A Phase II Study of Cisplatin Plus Gemcitabine followed by Maintenance Gemcitabine for Advanced Squamous Non-Small-Cell Lung Cancer: Kyoto Thoracic Oncology Research Group 1302.

BACKGROUND: There has been no study so far on gemcitabine continuous maintenance therapy targeting only squamous non-small-cell lung cancer (NSCLC) patients. This study aimed to assess the efficacy and safety of cisplatin plus gemcitabine followed by maintenance gemcitabine for chemotherapy- naïve Japanese patients with advanced squamous NSCLC. METHODS: The patients received 4 cycles of gemcitabine (1,000 mg/m2, days 1 and 8) and cisplatin (80 mg/m2, day 1) every 3 weeks, followed by gemcitabine alone as maintenance therapy every 3 weeks until disease progression or unacceptable toxicity. The primary end point of the study was progression-free survival (PFS) from the date of registration. RESULTS: From May 2013 to October 2018, 26 patients were enrolled, and 25 patients received ≥1 cycle of planned treatment. Eighteen patients (69.2%) received 4 cycles of cisplatin plus gemcitabine, and 16 patients (61.5%) received ≥1 cycle of maintenance gemcitabine. The median PFS from the date of registration was 5.3 months (95% CI 2.9-7.3 months). In 16 patients who received ≥1 cycle of maintenance gemcitabine, the median PFS from the date of maintenance gemcitabine initiation was 3.8 months (95% CI 2.3-5.2 months). Their median overall survival from the date of registration was 11.9 months (95% CI 7.5-26.5 months). During the maintenance therapy, adverse events (AEs) were mostly Common Terminology Criteria for AE grade 1. CONCLUSIONS: While this trial did not meet the primary endpoint, the sufficient efficacy and feasibility of gemcitabine maintenance therapy were suggested.

[CLINICAL EFFICACY OF SUSTAINED HIGH-EFFICACY DAILY DIAFILTRATION USING A MEDIATOR-ADSORBING MEMBRANE AND DIRECT HEMOPERFUSION WITH A POLYMYXIN B-IMMOBILIZED FIBER COLUMN IN TREATING ACUTE EXACERBATION OF IDIOPATHIC INTERSTITIAL PNEUMONIAS].

OBJECTIVES: The aim of this study is to investigate the clinical outcomes of patients with steroid-resistant acute exacerbation of idiopathic interstitial pneumonias treated with blood purification therapy comprising direct hemoperfusion using a polymyxin B-immobilized fiber column (PMX-DHP) and sustained high-efficacy daily diafiltration using a mediator-adsorbing membrane (SHEDD-fA). METHODS: The clinical outcomes and respiratory function were retrospectively compared between 6 patients who underwent blood purification therapy (blood purification group) and 15 patients (control group) who blood purification therapy. RESULTS: The patients in the blood purification group showed a higher PaO2/FiO2 ratio than those in the control group. Twenty-eight days (83%; 5/6 vs. 20%; 3/15) and ninety days (67%; 4/6 vs. 6.7%; 1/15) survival rates were also higher in the blood purification group. The blood purification group also showed a better 90-day survival curve (Hazard ratio=0.260) compared to the control group. CONCLUSIONS: In conclusion, combination blood purification therapy comprising PMX-DHP and SHEDD-fA may be used to treat acute exacerbation of idiopathic interstitial pneumonias.

[A case of docetaxel-induced acute lung injury refractory to treatment].

