT04703205.
Background
Osimertinib is recommended for non‐small cell lung cancer (NSCLC) patients with EGFR mutation; however, it is unclear whether body size variables affect the efficacy of osimertinib in such ...patients. This study assessed the potential effect of body surface area (BSA) and body mass index (BMI) on osimertinib chemotherapy in patients with T790M‐positive advanced NSCLC who progress on prior EGFR‐tyrosine kinase inhibitors (TKIs).
Methods
We conducted a prospective observational cohort study. Median BSA and BMI were used as cut‐off values to evaluate the impact of body size variables on osimertinib chemotherapy.
Results
The median BSA and BMI of 47 patients were 1.50 m2 and 21.5 kg/m2, respectively. Clinical outcomes did not significantly differ between the high and low BSA groups, with response rates of 59.1% and 56.0% (P = 0.83) and progression‐free survival (PFS) of 7.6 and 9.1 months (P = 0.69), respectively. Similarly, there were no significant differences between the high and low BMI groups relative to response rates, which were 60.8% and 54.1% (P = 0.64), respectively, and PFS, which was 7.6 months in both groups (P = 0.38). No significant differences were observed among toxicity profiles in relation to BSA or BMI. Multivariate analysis identified better performance status, young age, and EGFR exon 19 deletion as independent favorable predictors of PFS.
Conclusion
The efficacy of osimertinib does not significantly vary relative to body size variables of patients with T790M‐positive NSCLC who progress on prior EGFR‐TKIs.
Background
The standard treatment for patients with unresectable locally advanced (LA) non‐small cell lung cancer (NSCLC) is chemoradiotherapy (CRT). Consolidation therapy with durvalumab after CRT ...demonstrated survival benefits and was approved in Japan in July 2018. The use of immune checkpoint inhibitors (ICIs) is entering routine oncological practice, and here we investigate the feasibility of concurrent CRT for LA‐NSCLC patients based on the PACIFIC criteria.
Methods
We performed a retrospective study to evaluate the feasibility and efficacy of concurrent CRT prior to the approval of durvalumab. We assessed consecutive patients with LA‐NSCLC treated with CRT between January 2012 and June 2018.
Results
We analyzed a total of 108 consecutive patients who received radical thoracic radiotherapy and concurrent platinum‐based chemotherapy. Of those patients, 105 (97%) completed the planned radiotherapy. Radiation pneumonitis was observed in 93 patients (85%), with a median of 130 days (range: 41–317 days) from the initiation of radiation to the onset of the complication. Among the patients, 74 (69%) were considered eligible for consolidation therapy with durvalumab. The overall response rate was 64%, and the two‐year survival rate was 63%. Patients who received an ICI after relapse were associated with significantly better survival than those who did not receive an ICI (two‐year survival rate: 87% vs. 41%, respectively; P = 0.001).
Conclusions
Prior to the approval of durvalumab, the clinical application of ICIs improved the outcome of patients with relapsed NSCLC after CRT for LA‐NSCLC. The management of radiation pneumonitis remains a challenge following the approval of durvalumab.
Amrubicin has been demonstrated to be beneficial in the treatment of patients with relapsed small cell lung cancer (SCLC). The aim of the present study was to evaluate whether there is a significant ...difference in the efficacy of amrubicin between patients with relapsed SCLC who were previously treated with a platinum agent in combination with a topoisomerase I inhibitor, and those patients previously treated with a platinum agent in combination with a topoisomerase II inhibitor. The medical records of patients with SCLC, who were diagnosed as having relapsed following treatment with a platinum-based regimen and subsequently received amrubicin monotherapy, were retrospectively reviewed. Of a total of 48 patients with SCLC who were treated with amrubicin, the overall response rate, median progression-free survival (PFS) time and median survival time (MST) were determined to be 31.3%, 7.1 and 17.0 months, respectively. The response rate, PFS time and MST did not differ significantly between the patients treated previously with a platinum agent in combination with irinotecan, a topoisomerase I inhibitor, (36.4%, 5.7 and 11.4 months, respectively) and those treated previously with a platinum agent in combination with etoposide, a topoisomerase II inhibitor (30.0%, 4.7 and 14.8 months, respectively). The results indicate that amrubicin may be effective as a second-line chemotherapeutic agent for patients with SCLC, irrespective of which platinum agent and topoisomerase inhibitor-based chemotherapy regimen was previously administered.
