Phase II study of amrubicin, 9-amino-anthracycline, in patients with advanced non-small-cell lung cancer: a West Japan Thoracic Oncology Group (WJTOG) study.

PURPOSE: We conducted a multicenter phase II study of amrubicin, a novel 9-aminoanthracycline, to evaluate its efficacy and safety in patients with non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Entry requirements included cytologically or histologically proven measurable NSCLC, stage III or IV, no prior therapy, an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2, and adequate organ function. Amrubicin was given by daily intravenous injection at 45 mg/m2/day for three consecutive days, repeated at 3 week intervals. Each patient received at least three treatment cycles. RESULTS: Sixty-two patients were enrolled in this study. Of the 62 registered patients, 60 were eligible and assessable for efficacy, and 59 for toxicity. Overall response rate was 18.3% (95% confidence interval [CI], 9.5 to 30.4%) and median survival time was 8.2 months (95% CI, 6.7 to 10.4 months). Major toxicity was myelosuppression, with incidences of grade 3 or 4 toxicity of 78.0% for neutropenia, 54.2% for leukopenia, 30.5% for anemia, and 28.8% for thrombocytopenia. Non-hematological toxicities with a greater than 50% incidence were anorexia (69.5%), nausea/vomiting (55.9%), and alopecia (75.9%), but were relatively mild, with grade 3 toxicities observed in only one patient each (1.7%). CONCLUSION: Amrubicin was an active, well-tolerated agent in the treatment of NSCLC.

Analysis of incomplete quality of life data in advanced stage cancer: a practical application of multiple imputation.

This paper presents a practical approach to analyzing incomplete quality of life (QOL) data that contains non-ignorable dropouts in patients with advanced non-small-cell lung cancer (NSCLC). QOL scores for the physical domain at baseline and at the end of the first and second courses of chemotherapy were compared between two treatment groups in a phase III trial. One hundred and 103 eligible patients were randomized to receive cisplatin and irinotecan (CPT-P) or cisplatin and vindesine, respectively; of those two groups, 83 and 85, respectively, completed a QOL questionnaire at least at baseline. A multiple imputation incorporating auxiliary QOL variables was implemented as one of alternatives of sensitivity analyses; these were complete case, available case, and pattern mixture analyses. Although larger sensitivity to missing data was found for CPT-P treatment, none of the alternative analyses demonstrated a significant difference in estimated slopes over time between the groups. This study presents an analytical approach for dealing with the complex problem of missing QOL data. It must be noted, however, that the validity of the multiple imputation method we present is not certain unless we can specify sufficiently informative auxiliary variables to ensure the conversion of non-ignorable missingness to ignorable.

Clinical features of eleven cases of Mycobacterium avium-intracellulare complex pulmonary disease associated with pneumoconiosis.

The relationship between silicosis and tuberculosis is well known. Also other mycobacteria such as Mycobacterium kansasii often occur in association with pneumoconiosis. However, there are few reports describing an association of M. avium-intracellulare complex (MAC) lung disease and pneumoconiosis. The purpose of the present study is to describe clinical features of MAC respiratory infection associated with pneumoconiosis. Eleven patients with MAC respiratory infection associated with pneumoconiosis (all men, 6 with silicosis and 5 with welders' pneumoconiosis) were collected. A determination of whether or not MAC caused pulmonary disease was made using the 1997 criteria required by the American Thoracic Society. Radiologically, cavity formation as well as upper lung field predominance of MAC disease were observed in 8 of 11 cases (72.7%). Two of 11 patients died of respiratory failure. Our present study clearly demonstrates that clinical features of MAC respiratory infection associated with pneumoconiosis were different from MAC without underlying diseases.

Influence of clinical parameters on quality of life during chemotherapy in patients with advanced non-small cell lung cancer: application of a general linear model.

