Complete remission of advanced lung adenocarcinoma with first-line pembrolizumab monotherapy: Two case reports.

Immune checkpoint inhibitors (ICIs) are clinically used for treating advanced lung cancer, and some patients have achieved complete remission (CR) with ICI therapy in clinical trials. However, reports summarizing the clinical courses of such patients are limited. We report two cases of lung adenocarcinoma in which CR was achieved with first-line pembrolizumab monotherapy, and the therapeutic effect was maintained after treatment completion. Specific patients can achieve CR, even those who do not meet the previously reported predictors of treatment response other than high programmed death-ligand 1 expression. Thus, biomarkers that can accurately predict the clinical efficacy of ICIs are warranted.

A phase II study of S-1 and cisplatin with concurrent thoracic radiotherapy followed by durvalumab for unresectable, locally advanced non-small-cell lung cancer in Japan (SAMURAI study).

BACKGROUND: Based on the results of the PACIFIC study, chemoradiotherapy followed by 1-year consolidation therapy with durvalumab was established as the standard of care for unresectable, locally advanced non-small-cell lung cancer (LA-NSCLC). However, some topics not foreseen in that design can be explored, including progression-free survival (PFS) and overall survival (OS) after the start of chemoradiotherapy, the proportion of patients who proceeded to consolidation therapy with durvalumab, and the optimal chemotherapeutic regimens. In Japan, the combination regimen of S-1 + cisplatin (SP), for which the results of multiple clinical studies have suggested a good balance of efficacy and tolerability, is frequently selected in clinical settings. However, the efficacy and safety of consolidation therapy with durvalumab following this SP regimen have not been evaluated. We therefore planned a multicenter, prospective, single-arm, phase II study. METHODS: In treatment-naïve LA-NSCLC, two cycles of combination chemotherapy with S-1 (80-120 mg/body, Days 1-14) + cisplatin (60 mg/m2, Day 1) will be administered at an interval of 4 weeks, with concurrent thoracic radiotherapy (60 Gy). Responders will then receive durvalumab every 2 weeks for up to 1 year. The primary endpoint is 1-year PFS rate. DISCUSSION: Compared with the conventional standard regimen in Japan, the SP regimen is expected to be associated with lower incidences of pneumonitis, esophagitis, and febrile neutropenia, which complicate the initiation of consolidation therapy with durvalumab, and have higher antitumor efficacy during chemoradiotherapy. Therefore, SP-based chemoradiotherapy is expected to be successfully followed by consolidation therapy with durvalumab in more patients, resulting in prolonged PFS and OS. Toxicity and efficacy results of the SP regimen in this study will also provide information important to the future establishment of the concurrent combination of chemoradiotherapy and durvalumab. TRIAL REGISTRATION: Japan Registry of Clinical Trials, jRCTs031190127, registered 1 November 2019, https://jrct.niph.go.jp/latest-detail/jRCTs031190127.

Acute Respiratory Failure Caused by Pulmonary Lymphangitic Carcinomatosis in a Patient With Lung Adenocarcinoma at Initial Diagnosis / Insuficiencia respiratoria aguda causada por linfangitis carcinomatosa pulmonar en un paciente con adenocarcinoma de pulmón desde el diagnóstico inicial

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[Measures to Ensure Safety of Docetaxel plus Ramucirumab for Advanced Non-Small-Cell Lung Cancer as the Second- or Later-Line].

With the standpoint ofref ining the chemotherapy regimen, we retrospectively reviewed adverse events encountered by the initial 10 cases during the first course of docetaxel plus ramucirumab for non-small-cell lung cancer that progressed after platinum-based chemotherapy. Febrile neutropenia(FN)was observed in 40% ofcases, and a halfofall patients experienced oral mucositis, including 2 Grade 3 cases. These results were concordant with a previous randomized phaseⅡstudy on Japanese patients. We amended the treatment regimen by adding the prophylactic use ofpegf ilgrastim. Post-amendment, FN was not observed in all 10 cases. However, the frequency and severity of chemotherapy-induced oral mucositis were not affected; Therefore, some patients discontinued treatment due to this toxicity as well as diarrhea. In conclusion, prophylactic granulocyte-colony stimulating factor is considered effective for reducing the risk of FN. Further intervention by an oral care team is required to validate our findings.

Curative thoraco-systemic therapy plus local treatment to the brain for extensive disease-small-cell lung cancer with metastasis only to the brain.

We reviewed 11 cases of extensive disease (ED)-SCLC and metastasis only to the brain treated during 2011-14. All patients underwent definitive therapy similar to that for limited disease (LD), combined with local treatment for BM. We compared the survival outcomes of these patients to those of patients with LD (n = 29) or other ED (n = 38) during the same period. Three patients had progression of BM at completion of chemotherapy. Ten patients received whole-brain radiotherapy (4 prophylactic, 6 therapeutic), and remaining one elderly patient underwent stereotactic radiosurgery. Finally, 8 and 3 patients achieved a CR or PR of BM, respectively. Five remained free of progression for 21.1-73.2 months. The progression-free and overall survival outcomes of ED-SCLC with brain only metastases were comparable to those of LD and superior to those of other ED. In conclusion, ED-SCLC with metastasis limited to the brain could be treated with curative intent.

A case of adult-onset type II citrullinemia induced by hospital diet.