It is unclear whether there is a difference in the efficacy of treatment by epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) between patients with postoperative recurrent ...non-small-cell lung cancer (NSCLC) and those with stage IV NSCLC harboring EGFR mutations.
The records of NSCLC patients harboring EGFR mutations who were treated with gefitinib or erlotinib were retrospectively reviewed, and the treatment outcomes were evaluated. Moreover, we performed an immunohistochemical analysis of PD-L1 expression in tumor lesions of the postoperative recurrence group.
In 205 patients, both the progression-free survival (PFS) time (9.4 vs. 16.9 months) and the median survival time (24.7 vs. 37.4 months) were significantly longer in the postoperative group than in the stage IV group. Additionally, multivariate analysis identified that postoperative recurrence was an independent predictor of PFS and overall survival, as were performance status and smoking status. The PFS durations were 15.7 and 16.6 months for the high- and low-PD-L1 expression groups, respectively, and no significant difference was observed (P = 0.73).
The findings of this study provide a valuable rationale for considering postoperative recurrence as a predictive factor for favorable PFS and overall survival in patients with NSCLC harboring activating EGFR mutations who receive EGFR-TKIs.
Background
Treatment strategies for patients with non‐small cell lung cancer (NSCLC) depend on various factors including physical condition, complications, tumor histology, and molecular profiling. ...Even if initial chemotherapy is efficacious, almost all patients develop treatment resistance. Invasive rebiopsy from sites of recurrence might provide insight into resistance mechanisms and aid in the selection of suitable sequential antitumor drugs. However, invasive rebiopsy might be challenging because of limited tissue availability and patient burden. Therefore, this study aimed to assess awareness of invasive rebiopsy among non‐small cell lung cancer patients.
Methods
This prospective questionnaire survey was performed between June 2015 and March 2016 in patients with advanced non‐small cell lung cancer. The survey was carried out at two time points: before starting first‐line chemotherapy (cohort 1), and at the time of disease progression after initial chemotherapy, but before second‐line chemotherapy (cohort 2).
Results
In this study, 50 and 30 patients were enrolled in cohorts 1 and 2, respectively. In cohort 1, 37 (74%) patients agreed to rebiopsy, if disease progression occurred, whereas 18 (60%) patients in cohort 2 agreed to invasive rebiopsy at disease progression. The primary reasons for rebiopsy rejection were poor physical condition and patient burden related to the initial biopsy. Seven patients answered the survey questions during the treatment course, and the acceptance rate was lower among patients who agreed to rebiopsy at disease progression than before treatment.
Conclusions
Invasive rebiopsy can lead to distress in some patients. To improve the consent rate for tissue rebiopsy, treatment strategies including rebiopsy should be discussed with patients during the early treatment phase.
Experiments were performed to evaluate the hypothesis that ACE (angiotensin-converting enzyme) inhibition (enalapril) suppresses 3-NT (3-nitrotyrosine) production in the renal cortex during the early ...stage of Type 1 DM (diabetes mellitus) in the rat. Enalapril was administered chronically for 2 weeks to subsets of STZ (streptozotocin)-induced DM and vehicle-treated sham rats. O(2)(-) (superoxide anion) and NO(x) (nitrate+nitrite) levels were measured in the media bathing renal cortical slices after 90 min incubation in vitro. SOD (superoxide dismutase) activity and 3-NT content were measured in the renal cortex homogenate. Renal cortical nitrated protein was identified by proteomic analysis. Renal cortical production of O(2)(-) and 3-NT was increased in DM rats; however, enalapril suppressed these changes. DM rats also exhibited elevated renal cortical NO(x) production and SOD activity, and these changes were magnified by enalapril treatment. 2-DE (two-dimensional gel electrophoresis)-based Western blotting revealed more than 20 spots with positive 3-NT immunoreactivity in the renal cortex of DM rats. Enalapril treatment blunted the DM-induced increase in tyrosine nitration of three proteins ACO2, GDH1 and MMSDH (aconitase 2, glutamate dehydrogenase 1 and methylmalonate-semialdehyde dehydrogenase), each of which resides in mitochondria. These data are consistent with enalapril preventing DM-induced tyrosine nitration of mitochondrial proteins by a mechanism involving suppression of oxidant production and enhancement of antioxidant capacity, including SOD activation.
