Mitoxantrone pleurodesis to palliate malignant pleural effusion secondary to ovarian cancer

BACKGROUND: Advanced ovarian cancer is the leading non-breast gynaecologic cause of malignant pleural effusion. Aim of this study was to assess the efficacy of mitoxantrone sclerotherapy as a palliative treatment of malignant pleural effusions due to ovarian cancer. METHODS: Sixty women with known ovarian cancer and malignant recurrent symptomatic pleural effusion were treated with chest tube drainage followed by intrapleural mitoxantrone sclerotherapy. Survival, complications and response to pleurodesis were recorded. The data are expressed as the mean ± SEM and the median. RESULTS: The mean age of the entire group was 64 ± 11,24 years. The mean interval between diagnosis of ovarian cancer and presentation of the effusion was 10 ± 2,1 months. Eighteen patients (30%) had pleural effusion as the first evidence of recurrence. The mean volume of effusion drained was 1050 ± 105 ml and chest tube was removed within 4 days in 75% of patients. There were no deaths related to the procedure. Side effects of chemical pleurodesis included fever (37–38,5°C) chest pain, nausea and vomiting. At 30 days among 60 treated effusions, there was an 88% overall response rate, including 41 complete responses and 12 partial responses. At 60 days the overall response was 80% (38 complete responses and 10 partial responses). The mean survival of the entire population was 7,5 ± 1,2 months. CONCLUSIONS: Mitoxantrone is effective in the treatment of malignant pleural effusion secondary to ovarian cancer without causing significant local or systemic toxicity

Intrapleural hypotonic cisplatin treatment for malignant pleural effusion in 80 patients with non-small-cell lung cancer: a multi-institutional phase II trial

To assess the effect and toxicity of hypotonic cisplatin treatment (HPT) consisting of the intrapleural administration of cisplatin in distilled water for malignant pleural effusion in patients with non-small-cell lung cancer (NSCLC). Non-small-cell lung cancer patients with cytologically proven and previously untreated malignant pleural effusion were enrolled into this study. Firstly, the lung was fully re-expanded by a tube thoracostomy, and then 25 mg cisplatin in 500 ml of distilled water was instilled through a chest tube and then the tube was clamped. After 1 h, the tube was declamped and allowed to drain. The chest tube was removed when the pleural effusion volume decreased to 200 ml or less per day. A complete response (CR) was considered to occur when the pleural effusion disappeared. A partial response (PR) was determined to occur when the volume of pleural effusion remained under ¼ of hemithorax. The response at 4 weeks was evaluated by an extramural review. Out of 84 patients enrolled from February 1998 to August 2002, 80 patients were eligible and analysed in the present study. The toxicity of HPT was acceptable. Neither a haematological toxicity of any grade nor grade 4 nonhaematological toxicity was observed. Grade 3 nonhaematological toxicities were observed, including nausea (4%), vomiting (3%), pyothorax (1%) and dyspnoea (1%). The median time of drainage from HTP was 4 days. Twenty-seven (34%) and 39 (49%) patients achieved CR and PR, respectively, for an overall response rate of 83% (95% confidence interval, 74–91%). The median duration of the response was 206 days. The median survival time of all patients was 239 days. Hypotonic cisplatin treatment for malignant pleural effusion of NSCLC is therefore considered to be feasible and effective. A phase III study of HPT is thus warranted

Mitomycin C and Vinorelbine for second-line chemotherapy in NSCLC – a phase II trial