A 59-year-old man was diagnosed with squamous cell cancer of the upper lobe of the left lung 11 months before his current admission. The clinical stage was T2N3M1(Stage IV). We started chemotherapy(carboplatin/gemcitabine), which was administered for 7 courses and discontinued 5 months before admission, but he subsequently showed a local relapse. Therefore, we restarted second-line chemotherapy(docetaxel)on admission. Only a single dose of docetaxel was administered, but the patient was diagnosed with respiratory failure 18 days afterwards. The chest roentgenogram and computed tomography showed ground-glass opacities. Bronchoalveolar lavage and blood test data showed no evidence of infection. We diagnosed the patient with acute lung injury induced by docetaxel. The patient was admitted to the intensive care unit, and therapy with steroids and sivelestat was initiated. In addition, artificial respiration, direct hemoperfusion with a polymyxin B-immobilized fiber column, etc., were performed. However, this intensive care regimen was unsuccessful, and the patient died 31 days after docetaxel administration. Docetaxel is generally used in the treatment of non-small-cell lung cancer. However, the present case showed that its use might lead to fatal drug-induced lung injury.

[A case of drug-induced lung injury associated with chemotherapy (FOLFOX6, FOLFIRI, Bevacizumab) for an advanced colon cancer].

A woman in her late sixties had an operation for ascending colon cancer 15 months before her current admission. The pathological finding was T3(mod. SE), N0, H0, P3, M0, Stage IV. She had received chemotherapy after her operation. The first-line therapy comprised 15 courses of FOLFOX6 (from 14 to 5 months before admission). Her second-line chemotherapy comprised 6 courses of FOLFOX6+bevacizumab (BV) (from 3 to 2 months before admission). The third-line chemotherapy comprised 3 courses of FOLFIRI+BV (from 40 to 11 days before admission). She developed a high fever and respiratory failure 3 days before admission. On admission to our hospital, her chest X-ray and CT showed ground-grass opacities in bilateral lung fields. Bronchoalveolar lavage showed a predominance of lymphocytes without any evidence of infection. We diagnosed the patient as a case of lung injury caused by anticancer drugs. Steroid therapy was implemented, and her fever, respiratory failure, and chest X-ray abnormalities disappeared. Steroid therapy was stopped 6 months later and subsequently lung injury did not recur. Judging by the progress seen in this case, we concluded that her lung injury was due to irinotecan. We continued the chemotherapy for her colon cancer by prescribing S-1, it proved ineffective. The patient died from the colon cancer 27 months after her operation.

[Bronchial asthma-like symptoms induced by pulmonary embolism].

A 75-year-old woman who lived in a retirement home was admitted to the emergency room of our hospital because of acute respiratory failure with sudden onset of wheezing on awakening. A differential diagnosis of heart failure, showed that she had experienced an attack of bronchial asthma. She was therefore given beta-agonists via inhalation and theophylline and steroids intravenously. Her wheezing decreased but her respiratory failure persisted. Therefore, she was transferred to the intensive care unit and was referred to our department. Contrast-enhanced computed tomography of her chest showed pulmonary embolisms involving both lower lung lobes. Moreover, pulmonary perfusion scintigraphy showed defects in both lower lobes. Thus, pulmonary embolism was diagnosed. Subsequently, we started anticoagulant therapy, and her respiratory failure was saved. Pulmonary embolism is known to induce symptoms such as bronchial asthma, although such symptoms are rare.

[A case of bronchocentric granulomatosis associated with Aspergillus clusters that was difficult to distinguish from lung cancer].

A 69-year-old man was examined for investigation of a nodular shadow with calcification detected on computed tomography of the chest. He showed no features of allergic bronchopulmonary aspergillosis (ABPA), such as bronchial asthma or eosinophilia. We could not distinguish his disease status from lung cancer and performed upper lobectomy of his right lung. Pathological examination revealed bronchocentric granulomatosis (BCG) with Aspergillus clusters. Subsequent serological testing demonstrated high levels of IgE-RIST and IgE-RAST (Aspergillus) whereas anti-Aspergillus precipitating antibody was not detectable. We believe that Aspergillus clusters may have been present in this patient for several years, and the pathological findings might be manifested as an asymptomatic localized allergic inflammation. BCG is a pathological component of ABPA. This case, of a localized allergic reaction, is considered very valuable for understanding the underlying mechanism of the onset of ABPA.

[A case of pulmonary Mycobacterium abscessus infection with asbestosis in a patient given multidisciplinary treatment].

