Severe esophagitis directly induced by accumulation of crizotinib-residue at the esophageal mucosa proven with polarizing microscope examination

Crizotinib demonstrates dramatic effects for the patients with echinoderm microtubule-associated protein-like 4 (EML4)-anaplastic lymphoma kinase gene (ALK) fusion or c-ros oncogene 1 (ROS-1) fusion-positive lung cancer, with some characteristic toxicities. Although several studies reported that serious esophagitis was induced by crizotinib, the detailed mechanisms and ways to ameliorate the esophagitis have not been clarified. In this report, we report two cases with lung cancer who had been treated with crizotinib and developed severe esophagitis. Polarizing microscope examination clearly revealed that the accumulation of crizotinib-residue in the esophageal biopsy samples at the second anatomical narrowing of the esophagus in both cases. Since it seemed that the accumulation of crizotinib-residue in the esophageal mucosa directly caused the esophageal inflammation, we recommended taking crizotinib with a large amount of water (more than 200 ml) and to stay sitting upright for 30 minutes after intake. After that, the esophagitis gradually improved and the patients could continue taking crizotinib without dose reduction or withdrawal. Our experiences suggest that this crizotinib-induced esophagitis could be easily prevented by proper administration of crizotinib

Real-World Incidence of Febrile Neutropenia among Patients Treated with Single-Agent Amrubicin: Necessity of the Primary Prophylactic Administration of Granulocyte Colony-Stimulating Factor

Background: Single-agent amrubicin chemotherapy is a key regimen, especially for small cell lung cancer (SCLC); however, it can cause severe myelosuppression. Purpose: The purpose of this study was to determine the real-world incidence of febrile neutropenia (FN) among patients treated with single-agent amrubicin chemotherapy for thoracic malignancies. Patients and methods: The medical records of consecutive patients with thoracic malignancies, including SCLC and non-small cell lung cancer (NSCLC), who were treated with single-agent amrubicin chemotherapy in cycle 1 between January 2010 and March 2020, were retrospectively analyzed. Results: One hundred and fifty-six patients from four institutions were enrolled. Their characteristics were as follows: median age (range): 68 (32–86); male/female: 126/30; performance status (0/1/2): 9/108/39; SCLC/NSCLC/others: 111/30/15; and prior treatment (0/1/2/3-): 1/96/31/28. One hundred and thirty-four (86%) and 97 (62%) patients experienced grade 3/4 and grade 4 neutropenia, respectively. One hundred and twelve patients (72%) required therapeutic G-CSF treatment, and 47 (30%) developed FN. Prophylactic PEG-G-CSF was not used in cycle 1 in any case. The median overall survival of the patients with FN was significantly shorter than that of the patients without FN (7.2 vs. 10.0 months, p = 0.025). Conclusions: The real-world incidence rate of FN among patients with thoracic malignancies that were treated with single-agent amrubicin chemotherapy was 30%. It is suggested that prophylactic G-CSF should be administered during the practical use of single-agent amrubicin chemotherapy for patients who have already received chemotherapy

Evaluation of a Triage Checklist for Mild COVID-19 Outpatients in Predicting Subsequent Emergency Department Visits and Hospitalization during the Isolation Period: A Single-Center Retrospective Study

Managing mild illness in COVID-19 and predicting progression to severe disease are concerning issues. Here, we investigated the outcomes of Japanese patients with mild COVID-19, and identified triage risk factors for further hospitalization and emergency department (ED) visits at a single tertiary hospital. A triage checklist with 30 factors was used. Patients recommended for isolation were followed up for 10 days for subsequent ED visits or hospital admission. Overall, 338 patients (median age, 44.0; 45% women) visited the clinic 5.0 days (median) after symptom onset. Thirty-six patients were immediately hospitalized following triage; others were isolated. In total, 72 non-hospitalized patients visited the ED during their isolation, and 30 were hospitalized after evaluation for oxygen desaturation. The median ED visit and hospitalization durations after symptom onset were 5.0 and 8.0 days, respectively. The checklist factors associated with hospitalization during isolation were age > 50 years, body mass index > 25 kg/m2, hypertension, tachycardia with pulse rate > 100/min or blood pressure > 135 mmHg at triage, and >3-day delay in hospital visit after symptom onset. No patients died. Altogether, 80% of patients with mild COVID-19 could be safely isolated at home. Age, BMI, underlying hypertension, date after symptom onset, tachycardia, and systolic blood pressure at triage might be related to later hospitalization

Phase II trial of erlotinib in patients with advanced non-small-cell lung cancer harboring epidermal growth factor receptor mutations: additive analysis of pharmacokinetics

Background: We conducted a phase II trial of erlotinib in patients with advanced non-small-cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations and evaluated the relationship between plasma concentration and efficacy of erlotinib. Methods: Patients who were previously treated but naive to epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs), with advanced NSCLC harboring EGFR mutations, were enrolled. Erlotinib was given at 150 mg once daily until disease progression. The primary end point was objective response rate (ORR). Plasma trough levels of erlotinib were measured on Days 2 (D2) and 8 (D8) by high-performance liquid chromatography. Results: In total, 29 patients were enrolled from September 2008 to January 2011. ORR was 61.5 % (95 % confidence interval [CI] 40.57-79.8) of 26 assessable patients. The median progression-free survival (PFS) and overall survival (OS) were 6.3 months and 16.9 months, respectively. Skin rash was observed in 24 patients, mostly at grade 1 or 2. Grade 2 pneumonitis was observed in one patient. We collected blood samples from 16 patients. The median PFS of the high and low D8/D2 ratio group was 11.2 months and 5.7 months, respectively (p = 0.044, hazard ratio = 0.301, 95 % CI 0.094-0.968). Conclusion: Erlotinib showed an ORR comparable to that seen in previous studies for patients with NSCLC harboring EGFR mutations, although response, the primary end point, did not reach the predetermined threshold level. The D8/D2 ratio of erlotinib plasma trough levels might be a predictive factor for PFS