Background
Despite the literature indicating adverse interactions between warfarin and cytotoxic agents, whether such an interaction occurs when warfarin and gefitinib are used concomitantly is ...unknown. We analyzed the prevalence of the concomitant use of warfarin and gefitinib, and the incidence of prothrombin time-international normalized ratio (PT-INR) alterations or adverse interactions in concomitant users of warfarin and gefitinib.
Methods
We conducted a retrospective study of patients with non-small cell lung cancer treated at the Kitasato University Hospital who received concomitant warfarin and gefitinib between September 2002 and January 2007. Medical information, including the indication for warfarin use, warfarin dosing and dosing changes, and exposure to gefitinib were collected from computerized databases and medical records.
Results
Twelve (4.1%) of 296 patients treated with gefi— tinib received warfarin. PT-INR elevation occurred in 6 patients (50.0%). Two (16.7%) of the 12 patients had liver metastases. Liver dysfunction was associated with PT-INR elevation (
P
= 0.0100).
Conclusion
As there is a possibility of PT-INR abnormalities occurring during the concomitant use of gefitinib and warfarin, clinicians should be aware of this interaction. Because of the potentially severe consequences of this interaction, close monitoring of PT-INR and warfarin dose adjustment are recommended for patients receiving warfarin and gefitinib, especially during the first 2 weeks in the beginning of warfarin therapy.
Background
This study was conducted to evaluate the efficacy of amrubicin as first-line chemotherapy for elderly and poor-risk patients with extensive-disease small-cell lung cancer (ED-SCLC).
...Methods
Untreated SCLC patients who were >75 years of age or had a performance status of 2 or more were eligible. Amrubicin (35 or 40 mg/m
2
on days 1–3 every 3 weeks) was administered.
Results
Between January 2003 and May 2009, 27 patients were evaluated. The median number of treatment cycles was 4 (1–6). Grade 3 or 4 hematologic toxicities comprised neutropenia (63%), leukopenia (56%), thrombocytopenia (15%), and anemia (19%). Febrile neutropenia was observed in four (15%) patients. No treatment-related deaths occurred. The nonhematologic toxicities were mild. The overall response rate was 70%. Progression-free survival, median survival time, and the 1-year survival rate were 6.6 months, 9.3 months, and 30%, respectively. The 40 mg/m
2
dose was feasible and had a tendency to be more effective than the 35 mg/m
2
dose.
Conclusions
Amrubicin exhibits activity and acceptable toxicities for elderly and poor-risk patients with ED-SCLC in the first-line treatment setting.
and objective: This study examined the validity of sniff nasal inspiratory (SNIP) and reverse-sniff nasal expiratory pressures (RSNEP) for estimating respiratory muscle strength and for predicting ...poor life expectancy following exacerbation in patients with chronic obstructive pulmonary disease (COPD).
This prospective study included patients who were admitted for COPD exacerbation and underwent rehabilitation. At hospital discharge, SNIP, RSNEP, and maximum mouth inspiratory (MIP) and expiratory pressures (MEP) were measured, and the body mass index, degree of airflow obstruction, dyspnea, and exercise capacity (BODE) index was calculated by evaluating body mass index, forced expiratory volume in 1 s (FEV
), the Modified Medical Research Council Dyspnea Scale, and 6-min walk distance.
Data from 43 patients (mean age 76.8 years, FEV
42.8 % predicted) were analyzed. SNIP and RSNEP were moderately correlated with MIP and MEP, respectively. Bland-Altman plot means of SNIP (48.3 ± 17.5) and RSNEP (44.7 ± 23.8 cmH
O) were lower than those of MIP (54.8 ± 19.9) and MEP (76.4 ± 31.2 cmH
O), respectively, and the SNIP-MIP and RSNEP-MEP 95 % limits of agreement were wide. Logistic regression showed that SNIP and RSNEP were significantly associated with BODE score ≥7 (poor life expectancy), and predictive accuracy was 81.4 % when combining SNIP ≤49 and RSNEP ≤42 cmH
O.
After exacerbation in patients with COPD, SNIP and RSNEP are useful indicators that complement MIP and MEP. Furthermore, a combined SNIP and RSNEP test may be beneficial in predicting poor life expectancy.
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