Phase I/II trial of weekly cisplatin,etoposide, and irinotecan chemotherapy for metastatic lung cancer: JCOG 9507

Combinations of cisplatin-irinotecan and cisplatin-etoposide are active and well tolerated in patients with both small-cell lung cancer (SCLC) and nonsmall-cell lung cancer (NSCLC). To define the recommended dose for phase II trials of irinotecan combined with cisplatin and etoposide in chemonaive patients with stage IV disease, 56 patients (11 having SCLC and 45 NSCLC) received cisplatin 25 mg m(-2) weekly for 9 weeks, etoposide 60 mg m(-2) for 3 days on weeks 1, 3, 5, 7 and 9, and irinotecan 20-100 mg m(-2) (levels 1-8) on weeks 2, 4, 6 and 8, together with a prophylactical granulocyte colony-stimulating factor support (50 microg m(-2) on days 4-7 on weeks 1, 3, 5, 7 and 9, and on days 2-7 on weeks 2, 4, 6 and 8). Grade 3-4 leukocytopenia, neutropenia and thrombocytopenia were noted in 20 (36%), 28 (50%) and nine (16%) patients, respectively. Grade 3 diarrhoea, grade 3 cardiac toxicity, and grade 4 transaminase elevation developed in one (1.8%) patient each. Totally, four of 56 patients were removed from the study because of toxicity and recovered, and two other patients died in situations where drug toxicity might contribute to their death. Dose-limiting toxicity was noted in less than one-third of patients at dose levels 1-7, but in all patients at dose level 8. Thus, the recommended dose was determined to be level 7 (irinotecan 90 mg m(-2)). The response rates for SCLC and NSCLC were 91% (10/11) and 38% (17/45), respectively. The median survival time and 1-year survival rate were 11.9 months and 46% for SCLC and 10.1 months and 40% for NSCLC, respectively. This regimen was considered to be feasible and promising for the treatment of stage IV SCLC and NSCLC.     

Weekly gemcitabine and cisplatin in advanced non-small-cell lung cancer: A phase II study

Background: The combination of gemcitabine and cisplatin has proven effective in the treatment of advanced non-small-cell lung cancer (NSCLC). However, the optimal schedule for administration of the two drugs has not yet been determined. In this study we evaluated the activity and toxicity of a weekly gemcitabine and cisplatin schedule.Patients and methods: Thirty-six untreated patients with stage IIIB–IV NSCLC entered the study. Treatment consisted of gemcitabine 1000 mg/m2 i.v. and cisplatin 35 mg/m2 i.v., both given weekly on days 1, 8, and 15, followed by one week of rest.Results: Ninety-seven courses (273 weekly administrations) were delivered. The median dose-intensity was 612 mg/m2 per week for gemcitabine (82%) and 21 mg/m2 per week for cisplatin (80%). All 36 of the patients were evaluable for toxicity, and 30 for response. Partial remissions were observed in 12 patients, for an overall response rate of 40% (95% confidence interval (95% CI): 22.5%–57.5%). Most of the partial remissions were seen in IIIB patients (54% of the stage IIIB and 22% of the stage IV patients responded). According to the intent-to-treat principle, the response rate was 33.3% (12 of 36 patients). The median response duration was 9.9 months (range 4–23) and the median survival time 11.8 months (range 1–24). World Health Organization (WHO) grade 3–4 myelotoxicity was: thrombocytopenia in nine patients (25%), neutropenia in six (16.6%) and anemia in six (16.6%); there was very little additional major toxicity.Conclusions: This regimen appears to be active and to have a favourable toxicity profile.     

Estimated sleep debt and work stress in Japanese white-collar workers.

Sleep debt on weekdays in Japanese white-collar workers, estimated using a questionnaire, was associated with age, overtime, and self-rated workload.     

师生对实习周记看法的调查

目的 了解带教老师与实习护生对实习周记的看法．方法 采用问卷调查法调查带教老师与实习护生各100人。结果 大多数师生赞成写周记；师生对周记的内容存在一定的分歧；约半数的师生对周记反映其内心世界持怀疑态度；83％的老师希望周记由病区护士长审阅，而72％的护生则主张由护理部审阅。结论 为了护生能积累知识，引导其正确书写周记或日记；周记与日记一样．应作为隐私而受到他人的尊重与保护；加强师生间的沟通，建立良好的师生感情；管理者可以通过对师生分别进行座谈、交谈、问卷调查、提问、考试等方法了解实习质量与效果。     