Single-agent therapy with Docetaxel or Pemetrexed is the current therapy of choice for second-line treatment in advanced non-small-cell lung cancer (NSCLC). The role of older agents was underattended over the last years. This study presents the combination of Mitomycin C and Vinorelbine in pretreated patients. Forty-two patients (stage IIIB and IV, pretreated with platinum-based chemotherapy) received 8 mg m−2 Mitomycin C on day 1 and 25 mg m−2 Vinorelbine on days 1 and 8 of a 28-day cycle. End points were objective tumour response, survival, and toxicity. Additionally, quality of life (QoL) was assessed. Five patients (11.9 %) achieved partial responses and 13 patients (31.9%) stable disease. Progression-free survival was 16 weeks. The median overall survival was 8.5 month. Eleven patients (26.2 %) suffered from grade 3 or 4 neutropenia and four patients (9.52%) from grade 3 or 4 anaemia. Evaluation of QoL showed that some items ameliorated during therapy. The therapeutic concept including Mitomycin C and Vinorelbine offers an efficacious and well-tolerated regimen, with relatively low toxicity. Objective response and survival data correlate with other second-line studies using different medication. As costs of Mitomycin C and Vinorelbine are lower compared with current drugs of choice, this regimen is likely to be cost-saving

Measurement of the Bottom-Strange Meson Mixing Phase in the Full CDF Data Set

We report a measurement of the bottom-strange meson mixing phase \beta_s using the time evolution of B0_s -> J/\psi (->\mu+\mu-) \phi (-> K+ K-) decays in which the quark-flavor content of the bottom-strange meson is identified at production. This measurement uses the full data set of proton-antiproton collisions at sqrt(s)= 1.96 TeV collected by the Collider Detector experiment at the Fermilab Tevatron, corresponding to 9.6 fb-1 of integrated luminosity. We report confidence regions in the two-dimensional space of \beta_s and the B0_s decay-width difference \Delta\Gamma_s, and measure \beta_s in [-\pi/2, -1.51] U [-0.06, 0.30] U [1.26, \pi/2] at the 68% confidence level, in agreement with the standard model expectation. Assuming the standard model value of \beta_s, we also determine \Delta\Gamma_s = 0.068 +- 0.026 (stat) +- 0.009 (syst) ps-1 and the mean B0_s lifetime, \tau_s = 1.528 +- 0.019 (stat) +- 0.009 (syst) ps, which are consistent and competitive with determinations by other experiments.Comment: 8 pages, 2 figures, Phys. Rev. Lett 109, 171802 (2012

Prognostic value of performance status assessed by patients themselves, nurses, and oncologists in advanced non-small cell lung cancer

Accuracy in the assessment of performance status by oncologists has not been well evaluated. We investigated possible discrepancies in the assessment of performance status among patients, nurses, and oncologists, and evaluated the prognostic importance of each assessment. Two hundred and six inpatients with inoperable, advanced non-small cell lung cancer were investigated prospectively. Weighted Kappa statistics for inter-observer agreement were 0.53 between oncologists and patients and 0.63 between oncologists and nurses. There was a significant difference among the assessments by the three groups (P < 0.001). Oncologists gave the healthiest performance status assessment, nurses an intermediate assessment, and patients the poorest. When included separately in the Cox model, the assessment by each group was significantly correlated with survival. However, the assessment by the patients themselves failed to distinguish survival of patients with performance status 1 and 2. Among the three models including patient-, nurse-, and oncologist-assessed PS, that including oncologist-assessed PS best fitted to the observed survival data. These results showed that the assessment by the patients themselves is different from those by the nurses and the oncologists and provided additional support for the use of the assessment by oncologists in clinical oncology. © 2001 Cancer Research Campaign http://www.bjcancer.co

Adaptive intrapatient dose escalation of cisplatin in combination with low-dose vp16 in patients with nonsmall cell lung cancer

