Phase II study of gemcitabine and vindesine in patients with previously untreated non-resectable non-small-cell lung cancer

Because both vindesine and gemcitabine are active drugs in advanced non-small-cell lung cancer (NSCLC), with different modes of action and only partly overlapping toxicity, a phase II study was performed. Gemcitabine 1000 mg m−2 was given on days 1, 8 and 15 every 4 weeks, while vindesine 3 mg m−2 was administered weekly for 7 weeks, then every 2 weeks. A total of 42 patients with nonresectable NSCLC were included. The median age of patients was 56 years; 57% were men, 52% had adenocarcinoma, 31% squamous cell carcinoma and 17% had large-cell carcinoma. The performance status ranged from 0 to 2 with 83% in performance status 1. The majority (55%) had stage IV disease, while 40% had stage III B and 5% stage III A disease. WHO grade 3–4 leucopenia occurred in five patients (12%) and 9% had grade 4 neutropenia. Thrombocytopenia grade 3–4 was observed in six patients (15%). There were no septic death or bleeding episodes. One patient had a transient WHO grade 4 increase in bilirubin, and four patients had a decrease in glomerular filtration rate below the normal limit; one of these patients developed a non-reversible renal insufficiency. Ten patients (24%) complained of dyspnoea of uncertain mechanism, possibly involving bronchoconstriction. There were one complete and seven partial responses among 40 assessable patients (20%, 95% confidence limits 9–36%). Median response duration was 31 weeks (range 11–83 weeks) and median survival time 31 weeks (range 2–171 weeks). The current combination of gemcitabine and vindesine does not appear to be promising for further examination because of the toxicity and somewhat disappointing activity. © 1999 Cancer Research Campaig

Health information technology: use it well, or don't! Findings from the use of a decision support system for breast cancer management.

The potential of health information technology is hampered by new types of errors which impact is not totally assessed. OncoDoc2 is a decision support system designed to support treatment decisions of multidisciplinary meetings (MDMs) for breast cancer patients. We evaluated how the way the system was used had an impact on MDM decision compliance with clinical practice guidelines. We distinguished "correct navigations" (N+), "incorrect navigations" (N-), and "missing navigations" (N0), according to the quality of data entry when using OncoDoc2. We collected 557 MDM decisions from three hospitals of Paris area (France) where OncoDoc2 was routinely used. We observed 33.9% N+, 36.8% N-, and 29.3% N0. The compliance rate was significantly different according to the quality of navigations, 94.2%, 80.0%, and 90.2% for N+, N-, and N0 respectively. Surprinsingly, it was better not to use the system (N0) than to use it improperly (N-)

Physicians' Attitudes Towards the Advice of a Guideline-Based Decision Support System: A Case Study With OncoDoc2 in the Management of Breast Cancer Patients.

When wrongly used, guideline-based clinical decision support systems (CDSSs) may generate inappropriate propositions that do not match the recommendations provided by clinical practice guidelines (CPGs). The user may decide to comply with or react to the CDSS, and her decision may finally comply or not with CPGs. OncoDoc2 is a guideline-based CDSS for breast cancer management. We collected 394 decisions made by multidisciplinary meeting physicians in three hospitals where the CDSS was evaluated. We observed a global CPG compliance of 86.8% and a global CDSS compliance of 75.4%. Non-CPG compliance was observed in case of a negative reactance to the CDSS, when users did not follow a correct CDSS proposition (8.6% of decisions). Because of errors in patient data entry, OncoDoc2 delivered non-recommended propositions in 21.3% of decisions, leading to compliances with CDSS and CPGs of respectively 21.4% and 65.5%, whereas both compliances exceeded 90% when CDSS advices included CPG recommendations. Automation bias, when users followed an incorrect CDSS proposition explained the remaining non-compliance with CPGs (4.6% of decisions). Securing the use of CDSSs is of major importance to warranty patient safety and benefit of their potential to improve care

Status of potential <it>Pf</it>ATP6 molecular markers for artemisinin resistance in Suriname

<p>Abstract</p> <p>Background</p> <p>Polymorphisms within the <it>PfATP6</it> gene have been indicated as potential molecular markers for artemisinin efficacy. Since 2004, the use of artemisinin combination therapy (ACT) was introduced as first-line treatment of the uncomplicated malaria cases in Suriname. The aim of this research was to determine changes in Suriname in the status of the polymorphic markers in the <it>PfATP6</it> gene before and after the adoption of the ACT-regimen, particularly of the S769N mutation, which was reported to be associated with <it>in vitro</it> Artemether resistance in the neighboring country French Guiana.</p> <p>Methods</p> <p>The <it>PfATP6</it> gene from <it>Plasmodium falciparum</it> parasites in Suriname was investigated in 28 samples using PCR amplification and restriction enzyme analysis, to assess and determine the prevalence of potentially interesting single nucleotide polymorphisms. The polymorphisms [L263E; A623E; S769N], which may be associated with the artemisinin resistant phenotype were characterized in parasites from three endemic regions before and after the adoption of the ACT-regimen. In addition, the status of these molecular markers was compared in paired <it>P. falciparum</it> isolates from patients with recurring malaria after controlled ACT.</p> <p>Results</p> <p>All the investigated samples exhibit the wild-type genotype at all three positions; L263, A623, S769.</p> <p>Conclusion</p> <p>All investigated isolates before and after the adoption of the ACT-regimen and independent of endemic region harbored the wild-type genotype for the three investigated polymorphisms. The study revealed that decreased artemisinin susceptibility could occur independent from <it>PfATP6</it> mutations, challenging the assumption that artemisinin resistance is associated with these mutations in the <it>PfATP6</it> gene.</p

Very Long-Term Complete Remission Can Be Achieved in Men With High-Risk Localized Prostate Cancer and a Very High PSA Value: An Analysis of the GETUG 12 Phase 3 Trial.

Serum prostate specific antigen (PSA) is a well-known prognostic parameter in men with prostate cancer. The treatment of men with very high PSA values and apparently no detectable metastases is not fully established. Ancillary analysis from the GETUG 12 phase 3 trial. Patients with non-metastatic high-risk prostate cancer by bone and computerized tomography (CT) scan were randomly assigned to receive androgen deprivation therapy (ADT) and docetaxel plus estramustine or ADT alone. Relapse-free survival (RFS), clinical RFS, metastases-free survival (MFS), overall survival (OS), and prostate cancer-specific survival (PCSS) were estimated using the Kaplan-Meier method for different levels of PSA (50 ng/mL, 75 ng/mL, and 100 ng/mL). The relationship between PSA and outcomes was studied using residual-based approaches and spline functions. The median follow-up was 12 years (range: 0-15.3). Baseline PSA (&lt;50 ng/mL, n = 328; ≥50ng/mL, n = 85) was associated with improved RFS (P = .0005), cRFS (P = .0024), and MFS (P = .0068). The 12-year RFS rate was 46.33% (CI 40.59-51.86), 33.59% (CI 22.55-44.97), and 11.76% (1.96-31.20) in men with PSA values &lt;50 ng/mL (n = 328), 50-100 ng/mL (n = 68), and ≥100 ng/mL (n = 17), respectively. Exploratory analyses revealed no deviation from the linear relationship assumption between PSA and the log hazard of events. Men with apparently localized prostate cancer and a high baseline PSA value have a reasonable chance of being long-term disease-free when treated with curative intent combining systemic and local therapy

Projet ARGIC: Analyse du retrait-gonflement et de ses incidences sur les constructions. rapport final.

500p