A retrospective study evaluating efficacy and safety of compassionate use of tocilizumab in 13 patients with severe-to-critically ill COVID-19: analysis of well-responding cases and rapidly-worsening cases after tocilizumab administration

We administered tocilizumab into 13 severe-to-critically ill patients with coronavirus disease 2019 (COVID-19) for compassionate use in combination with potential anti-viral agents in those who required an oxygen supply and showed increased laboratory inflammatory markers such as C-reactive protein (CRP) and ferritin. One injection of tocilizumab led to rapid improvements in clinical features, inflammatory findings, and oxygen supply in seven patients with severe COVID-19 and substantial amelioration in two patients who were critically ill, whereas four patients, who exhibited rapidly worsened respiratory function, required artificial ventilatory support even after tocilizumab treatment. Three of these four patients ultimately recovered from deterioration after methylprednisolone treatment. Administration of tocilizumab did not affect viral elimination nor IgG production specific for the virus. Compared with well-responding patients, rapidly-worsened patients showed a significantly higher ratio of ferritin vs. CRP. These findings suggest that tocilizumab has beneficial effects in severe-to-critically ill patients with COVID-19; however, in some cases, addition of methylprednisolone is required for disease rescue.

A case of reversible disturbance of consciousness following leptomeningeal metastases

<b>Introduction：</b>Hyponatremia, which is frequently present in patients with end-stage cancer, causes delirium and disturbance of consciousness and is considered a poor prognostic factor. We report a case of hyponatremia with hypopituitarism in association with leptomeningeal metastasis, resulting in reversible disturbance of consciousness. <b>Case report：</b>A 77 year-old female received chemotherapy at our hospital for postoperative recurrence of lung cancer, and best supportive care due to a side effect. After transfer to another hospital, she experienced a sudden disturbance of consciousness and was returned to our hospital. A detailed examination resulted in a diagnosis of hyponatremia from hypopituitarism following leptomeningeal metastasis involving the cerebral ventricles. Hyponatremia was improved by NaCl supplement and hormone replacement, followed by recovery from disturbance of consciousness. <b>Discussion：</b>QOL of patients with end-stage cancer can be improved through the active treatment of reversible causes of disturbance of consciousness.<b> Conclusion：</b>When severe hyponatremia is detected in cancer patients, it is important to consider the possibility of hypopituitarism with brain metastasis or meninges dissemination in the differential diagnosis.

The relationship between tyrosine kinase inhibitor therapy and overall survival in patients with non-small cell lung cancer carrying EGFR mutations / 癌症

For patients with epidermal growth factor receptor (EGFR) mutation-positive lung cancer, the relationship between the dose or duration of treatment with tyrosine kinase inhibitor (TKI) and overall survival remains unclear. Here, we analyzed clinical data of 39 patients who were diagnosed with EGFR mutation-positive non-small cell lung cancer and treated with TKI, but subsequently died. Several parameters were measured in this study: overall survival; first, second, and overall TKI therapy durations; first TKI intensity (actual dose/normal dose); and TKI rate (overall TKI therapy duration/overall survival). The response rate to TKI therapy was 50%, and the median survival was 553 days. After TKI therapy failed, 38.5% patients were re-challenged with TKI. We observed a moderate relationship [r = 0.534, 95% confidential interval (CI) = 0.263 to 0.727, P < 0.001] between overall TKI therapy duration and overall survival. However, we found no relationship between overall survival and first TKI intensity (r = 0.073, 95% CI = -0.380 to 0.247, P = 0.657) or TKI rate (r = 0.0345, 95% CI = -0.284 to 0.346, P = 0.835). Non-small cell lung cancer patients with mutation-positive tumors remained on TKI therapy for, on average, 33% of the overall survival time. These findings suggest that patients with EGFR mutation-positive tumors should not stick to using TKIs.

The salvage regimen for patients with advanced non-small cell lung cancer who failed prior chemotherapy: once-daily single oral agent Iressa / 中国肺癌杂志

<p><b>BACKGROUND</b>To summarize the effect of Iressa for refractory patients with advanced non small cell lung cancer (NSCLC) failed to prior chemotherapy.</p><p><b>METHODS</b>Thirty-one patients, with unresectable stage IIIB or IV NSCLC who had disease progression or relapse after prior chemotherapy using platinum-based regimen for at least 2 cycles, were admitted to the Osaka Prefectural Hobikino Hospital. Iressa 250 mg was administered once a day until disease progression was noted. Weekly chest x-ray and monthly CT scan were performed for response assessment each month.</p><p><b>RESULTS</b>Among the 31 patients, one complete response (CR) and 7 partial responses (PR) were observed. CR rate was 3.2% (95% confidence interval: 0-17%), PR rate 22.6% (95% confidence interval: 10%-41%), disease control rate including both tumor responses and stable disease was 80.6% (95% confidence interval: 52%-92%). The rate of symptoms relieves was 51.6% (95% confidence interval: 33%-70%), the most effective symptoms being cough and pain. The median time to improved symptoms was 14 days. The most common adverse events were grade I or II skin rash and diarrhea which were readily manageable and reversible. No patients were withdrawn due to the adverse events</p><p><b>CONCLUSIONS</b>Monotherapy using Iressa is effective and tolerable for the patients with advanced NSCLC who failed prior chemotherapy.</p>