Systemtherapie des kolorektalen Karzinoms

Zusammenfassung: Die medikamentöse Behandlung des kolorektalen Karzinoms hat in den letzten 10Jahren eindrückliche Fortschritte gemacht. Neben dem altbewährten 5-Fluorouracil stehen heute neue Zytostatika zur Verfügung wie Irinotecan und Oxaliplatin. Monoklonale Antikörper wie Bevacizumab und Cetuximab haben erfolgreich Eingang in aktuelle Therapiestrategien gefunden. Auf der Basis randomisierter klinischer Studien lassen sich heute rationale Therapiestrategien formulieren, wie in diesem Beitrag dargestell

Molekular zielgerichtete Therapie

Zusammenfassung: Bis vor knapp 10Jahren stützte sich die Tumortherapie auf 3Säulen: die Chirurgie, die Strahlentherapie und die zytostatische Chemotherapie. Eine definitive Heilung im Bereich der soliden Tumoren versprach meist nur eine vollständige Entfernung des Tumors durch den Chirurgen. Radiotherapeuten und Onkologen konnten nur einem kleinen Teil ihrer Patienten langfristig helfen. Antikörpertherapien, Antitumorvakzinierungen oder gar genspezifische, individualisierte Therapieformen existierten zwar als Visionen, diese schienen Mitte der 90er-Jahre von einer klinischer Anwendung noch weit entfernt. Mit der Einführung des Antikörpers Rituximab (1997) und des Tyrosinkinaseinhibitors Imatinib (2001) in die klinische Praxis kamen 2 neuartige Substanzen auf den Markt, die Denken und Vorstellungen in der Onkologie grundsätzlich veränderten. Diese Therapeutika ließen aus Visionen Realitäten werden, die der Pharmaindustrie, den Klinikern und Patienten neue Perspektiven bezüglich Machbarkeit und kommender Möglichkeiten im Bereich der Tumortherapie eröffnet haben. Im Folgenden soll ein Überblick über die Entwicklung der 4.Säule der Tumortherapie, der sog. "targeted therapy", gegeben werde

Bipolar HII regions - Morphology and star formation in their vicinity - I - G319.88++00.79 and G010.32−-00.15

Our goal is to identify bipolar HII regions and to understand their morphology, their evolution, and the role they play in the formation of new generations of stars. We use the Spitzer and Herschel Hi-GAL surveys to identify bipolar HII regions. We search for their exciting star(s) and estimate their distances using near-IR data. Dense clumps are detected using Herschel-SPIRE data. MALT90 observations allow us to ascertain their association with the central HII region. We identify Class 0/I YSOs using their Spitzer and Herschel-PACS emissions. These methods will be applied to the entire sample of candidate bipolar HII regions. This paper focuses on two bipolar HII regions, one interesting in terms of its morphology, G319.88$+$00.79, and one in terms of its star formation, G010.32$-$00.15. Their exciting clusters are identified and their photometric distances estimated to be 2.6 kpc and 1.75 kpc, respectively. We suggest that these regions formed in dense and flat structures that contain filaments. They have a central ionized region and ionized lobes perpendicular to the parental cloud. The remains of the parental cloud appear as dense (more than 10^4 per cm^3) and cold (14-17 K) condensations. The dust in the PDR is warm (19-25 K). Dense massive clumps are present around the central ionized region. G010.32-00.14 is especially remarkable because five clumps of several hundred solar masses surround the central HII region; their peak column density is a few 10^23 per cm^2, and the mean density in their central regions reaches several 10^5 per cm^3. Four of them contain at least one massive YSO; these clumps also contain extended green objects and Class II methanol masers. This morphology suggests that the formation of a second generation of massive stars has been triggered by the central bipolar HII region. It occurs in the compressed material of the parental cloud.Comment: 32 pages, 28 figures, to be published in A&

Addition of cetuximab to first-line chemotherapy in patients with advanced non-small-cell lung cancer: a cost-utility analysis