A 47-year-old Japanese man was first admitted to our hospital for 8 days because of an asthma attack. After discharge he changed his diet. On the 12th day after his discharge, he was re-admitted to our hospital because he exhibited transient loss of consciousness with flapping tremor. His plasma ammonia level was extremely high (245 µg/dL; normal, <90 µg/dL), suggesting hepatic encephalopathy. He underwent intravenous administration of branched-chain amino acids (Aminoleban(®)) and oral administration of lactulose and kanamycin sulfate; however, the hyperammonemia did not improve. Analysis of the amino acids and citrin gene led to the diagnosis of adult-onset type II citrullinemia (CTLN2). Following this diagnosis, the carbohydrate content of his diet was mildly restricted. As a result, his plasma ammonia level markedly improved (ammonia, 40-60 µg/dL) and he became symptom-free without any medication. CTLN2 is a metabolic disorder characterized by increased plasma concentrations of citrulline and ammonia, which occurs by the failure of compensatory mechanisms associated with diet. Here, we report a case of a patient for whom a change in eating habits during his hospitalization disturbed his compensatory mechanism resulting in clinical CTLN2, which was reversed with an appropriate diet.

Randomized phase II trial of OK-432 in patients with malignant pleural effusion due to non-small cell lung cancer.

To determine the optimum dose of OK-432 for intrathoracic administration, a multicenter randomized phase II trial was conducted in patients with malignant pleural effusion due to non-small cell lung cancer. Patients with histologically- or cytologically-proven malignant pleural effusions were randomized to arm A (10 Klinische Einheit (KE) of OK-432) or arm B (1 KE of OK-432). OK-432 was injected intrapleurally over 30 min on days 1 and 3 and the chest tube was clamped for 6 h. If control was inadequate on day 8, 10 KE was administered on days 8 and 10 in each treatment arm. Forty patients were enrolled and 38 patients were eligible (19 in arm A and 19 in arm B). The effusion control rate on day 8 was 79% in arm A and 53% in arm B, while control rates on day 28 were 74% and 84%, respectively. The median drainage time after administration was significantly shorter in arm A (4.0 +/- 1.2 days) than in arm B (7.0 +/- 1.7 days). The total drainage volume was also significantly less in arm A than in arm B. No grade 4 toxicities or treatment-related deaths were observed in either treatment arm. Intrathoracic injection of OK-432 is a feasible treatment for malignant pleural effusion. Although the malignant pleural effusion control rate was equivalent in each treatment arm, faster control and less drainage were achieved in arm A. A dose of OK-432 10 KE/body is, therefore, recommended for further trial.

Importance of atopic cough, cough variant asthma and sinobronchial syndrome as causes of chronic cough in the Hokuriku area of Japan.

OBJECTIVE: A prospective multicentre study was conducted to elucidate the causes of chronic cough in Japan. METHODOLOGY: All consecutive and unselected patients complaining of cough lasting 8 weeks or more, who visited our clinics from 1 June to 31 December 2001, were registered. The causes of chronic cough were diagnosed based on the criteria for definite and probable causes of cough as recommended by the Japanese Cough Research Society. RESULTS: Of the 248 patients enrolled, 72 patients (29.0%) were unavailable for follow up before their diagnostic assessment had been finalized. Among the 176 patients who were adequately assessed, a diagnosis was made in 165 patients (93.7%) either as single cause or as one of two causes: atopic cough in 48 (29.1%) and 11 patients (6.7%); cough variant asthma in 46 (27.9%) and nine patients (5.5%); cough predominant asthma in 14 (8.5%) and three patients (1.8%); and sinobronchial syndrome (SBS) in 28 (17.7%) and 14 patients (8.5%), respectively. A diagnosis of gastro-oesophageal reflux-associated cough was made in a total of four patients (2.4%). CONCLUSION: Atopic cough, asthmatic cough consisting of cough variant asthma and cough predominant asthma, and SBS are major causes of chronic cough in Japan.

A phase I study of carboplatin and docetaxel for advanced non-small cell lung cancer using the continual reassessment method.

PURPOSE: This phase I study was designed to determine the maximum tolerated dose of carboplatin combined with a fixed dose of docetaxel (60 mg/m(2)) and the safety and efficacy of this combination chemotherapy in unresectable non-small cell lung cancer. METHODS: Patients received a 60 min intravenous infusion of docetaxel followed by a 90 min infusion of carboplatin with dose escalation using the continual reassessment method. The starting dose of carboplatin was targeted to an area under the plasma concentration curve of 3 using Calvert's equation and dose escalation was based on course 1 toxicities. RESULTS: From January 1999 to February 2000, 16 patients entered this trial. The major dose-limiting toxicity was neutropenia. Thrombocytopenia was rare and major non-hematological toxicities included fever that was not associated with neutropenia and grade 2 nausea and vomiting. Objective responses were seen in five patients (response rate 31.3%). CONCLUSIONS: Based on this phase I clinical trial, the maximum tolerated dose of carboplatin combined with 60 mg/m(2) of docetaxel was a target area under the plasma concentration curve (tAUC) of 6 and the recommended tAUC for further trials is 5.5. This combination appeared to be effective for non-small cell lung cancer. A phase II clinical trial is recommended using 60 mg/m(2) of docetaxel and carboplatin with a tAUC of 5.5.