Yoko Kida

Amrubicin at a lower-dose with routine prophylactic use of granulocyte-colony stimulating factor for relapsed small-cell lung cancer

BACKGROUND Recent reports have suggested the efficacy of amrubicin (AMR) for relapsed small-cell lung cancer (SCLC). However, doses of AMR in these reports were 40 mg/m(2) or 45 mg/m(2), and severe and frequent myelosuppression were observed. Such side effects are occasionally intolerable, as serious myelosuppression may induce fatal infections. To overcome this clinical problem, we investigated whether 35 mg/m(2) of AMR administration with routine prophylactic use of granulocyte-colony stimulating factor (G-CSF) can reduce myelosuppression, while maintaining efficacy. METHODS Between July 2003 and November 2008, 30 relapsed SCLC patients receiving 35 mg/m(2)/day of AMR were evaluated. Amrubicin was administered on days 1-3 every 3 or 4 weeks. Routine prophylactic use of G-CSF was performed beginning on day 8 and continuing for at least 5 consecutive days or until neutrophils recovered to the normal level. RESULTS The median number of treatment cycles was four (range 1-9). No complete responses and 13 partial responses were observed, with response rates of: overall 43% (95% confidence interval [CI]: 26-63%); sensitive cases 33% (95% CI: 10-65%); and refractory cases 50% (95% CI: 26-74%) (p=0.4651). The disease control rate (partial response and stable disease) was 80% (95% CI: 61-92%). The progression-free survival times were: overall 4.2 months (95% CI: 3.2-5.2 months); sensitive cases 4.7 months (95% CI: 2.6-5.4 months); and refractory cases 3.5 months (95% CI: 2.6-5.2 months) (p=0.7124). The median OS times were: overall 9.6 months (95% CI: 7.2-12.5 months); sensitive cases 8.4 months (95% CI: 4.6-13.4 months); and refractory cases 11.0 months (95% CI: 6.5-12.6 months) (p=0.9315). The 1-year survival rate was 33%. Regarding grade 3/4 hematological toxicities: leukopenia (47%); neutropenia (50%); anemia (30%); and thrombocytopenia (33%) were observed. Febrile neutropenia occurred in three patients (10%). Transfusions of red blood cells and platelets were performed for eight (27%) and one (3%) patients, respectively. Treatment-related deaths and grade 3/4 non-hematological toxicities were not observed at all. CONCLUSIONS Considering both safety and efficacy, AMR at a dose of 35 mg/m(2) with routine prophylactic use of G-CSF may be more desirable for the treatment of relapsed SCLC in clinical practice.

Combined pulmonary fibrosis and emphysema: effect of pulmonary rehabilitation in comparison with chronic obstructive pulmonary disease

Objective To evaluate the effectiveness of short-term comprehensive inpatient pulmonary rehabilitation for patients with combined pulmonary fibrosis and emphysema (CPFE), and to compare responses with those of patients with chronic obstructive pulmonary disease (COPD) who underwent an identical programme. Design Retrospective analysis of several outcome measures. Setting Pulmonary ward at a 358-bed community teaching hospital. Methods 3-week inpatient pulmonary rehabilitation programme assessed by pulmonary function tests, 6 min walk test and health-related quality of life (HRQL) using the Short Form-36 (SF-36). Results 17 patients with CPFE and 49 patients with COPD were referred to and completed the programme between March 2007 and February 2015. Age, sex, smoking status, body mass index and the Medical Research Council dyspnoea grade were comparable between groups. In the CPFE group, improvement from the start of the programme to the programme end was observed in forced expiratory volume in 1 s (FEV1) (from 1.7±0.4 to 1.8±0.4, p=0.034); however, there was no significant improvement in the 6 min walk test (distance, SpO2 nadir and Borg scale on exercise). With regard to HRQL, improvement was observed in physical function (p=0.015) whereas deterioration was observed in social functioning (p=0.044). In the COPD group, significant improvement was observed after the programme in the FEV1, 6 min walk test and 4 of the 8 SF-36 subscales. There was a significant difference in changes in the 6 min walk distance: −16.6±58.4 in CPFE versus 30.2±55.6 in COPD (p=0.009). In 2 domains, there was a significant difference in SF-36 scores between groups: Δvitality, −6.3±22.4 in CPFE versus 11.3±21.1 in COPD, p=0.009; and Δsocial functioning, −18.8±34.2 in CPFE versus 5.3±35.9 in COPD, p=0.027. Conclusion Patients with COPD derived greater benefits than those with CPFE, from the relatively short periods of inpatient pulmonary rehabilitation.

Therapeutic Effect of Direct Hemoperfusion with a Polymyxin B-Immobilized Fiber Column in the Treatment of HIV-Negative Severe Pneumocystis Pneumonia

Background: Direct hemoperfusion with a polymyxin B-immobilized fiber column (PMX-DHP) has been shown to improve oxygenation in cases of diffuse alveolar damage, but little is known about its effectiveness in treating pneumocystis pneumonia (PCP) in HIV-negative immunosuppressed patients. Objectives: This study was aimed at investigating the effect of PMX-DHP in treating non-HIV-related PCP. Methods: Between October 2005 and September 2008, 6 patients with non-HIV-related PCP were treated with 2 sessions of PMX-DHP at an attending physician’s discretion when severe hypoxemia developed despite conventional treatments including high-dose corticosteroid, whereas 9 patients in a similar condition were treated without PMX-DHP. Changes in oxygenation and radiographic findings in the PMX-DHP group and adverse events associated with PMX-DHP were investigated retrospectively, as were the outcomes for both treatment groups. Results: There was an improvement in PaO2/FiO2 during each PMX-DHP session, from 148.8 ± 52.5 to 188.2 ± 79.3 mm Hg (p = 0.02). After 2 sessions of PMX-DHP, an improvement in PaO2/FiO2, from 131.8 ± 37.4 to 213.3 ± 87.3 mm Hg, was observed (p = 0.04), but no significantly different improvement was detected on the following day. The radiographic findings improved in 4 patients during PMX-DHP. The in-hospital mortality was similarly high in both groups (50% in the PMX-DHP group vs. 67% in the non-PMX-DHP group). No significant adverse events associated with PMX-DHP were observed except for advanced thrombocytopenia in 1 patient. Conclusion: PMX-DHP may serve as an adjunct in the treatment of non-HIV-related PCP, temporarily alleviating severe hypoxemia even in cases refractory to conventional treatments.