Background: Adding cetuximab to standard chemotherapy results in a moderate increase of overall survival in patients with advanced non-small-cell lung cancer (NSCLC), but the cost-effectiveness is unknown. Materials and methods: A Markov model was constructed based on the results of the First-Line ErbituX in lung cancer randomized trial, adding cetuximab to cisplatin-vinorelbine first-line chemotherapy in patients with advanced NSCLC. The primary outcome was the incremental cost-effectiveness ratio (ICER) of adding cetuximab, expressed as cost per quality-adjusted life year (QALY) gained, and relative to a willingness-to-pay threshold of €60 000/QALY. The impact of cetuximab intermittent dosing schedules on the ICER was also evaluated. Results: Adding cetuximab to standard chemotherapy leads to a gain of 0.07 QALYs per patient at an additional cost of €26 088. The ICER for adding cetuximab to chemotherapy was €376 205 per QALY gained. Intermittent cetuximab dosing schedules resulted in ICERs per QALY gained between €31 300 and €83 100, under the assumption of equal efficacy. Conclusions: From a health economic perspective, the addition of cetuximab to standard first-line chemotherapy in patients with epidermal growth factor receptor-expressing advanced NSCLC cannot be recommended to date, due to a high ICER compared with other health care interventions. Treatment schedules resulting in more favorable cost-utility ratios should be evaluate

Trastuzumab beyond progression: a cost-utility analysis

Background: The continuation of trastuzumab beyond progression in combination with capecitabine as secondary chemotherapy for HER2-positive metastatic breast cancer (MBC) prolongs progression-free survival without a substantial increase in toxicity. Patients and methods: A Markov cohort simulation was used to follow the clinical course of typical patients with MBC. Information on response rates and major adverse effects was derived, and transition probabilities were estimated, based on the results of the Breast International Group 03-05 clinical trial. Direct costs were assessed from the perspective of the Swiss health care system. Results: The addition of trastuzumab to capecitabine is estimated to cost on average an additional of €33 980 and to yield a gain of 0.35 quality-adjusted life years (QALYs), resulting in an incremental cost-effectiveness ratio of €98 329/QALYs gained. Probabilistic sensitivity analysis showed that the willingness-to-pay threshold of €60 000/QALY was reached in 12% of cases. Conclusion: The addition of trastuzumab to capecitabine in MBC patients is more expensive than what is typically regarded as cost-effective but falls within the value ranges found for established regimens in the treatment of MB

NG7538 IRS1 N: modeling a circumstellar maser disk

We present an edge-on Keplerian disk model to explain the main component of the 12.2 and 6.7 GHz methanol maser emission detected toward NGC7538-IRS1 N. The brightness distribution and spectrum of the line of bright masers are successfully modeled with high amplification of background radio continuum emission along velocity coherent paths through a maser disk. The bend seen in the position-velocity diagram is a characteristic signature of differentially rotating disks. For a central mass of 30 solar masses, suggested by other observations, our model fixes the masing disk to have inner and outer radii of about 270 AU and 750 AU.Comment: To appear in The Proceedings of the 2004 European Workshop: "Dense Molecular Gas around Protostars and in Galatic Nuclei", Eds. Y. Hagiwara, W.A. Baan, H.J. van Langevelde, 2004, a special issue of ApSS, Kluwe

The value of PET, CT and in-line PET/CT in patients with gastrointestinal stromal tumours: long-term outcome of treatment with imatinib mesylate

Purpose: Gastrointestinal stromal tumours (GIST) are mesenchymal neoplasms of the gastrointestinal tract that are unresponsive to standard sarcoma chemotherapy. Imaging of GIST patients is done with structural and functional methods such as contrast-enhanced helical computed tomography (ceCT) and positron emission tomography (PET) with 18F-fluorodeoxyglucose (FDG). The aim of this study was to compare the prognostic power of PET and ceCT and to evaluate the clinical role of PET/CT imaging. Methods: All patients with GIST undergoing PET or PET/CT examinations were prospectively included in this study, and the median overall survival, time to progression and treatment duration were documented. The prognostic significance of PET and ceCT criteria of treatment response was assessed and PET/CT was compared with PET and ceCT imaging. Data for 34 patients (19 male, 15 female, 21-76 years) undergoing PET or PET/CT for staging or restaging were analysed. Results: In 28 patients, PET/CT and ceCT were available after introduction of treatment with the tyrosine kinase inhibitor imatinib mesylate (Gleevec; Novartis, Basel, Switzerland). Patients without FDG uptake after the start of treatment had a better prognosis than patients with residual activity. In contrast, ceCT criteria provided insufficient prognostic power. However, more lesions were found on ceCT images than on PET images, and FDG uptake was sometimes very variable. PET/CT delineated active lesions better than did the combination of PET and ceCT imaging. Conclusion: Both PET and PET/CT provide important prognostic information and have an impact on clinical decision-making in GIST patients. PET/CT precisely delineates lesions and thus allows for the correct planning of surgical intervention