A 68-year-old man consulted our hospital because of a giant cavity in the upper lobe of the right lung, which was detected in a medical examination for asbestosis. Mycobacterium abscessus was cultured from his sputum in 2 separate cultures. Therefore we diagnosed pulmonary Mycobacterium abscessus infection and prescribed amikacin, imipenem/cilastatin, and clarithromycin. After 2 months, lobectomy of the upper lobe of the right lung was performed. The 3 antibiotics were continued for another 6 months, and the patient recovered completely. Mycobacterium abscessus infection is one of the most intractable non-tuberculous mycobacterial infections, and it is important to include surgery in the primary treatment plan.

[Case of systemic arterio-pulmonary venous fistula detected during a routine group medical checkup].

A 55-year-old man was admitted following the discovery of a radiographic abnormality. A chest radiograph and computed tomography showed a subpleural nodule in the lingular division of the left lung with a dilated pulmonary vein. A pulmonary arteriograph showed no abnormal pulmonary artery in the pulmonary arterial phase, no abnormal pulmonary vein in the pulmonary venous phase, but an abnormal artery (left lateral thoracic artery) from the left subclavian artery with a fistula to the pulmonary vein. A left lateral thoracic arteriograph clearly showed that this artery was dilated and formed a fistula with the pulmonary vein. The patient was given a diagnosis of systemic arterio-pulmonary venous fistula. Such cases are very rare, but some cases with hemoptysis have been reported. The patient was given the option of treatment by operation or embolization, but he refused any therapy.

[A case of pulmonary infection due to Mycobacterium simiae].

A 61-year-old woman presented to our hospital with a chronic cough. She had been diagnosed with pulmonary infection due to non-tuberculous mycobacteria by her previous doctor and had received antimycobacterial chemotherapy for 1 year. Chest radiography and computed tomography on the first visit to our hospital revealed nodular shadows with a cavity in the right upper lung field and infiltrative shadows with bronchiectasis in the lingular segment. Mycobacterium simiae was identified using DNA hybridization methods. Analysis of base sequences from sputum samples using 16S rRNA confirmed the identity of all tested isolates as Mycobacterium simiae, and the organism was isolated repeatedly from sputum mycobacterial tests. Pulmonary infection due to Mycobacterium simiae was diagnosed. Rifampicin, Ethambutol and Clarithromycin were administered to the patient, but clinical symptoms have continued, and findings on chest radiography have deteriorated. Cases of pulmonary infection due to Mycobacterium simiae are rare, and this represents the first such case reported in Japan.

[CT-guided transbronchial diagnosis using ultrathin bronchoscope for small peripheral pulmonary lesions].

We performed computed tomography (CT)-guided transbronchial diagnosis on 23 patients, using an ultrathin bronchoscope (external diameter, 2.8 mm) for small peripheral pulmonary lesions (< or = 2 cm). The mean size of the lesions was 1.4 x 1.1 cm. After examination using a conventional bronchoscope (external diameter, 6.3 mm), an ultrathin bronchoscope and a biopsy apparatus were advanced to the lesion under CT and X-ray fluoroscopic guidance. The location of the biopsy apparatus at each lesion was confirmed by thin-section CT, and a biopsy was performed. The ultrathin bronchoscope reached the 5th-11th bronchus (mean, 7.1 +/- 1.5th), at a point 3.6 +/- 0.9 bronchi peripheral to the site reached using a conventional bronchoscope. In 20 of the 23 patients, the biopsy apparatus could be guided to the lesion. The diagnosis rate, by disease, was 81.8% (9/11) for lung cancer, 66.7% (2/3) for metastatic lung cancer, and 77.8% (7/9) for inflammation; the overall rate being 78.3% (18/23). CT-guided transbronchial diagnosis using an ultrathin bronchoscope is useful for diagnosing small peripheral pulmonary lesions because the bronchoscope can be readily inserted into peripheral areas and guided to lesions, and the site of sample collection can be accurately determined.