GLORIA

GEOMAR Library Ocean Research Information Access

X

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
  • 1
    Online Resource
    Online Resource
    Catumaxomab: Pharmacodynamic and pharmacokinetic data from phase IIIb CASIMAS study in patients with malignant ascites.
    American Society of Clinical Oncology (ASCO) ; 2012
    In:  Journal of Clinical Oncology Vol. 30, No. 15_suppl ( 2012-05-20), p. e13108-e13108
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 30, No. 15_suppl ( 2012-05-20), p. e13108-e13108
    Abstract: e13108^ Background: Catumaxomab (anti-EpCAM x anti-CD3) is approved in the EU for the i.p. locoregional treatment of malignant ascites (MA). The peritoneal cavity invaded by epithelial tumor cells provides an environment for tumor-specific, EpCAM-targeted catumaxomab immunotherapy. In order to monitor the local and systemic pharmacodynamic/ pharmacokinetic (PD/PK) profile of catumaxomab, plasma and ascites samples from patients in the CASIMAS study were investigated. Methods: Plasma and ascites samples were collected in patients prior, during and after catumaxomab i.p. infusions. Samples were analysed for a) Selected cytokines (IL-2, -4, -6, -8, -10, and -12, IFN-gamma, TNF-alpha, and GM-CSF) in 20 patients, b) catumaxomab drug levels in 31 patients (14 patients with MA who received all 4 infusions of 10, 20, 50, and 150 µg were evaluable for systemic PK analysis), c) number of EpCAM+ tumor cells in ascites in 11 patients. Results: Drug levels were highest in ascites fluid ranging from 0 to 219.4 ng/mL at day 10 (n=31/31 patients). Low systemic plasma levels were detected in 7/14 patients (median cmax: 623 pg/mL). In 7/14 subjects no catumaxomab was detected systemically. Furthermore, cytokine concentrations in ascites were higher compared to plasma. Mainly IL-6, -8 & -10 and IFN-gamma were detected; in few cases TNF-alpha and IL-2. Whereas IL-4, -12, and GM-CSF were not detected at all. Anti-tumor activity was proven by i.p. tumor cell elimination. Tumor cell count in ascites dropped markedly below baseline. In the majority (7/11) of patients no EpCAM+ tumor cells were detectable after therapy. Before therapy, in 165/166 evaluable patient samples EpCAM+ tumor cells were detected in the ascites fluid. Conclusions: Catumaxomab represents a locoregional immunological i.p. treatment eliminating tumor cells in the peritoneal cavity and thereby effectively controlling MA. Catumaxomab primarily remains in the peritoneal cavity with low systemic exposure. In line with this, cytokines are mainly released locally, at the site of action. These PD/PK results confirm the results obtained in the pivotal phase II/III study.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/jco.2012.30.15_suppl.e13108
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2012
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 2
    Online Resource
    Online Resource
    Quality of life in patients with malignant ascites during catumaxomab treatment: Results from the CASIMAS trial.
    American Society of Clinical Oncology (ASCO) ; 2012
    In:  Journal of Clinical Oncology Vol. 30, No. 15_suppl ( 2012-05-20), p. e13095-e13095
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 30, No. 15_suppl ( 2012-05-20), p. e13095-e13095
    Abstract: e13095^ Background: Malignant Ascites (MA) is associated with a poor prognosis and limited palliative treatment options. To demonstrate the value of a new treatment the assessment of quality of life (QoL) is of particular importance. Following the demonstration of catumaxomab’s potential to stabilize QoL and prolong the time to first deterioration of QoL, results from CASIMAS give evidence that the QoL of patients remains unaffected during catumaxomab treatment Methods: In a two-arm, open-label, multicentre phase II/III study 219 patients were randomized to catumaxomab plus premedication of 25 mg prednisolone (111 pts) or to catumaxomab alone (108 pts) QoL was measured using the EQ-5D visual analogue scale (EQ-VAS). The EQ-VAS reports the respondent’s self-rated health on a vertical scale where the endpoints are labelled “Best imaginable health state” (100) and “Worst imaginable health state” (0). This information is used as a quantitative measure of health outcome. Patients were asked to complete EQ-VAS during the treatment period (d 0, 3 and 10) and follow-up (d8, 28). Descriptive analyses were performed according to EQ-5D User Guide (Version 4.0). Additionally ascites related symptoms were measured with a disease specific FACIT patient questionnaire. Results: For the pooled population (catumaxomab plus prednisolone and catumaxomab alone) longitudinal analysis of the EQ-VAS showed no relevant changes in mean score during the treatment period of catumaxomab (d0: 51.5; d3: 50.9; d10: 51.0) and compared to screening (52.7). An increase in mean values was observed in the follow-up period (d8: 53.9, d28: 57.1). Descriptive comparison of both treatment groups revealed no major differences in QoL and ascites related symptoms during the treatment and follow-up period, indicating that prednisolone has no impact on patient`s self-rated health. Conclusions: This analysis shows that QoL as measured by EQ-VAS remains unaltered during the treatment with catumaxomab and improves after the treatment period. The improvement is plausible due to the prolonged-puncture-free survival and is consistent with previous observations of QoL changes during and after intraperitoneal treatment with catumaxomab.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/jco.2012.30.15_suppl.e13095
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2012
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 3
    Online Resource
    Online Resource
    Catumaxomab with and without prednisolone in patients with malignant ascites due to epithelial cancer: Results from the phase IIIb CASIMAS study.
    American Society of Clinical Oncology (ASCO) ; 2012
    In:  Journal of Clinical Oncology Vol. 30, No. 15_suppl ( 2012-05-20), p. e13097-e13097
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 30, No. 15_suppl ( 2012-05-20), p. e13097-e13097
    Abstract: e13097^ Background: The primary objective of this study was to compare catumaxomab with prednisolone (CP) to catumaxomab without prednisolone (C) as 3-hour intraperitoneal (i.p.) infusion by demonstrating superiority for safety and non-inferiority for efficacy of the CP arm. Methods: 219 patients were randomized to catumaxomab plus premedication of 25 mg prednisolone (111 pts) or to catumaxomab alone (108 pts). The primary endpoint was the composite safety score (CSS) summarizing the worst CTCAE grades for the main TEAEs (pyrexia, nausea, vomiting, and abdominal pain). A potential impact of prednisolone on efficacy was assessed by the co-primary endpoint puncture-free survival (PuFS). Further parameters included overall survival (OS) and time to next therapeutic puncture (TTPu). Results: The superiority of CP for safety was not proven as the mean CSS was comparable in the two groups (CP: 4.1; C: 3.8 for; p= 0.383). The median PuFS was slightly lower in CP (30 days) compared to C (37 days). However the hazard ratio (HR) for PuFS (HR: 1.130, p=0.402) as well as the 75% quartiles (CP: 155 days, C: 92 days) were in favour of CP compared to C. The median TTPu was similar in both groups (CP: 78 days; C: 102 days, p= 0.599). The majority of patients (123 pts) had no therapeutic paracentesis prior to death (CP: 54.8%; C; 61.7%, p=0.297). Median OS was longer for CP (CP: 124 days; C: 86 days, p= 0.186) without statistical significance. Conclusions: The CASIMAS results are in concordance with the data of the pivotal study and thus confirm the robustness of the treatment effect of catumaxomab in malignant ascites. The administration of 25mg prednisolone as premedication prior to catumaxomab infusion did not change the safety profile and did not negatively impact the efficacy of catumaxomab. The composite safety score after 3-hour infusion time was comparable to that seen in the pivotal study using 6 hours.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/jco.2012.30.15_suppl.e13097
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2012
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...