多西紫杉醇联合奥沙利铂每周疗法治疗30例高龄晚期胃癌的临床观察

目的观察多西他赛（DOC）联合奥沙利铂（OXA）周剂量方案一线治疗高龄晚期胃癌的临床疗效及不良反应。方法对30例晚期胃癌患者,采用DOC 35mg/m^2,静脉滴注d1,d8;OXA 70 mg/m^2,静脉滴注d1,d8;21d为1周期,至少2个周期后评价疗效。结果26例可评价疗效,按RECIST标准评价近期疗效和不良反应,以CR＋PR为有效,其中CR 4例,PR 14例,SD 6例,PD 2例,RR 69.23%,中位疾病进展时间为5.8个月,中位生存期11.8个月。不良反应主要是骨髓抑制,外周神经炎和胃肠道反应,均为可逆性。本组无治疗相关性死亡。结论多西他赛联合奥沙利铂每周疗法治疗晚期胃癌疗效确切,不良反应轻,患者耐受性好,值得临床推广。     

Long Working Hours and Sleep Disturbances: The Whitehall II Prospective Cohort Study

Study Objective:

To examine whether exposure to long working hours predicts various forms of sleep disturbance; short sleep, difficulty falling asleep, frequent waking, early waking and waking without feeling refreshed.

Design:

Prospective study with 2 measurements of working hours (phase 3, 1991–1994 and phase 5, 1997–1999) and 2 measurements of subjective sleep disturbances (phase 5 and phase 7, 2002–2004).

Setting:

The Whitehall II study of British civil servants.

Participants:

Full time workers free of sleep disturbances at phase 5 and employed at phases 5 and 7 (n = 937–1594) or at phases 3, 5, and 7 (n = 886–1510).

Measurements and Results:

Working more than 55 hours a week, compared with working 35–40 hours a week, was related to incident sleep disturbances; demographics-adjusted odds ratio (95% CI) 1.98 (1.05, 3.76) for shortened sleeping hours, 3.68 (1.58, 8.58) for difficulty falling asleep; and 1.98 (1.04, 3.77) for waking without feeling refreshed. Repeat exposure to long working hours was associated with odds ratio 3.24 (1.45, 7.27) for shortened sleep, 6.66 (2.64, 16.83) for difficulty falling asleep, and 2.23 (1.16, 4.31) for early morning awakenings. Some associations were attenuated after adjustment for other risk factors. To a great extent, similar results were obtained using working hours as a continuous variable. Imputation of missing values supported the findings on shortened sleep and difficulty in falling asleep.

Conclusion:

Working long hours appears to be a risk factor for the development of shortened sleeping hours and difficulty falling asleep.

Citation:

Virtanen M; Ferrie JE; Vahtera J; Elovainio M; Singh-Manoux A; Marmot MG; Kivimäki M. Long working hours and sleep disturbances: the whitehall II prospective cohort study. SLEEP 2009;32(6):737–745.     

奈达铂每周方案同期适形放疗治疗局部晚期鼻咽癌的临床研究

目的:探讨周剂量奈达铂化疗同步适形放疗治疗局部晚期鼻咽癌的疗效及不良反应。方法:81例局部晚期鼻咽癌患者,随机分为奈达铂同期适形放疗组(CRT组)和单纯适形放疗组(RT组)。RT组患者仅行适形放疗,CRT组患者在适形放疗的基础上加用奈达铂。观察两组患者的近期疗效、远期疗效和不良反应。结果:鼻咽部肿块残存率:CRT组为12.2%(5/41),RT组为20.0%(8/40);颈部肿块残存率:CRT组为17.1%(7/41),RT组为37.5%(15/40),CRT组明显低于RT组(P<0.05);CRT组和RT组1、3年生存率分别为92.7%(38/41)、75.6%(31/41)和92.5%(37/40)、70.0%(28/40)(P>0.05)。不良反应主要表现为白细胞减少和Ⅲ度口腔黏膜反应。结论:小剂量奈达铂每周化疗同步放疗可提高局部晚期鼻咽癌颈淋巴消除率,其不良反应可接受。     

Three decades of continuous wrist‐activity recording: analysis of sleep duration

Motor activity recording by a wrist‐worn device is a common method to monitor the rest–activity cycle. The first author wore an actimeter continuously for more than three decades, starting in 1982 at the age of 43.5 years. Until November 2006 analysis was performed on a 15‐min time base, and subsequently on a 2‐min time base. The timing of night‐time sleep was determined from the cessation and re‐occurrence of daytime‐level activity. Sleep duration declined from an initial 6.8 to 6 h in 2004. The declining trend was reversed upon retirement, whereas the variance of sleep duration declined throughout the recording period. Before retirement, a dominant 7‐day rhythm of sleep duration as well as an annual periodicity was revealed by spectral analysis. These variations were attenuated or vanished during the years after retirement. We demonstrate the feasibility of continuous long‐term motor activity recordings to study age‐related variations of the rest–activity cycle. Here we show that the embeddedness in a professional environment imparts a temporal structure to sleep duration.