The objective of this phase II and pharmacologic study was to explore the feasibility toxicity and activity of adaptive intrapatient dose escalation of cisplatin in a dose-intensive weekly schedule using predefined levels of exposure, with the ultimate aim to improve the antitumour activity of the therapy in patients with nonsmall cell lung cancer (NSCLC). Platinum DNA-adduct levels in peripheral white blood cells during treatment were used as the primary parameter for adaptive dosing. If DNA-adduct levels were not available, the area under the concentration-time curve (AUC) of unbound platinum in plasma was used for dose adaptation. Target levels for DNA-adducts and AUC have been defined in a previously performed pharmacologic study. The feasibility of adaptive dosing was tested in 76 patients with stage IIIB and IV NSCLC, who were planned to receive 6 weekly courses of cisplatin at a starting dose of 70 mg m-2, together with daily low oral dose of 50 mg VP16. In total, 37 patients (49%) who were given more than one course received a dose increase varying from 10 to 55%. The majority of patients reached the defined target levels by a dose increase during course two. Relevant grade 2 neurotoxicity was observed in eight (10%) patients and reversible ototoxicity grade 2 in 14 (18%) patients. The strategy of adaptive intrapatient dose adjustment of cisplatin is practically feasible in a research setting even when results for dose adaptation have to be reported within a short time-period of I week. The toxicity appeared to be manageable in this cohort of patients. In some patients, exposure after the standard dose was substantially lower than the defined target level and significant dose escalations of more than 50% had to be applied. The response rate (RR) was relatively high: overall 40% (29 out of 72 patients) partial remission (PR), in patients with stage IIIB the RR was 60% (15 out of 25 patients) and with stage IV 30% (14 out of 47 patients). Randomised studies are needed to determine whether the adaptive dosing strategy results in better efficacy than standard dosing

The case for the introduction of new chemotherapy agents in the treatment of advanced non small cell lung cancer in the wake of the findings of The National Institute of Clinical Excellence (NICE)

After years of nihilism towards the use of chemotherapy for non small cell lung cancer in the UK it would appear that we have now reached the point where the use of chemotherapy to relieve symptoms, maintain quality of life, and prolong life, are now accepted for informed patients with good performance status willing to accept short-term toxicities. The use of the new agents vinorelbine, gemcitabine and paclitaxel in combination with cisplatin or carboplatin are all active regimens which offer small but real advantages over standard UK triple therapies (MVP, MIC) in terms of resource use, toxicity profiles and response rates. Overall survival could be increased by as much as 10% at one year on indirect comparisons. The use of docetaxel as second line therapy now offers lung cancer patients a second bite of the cherry, and should overall also prolong survival. It is only in embracing these small gains that we can currently make progress in the treatment of NSCLC

Quality of life data as prognostic indicators of survival in cancer patients: an overview of the literature from 1982 to 2008

<p>Abstract</p> <p>Background</p> <p>Health-related quality of life and survival are two important outcome measures in cancer research and practice. The aim of this paper is to examine the relationship between quality of life data and survival time in cancer patients.</p> <p>Methods</p> <p>A review was undertaken of all the full publications in the English language biomedical journals between 1982 and 2008. The search was limited to cancer, and included the combination of keywords 'quality of life', 'patient reported-outcomes' 'prognostic', 'predictor', 'predictive' and 'survival' that appeared in the titles of the publications. In addition, each study was examined to ensure that it used multivariate analysis. Purely psychological studies were excluded. A manual search was also performed to include additional papers of potential interest.</p> <p>Results</p> <p>A total of 451 citations were identified in this rapid and systematic review of the literature. Of these, 104 citations on the relationship between quality of life and survival were found to be relevant and were further examined. The findings are summarized under different headings: heterogeneous samples of cancer patients, lung cancer, breast cancer, gastro-oesophageal cancers, colorectal cancer, head and neck cancer, melanoma and other cancers. With few exceptions, the findings showed that quality of life data or some aspects of quality of life measures were significant independent predictors of survival duration. Global quality of life, functioning domains and symptom scores - such as appetite loss, fatigue and pain - were the most important indicators, individually or in combination, for predicting survival times in cancer patients after adjusting for one or more demographic and known clinical prognostic factors.</p> <p>Conclusion</p> <p>This review provides evidence for a positive relationship between quality of life data or some quality of life measures and the survival duration of cancer patients. Pre-treatment (baseline) quality of life data appeared to provide the most reliable information for helping clinicians to establish prognostic criteria for treating their cancer patients. It is recommended that future studies should use valid instruments, apply sound methodological approaches and adequate multivariate statistical analyses adjusted for socio-demographic characteristics and known clinical prognostic factors with a satisfactory validation strategy. This strategy is likely to yield more accurate and specific quality of life-related prognostic variables for specific cancers.</p