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BACKGROUND: The purpose was to investigate adjuvant marrow-supportive high-dose chemotherapy compared with an equitoxicity-tailored comparator arm. PATIENTS AND METHODS: Five hundred and twenty-five women below the age of 60 years with operated high-risk primary breast cancer were randomised to nine cycles of granulocyte colony-stimulating factor supported and individually tailored FEC (5-fluorouracil, epirubicin, cyclophosphamide), (n = 251) or standard FEC followed by marrow-supported high-dose therapy with CTCb (cyclophosphamide, thiotepa, carboplatin) therapy (n = 274), followed by locoregional radiotherapy and tamoxifen for 5 years. RESULTS: There were 104 breast cancer relapses in the tailored FEC group versus 139 in the CTCb group (double triangular method by Whitehead, P = 0.046), with a median follow-up of all included patients of 60.8 months. The event-free survival demonstrated 121 and 150 events in the tailored FEC- and CTCb group, respectively [P = 0.074, hazard ratio (HR) 0.804, 95% confidence interval (CI) 0.633-1.022]. Ten patients in the tailored FEC regimen developed acute myeloid leukaemia (AML)/myelodysplasia (MDS). One hundred deaths occurred in the tailored FEC group and 121 in the CTCb group (P = 0.287, HR 0.866, 95% CI 0.665-1.129). CONCLUSION: The update of this study shows an improved outcome linked to the tailored FEC treatment in relation to breast cancer relapse, but also an increased incidence of AML/MDS.

AIM OF THE STUDY: To produce an empirical estimate of the nature and magnitude of the error produced by incorrect timing quality of life (QoL) measurements in patients receiving chemotherapy. DESIGN: In a multicentre trial, 283 patients were randomized to receive either docetaxel (T) or sequential methotrexate and 5-fluorouracil (MF). The QoL was assessed at baseline and before each treatment using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30). The study design was retrospective. Data were analysed using t-tests. RESULTS: Erroneous timing affected the QoL findings in both treatment arms. At baseline, there were statistically significant differences in the MF group on the nausea/vomiting scale, with ill-timed assessment showing more symptoms, and in the T group on the physical functioning scale with ill-timed assessments indicating better QoL. The mean scores of correct vs. incorrect timings over the first 14 cycles showed statistically significant differences on several scales. In the MF group, ill-timed assessments indicated significantly worse physical functioning and global QoL, and significantly more of the following symptoms: fatigue, nausea/vomiting, insomnia, appetite loss, and constipation. In the T group, ill-timed assessment showed better physical functioning, less dyspnoea and more insomnia than correctly timed assessments. The reasons for erroneous timing were not always detectable retrospectively. However, in some cases the MF group, being in standard treatment, seemed to have followed a clinical routine not involving the active participation of the study nurse responsible, whereas patients in the experimental T group were more consistently taken care of by the study nurses. CONCLUSIONS: Incorrect timing of QoL assessments in oncological trials jeopardises both the reliability of the QoL findings within treatment and the validity of QoL outcome comparisons between treatments. This issue shou

Working with computer-aided design (CAD) tools is not the optimal way of working during the initial stages of new product development, re-engineering product development or production tool development. This is due to the fact that CAD programs force engineers to build the products up from exactly defined details and not from the totality of the concept down to the details. To save time and money malting creative products the engineers instead should gradually proceed from greater roughness in dimensions and shape towards smaller tolerances and well-defined surfaces as the end result captured in product data management (PDM) format. An ideal engineering pathway from project start to production-ready product is rough sketching (pencil-aided design-PAD), rough physical modeling (model aided design-MAD) before different computer-aided engineering (CAE) tools are finally used.

This paper describes some of the complex relationships that exist between R&D (research and development) and M&S (marketing and sales). Factors impacting R&D and M&S are analysed such as company size, company age, wishes for changes in the individual company, etc. Seven propositions are presented. One specific finding from the study is that, for different product life cycles (PLCs), R&D and M&S often counteract so that when R&D spendings are allowed to increase, M&S spendings are reduced and vice versa. Management of technology (MoT) is not an exact science, and therefore the paper focuses on magnitudes of order instead of decimals in R&D and M&S expenditures for individual companies depending on branch, and differing situations. One important result of the investigation is that short PLCs means larger R&D spendings, and vice versa. (C) 1998 Elsevier Science Ltd. All rights reserved.

For enterprises which are growing, developing products or facing tough competition, cash flow is often a limiting factor which determines their success or failure. This article is based on action research in a small enterprise with liquidity shortage whose sales grew at a rare of 20% while R&D amounted to 15% and profits to 8% of turnover From the investigation it appeared that the most important managing/financial activity consisted of weekly cash flow planning with frequent feedback Discrepancies between estimates and outcomes suggested what action was to be taken. Some benefits of continuous liquidity planning include better knowledge of revenue and expenses, better total quality, greater personnel involvement, better liquidity, smaller inventory, better earning capacity, and so forth. In the article a model for continuous liquidity planning is presented based on the study's findings. (C) 1997 Elsevier Science Ltd.

This article brings hands-on knowledge from the integrated development process of a new advanced product that had to be launched on to the market in an extremely short time. Quick, effective development was accomplished through product reviewing or benchmarking, user and subcontractor involvement, dynamic and parallel activities, active, motivating leadership and consensus among those involved. The development process proved to be a winding journey with many problems to be overcome in a flexible and innovative way. No breaks were allowed and formal board meetings, stage-gate and other bureaucratic systems were avoided. Thorough cash-flow analyses were continuously carried out. The hectic pace created problems for and tension in the company seen from both short and long perspectives. Theoretical models of integrated product development did not match well to reality which is why the new concept, dynamic product development, is launched here. The article is based on participating action research.