OBJECTIVE: The aim of this study was to determine the relative influence of physician-assessed clinical parameters, including non-hematological adverse events and performance status, on quality of life (QOL) during chemotherapy. METHODS: QOL questionnaires consisting of four domains (functional, physical, mental and psychosocial) were self-administered every week during chemotherapy by patients with advanced non-small cell lung cancer in two phase III clinical trials; 377 patients who completed the questionnaires at baseline and at least once during the first course of therapy were analyzed. A general linear model was applied, where the four domains and the clinical parameters (nausea/vomiting, anorexia, diarrhea, fever, peripheral neuropathy and performance status) were used as the response and explanatory variables, respectively. In this model, the multi-dimensional and longitudinal aspects of QOL data were taken into account. RESULTS: All four domains were significantly affected by the occurrence of nausea/vomiting, anorexia and diarrhea. No influence of peripheral neuropathy on the domains was detected. Performance status was significantly related to the domains (except the psychosocial domain). CONCLUSION: This study revealed, by examination of multi-dimensional repeated QOL data, that clinical parameters had significant effects on QOL in patients undergoing chemotherapy. Our findings suggest that supportive care to control non-hematological adverse events, especially gastrointestinal, could maintain overall QOL in cancer patients in an earlier phase of chemotherapy.

Individually different "weights" of quality of life assessment in patients with advanced nonsmall-cell lung cancer.

BACKGROUND AND OBJECTIVE: The structure of quality of life (QOL) assessment was investigated by estimating subject-specific as well as population-averaged "weights" for four domains (functional, physical, mental, and psychosocial) relative to global QOL. METHODS: Among 583 eligible patients with advanced nonsmall-cell lung cancer in two phase III trials, 377 completed QOL questionnaires at baseline, and during treatment. A random coefficients model was applied, using the global QOL score and scores for the four domains as response and explanatory variables, respectively. RESULTS: A large diversity in subject-specific weights was found for the physical and psychosocial domains during treatment and for the psychosocial and functional domains after treatment. The population-averaged weights of all domains were significant during treatment (especially the physical domain), as well as after treatment (except the functional domain). CONCLUSION: Thus, all four domains were associated with global QOL, and the associations varied among individual patients as well as among the domains.

Occurrence of bronchioloalveolar cell carcinoma in two brothers: comparison of clinical features and immunohistochemical findings.

It has been suggested that lung cancer sometimes aggregates in families. However, the familial occurrence of bronchioloalveolar carcinoma (BAC) is extremely rare. We present a family in which two brothers had BAC. The clinical features and immunohistochemical findings of BAC in the two brothers were compared. Immunohistochemical findings revealed that both cases of BAC had very similar immunopathological features in epithelial marker expression. A review of the literature revealed that this is the third case of BACs in a single family.

Nonspecific interstitial pneumonia/fibrosis completely recovered by adding cyclophosphamide to corticosteroids.

Nonspecific interstitial pneumonia/fibrosis (NSIP) was first described by Katzenstein and Fiorelli in 1994 (Am J Surg Pathol 18: 136-147). Many reports have described that corticosteroids are effective for NSIP. We describe a case of group II idiopathic NSIP in whom cyclophosphamide was administered since the initial response to corticosteroids had been insufficient. Lung biopsy was performed by video-assisted thoracoscopic surgery and NSIP was diagnosed pathologically, clinically and radiologically. Although the initial response to corticosteroids was insufficient, interstitial infiltrates on chest computed tomography improved dramatically after adding intravenous cyclophosphamide followed by oral cyclophosphamide. This case demonstrates that the addition of cyclophosphamide to corticosteroids might be a useful treatment for patients with NSIP.

Evaluation of the clonality of multilobar bronchioloalveolar carcinoma of the lung: case report.

A case of multilobar bronchioloalveolar carcinoma (BAC) is reported. To investigate the clonality of BAC, immunohistochemical staining as well as genetic analysis were performed. To investigate point mutations of the p53 gene, we used the polymerase chain reaction and fluorescence-based single strand conformation polymorphism analysis method. The BAC tissues of the right upper lobe, right lower lobe, and the other lobes were considered to be multiclonal. This case suggests that multilobar BAC might occur with multiclonality.