A Phase II Study of Irinotecan for Patients with Previously Treated Small-Cell Lung Cancer.

OBJECTIVE: Chemotherapy with irinotecan plus cisplatin has shown promise in chemo-naïve small-cell lung cancer (SCLC) patients. However, irinotecan treatment for relapsed or refractory SCLC has not been adequately evaluated. This phase II study evaluated the appropriate treatment schedule of irinotecan as a single agent. This study was designed to determine the antitumor activity, toxicity, and survival in previously treated SCLC patients. METHODS: Previously treated SCLC patients with at least one platinum-based regimen received irinotecan (100 mg/m2) on days 1 and 8, every 3 weeks, until disease progression. The assessment of the response rate was the primary endpoint. RESULTS: Thirty patients were enrolled, with an objective response rate of 41.3% (95% confidence interval [CI] 25.5-59.3), and a disease control rate of 69%. Median progression-free and overall survival was 4.1 months (95% CI, 2.2-5.4) and 10.4 months (95% CI, 8.1-14), respectively. The grade 3/4 hematological toxicities were neutropenia (36.7%), thrombocytopenia (3.3%), anemia (13.3%), and febrile neutropenia (6.6%). There were no grade 4 nonhematological toxicities. Frequent grade 3 nonhematological toxicities included diarrhea (10%), anorexia (6.6%), and hyponatremia (6.6%). CONCLUSIONS: This phase II study showed a high objective response rate and long survival. Irinotecan monotherapy schedule used was well tolerated, and could be an active treatment option for these patients.

Cytotoxic T cell activity against peptides of Hu protein in anti-Hu syndrome.

Half of all patients with limbic encephalitis and small cell lung carcinoma (SCLC) have anti-Hu antibodies that react with all of central and peripheral nervous system neuronal nuclei in immunohistochemical studies and 35- to 40-kDa reactive bands on western blots of extracts from isolated central nervous system neurons. The roles of anti-Hu antibodies in neuronal damage, however, have yet to be shown. Evidence of infiltration of CD8-positive T cells to tumors and affected nervous tissues and limited use of the T cell receptor repertoire in the central nervous system suggests that CD8-positive cytotoxic T cells (CTL) cause neuronal loss. We found the HLA B7 supertype in all of seven Japanese patients with anti-Hu syndrome. We identified HLA class I-restricted, CD 8-positive cytotoxic T cell activity in peripheral blood from three patients with anti-Hu syndrome for five peptides with binding motifs for the HLA B7 supertype in the amino acid sequence of the Hu protein. This study support the involvement of CD8-positive cytotoxic T cells in the development of paraneoplastic neurological syndrome with anti-Hu antibodies.

[An outbreak of pulmonary tuberculosis probably due to exogenous reinfection at a nursing home for the elderly].

In Japan and other countries where tuberculosis is not so common, people who were once infected with tuberculosis are thought to rarely suffer from the disease again due to exogenous reinfection. We experienced a mass outbreak of tuberculosis with 27 patients (including the source of infection) at a nursing home for the elderly. Epidemiological investigation suggested that the source of infection was an 82-year-old woman resident. For about 2 years before this outbreak, she had complained of a productive cough. At the time of the diagnosis of tuberculosis, chest radiography revealed a cavitary lesion and a smear of her sputum revealed organisms rated as Gaffky No. 8. Sputum culture was also positive (++++). Of the 27 patients, 19 (including the source) underwent restriction fragment length polymorphism (RFLP) analysis of isolates from the sputum. Eighteen patients showed an identical RFLP pattern, indicating that the infection had arisen from one source. Out of all patients, the source case of infection, 9 others with the same RFLP pattern, and other 3 who did not undergo RFLP analysis were admitted to our hospital. In 12 patients (3 men and 9 women excluding the source case) aged 80.6 years (range: 67-89 years), chest radiography disclosed tuberculous lesions, and smears, the polymerase chain reaction, and culture of sputum demonstrated Mycobacterium tuberculosis. As the prevalence of tuberculosis infection in Japanese aged 80 years at the time of the mass outbreak (1995) was presumed to be about 80%, the disease seemed to be caused by exogenous reinfection in most of these patients. All of the patients had senile dementia and other complications, and they were bedridden and undernourished. Anemia, hypoalbuminemia and lymphocytopenia were also observed in most of the cases. Malnutrition due to these complications appeared to be a possible risk factor of tuberculosis caused by exogenous reinfection.