Peritoneal carcinomatosis immunotherapy with the trifunctional anti-EpCAM x anti-CD3 antibody catumaxomab in patients with colon, gastric, or pancreatic cancer: Long-term results after a 2-year follow-up

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 3033-3033
Author(s):  
M. Ströhlein ◽  
F. Lordick ◽  
D. Rüttinger ◽  
O. Schemanski ◽  
M. Jaeger ◽  
...  
Keyword(s):  
Peritoneal Carcinomatosis ◽  
Tumor Cells ◽  
Peritoneal Lavage ◽  
Skin Toxicity ◽  
Complete Response ◽  
Maximum Tolerated Dose ◽  
Long Term Results ◽  
Matched Pair ◽  
Matched Pair Analysis ◽  
Gi Cancer

3033 Background: Peritoneal carcinomatosis (PC) from gastrointestinal (GI) cancer is associated with a poor outcome. The trifunctional antibody catumaxomab may induce remission by redirecting T-lymphocytes and Fcγ-receptor I/III positive accessory cells to tumor cells. The aim of this study was to investigate the treatment of PC with intraperitoneal catumaxomab. Methods: Patients with epithelial cell adhesion molecule (EpCAM)-positive PC from GI cancer were enrolled in a multicenter phase I study and received four sequential intraperitoneal catumaxomab infusions on days 0, 3, 7, and 10 at increasing doses. Results: Twenty-four patients were enrolled. The maximum tolerated dose (MTD) was reached at 10, 20, 50, and 200 μg on days 0, 3, 7, and 10, respectively. The most common drug-related adverse events at the MTD were fever, vomiting, abdominal pain, skin toxicity, and nausea. Eleven of 17 evaluable patients (65%) were progression-free at final examination: one patient had a complete response and three patients had a partial response. EpCAM-positive cells in peritoneal lavage samples decreased in six of 10 evaluable patients. Patient survival was compared in a post hoc matched-pair analysis with PC patients treated with conventional intravenous chemotherapy. Median survival from the time of diagnosis of PC was 502 days in study patients versus 180 days in control patients (log-rank p = .0083). Conclusions: Intraperitoneal treatment with catumaxomab had an acceptable safety profile. Elimination of tumor cells from peritoneal lavage samples, delayed disease progression, and prolonged survival indicate that intraperitoneal catumaxomab is a promising option for the treatment of PC from GI cancer. [Table: see text]

Efficacy of intraperitoneal treatment with the trifunctional antibody catumaxomab in patients with GI-tract cancer and peritoneal carcinomatosis: A matched-pair analysis

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 2544-2544 ◽  
Author(s):  
M. A. Stroehlein ◽  
K. U. Gruetzner ◽  
A. Tarabichi ◽  
K. W. Jauch ◽  
K. Bartelheim ◽  
...  
Keyword(s):  
Peritoneal Carcinomatosis ◽  
Tumor Cells ◽  
Matched Pair ◽  
Control Group ◽  
Advanced Tumor Stage ◽  
Gi Tract ◽  
Tract Cancer ◽  
Matched Pair Analysis ◽  
Intraperitoneal Treatment ◽  
Pair Analysis

2544 Background: Peritoneal carcinomatosis (PC) due to GI-tract cancer is an advanced tumor stage with poor survival. At present, no standard therapy has been recommended, as chemotherapy and surgery showed only limited efficacy in affected patients. When applied intraperitoneally (i.p.), the trifunctional antibody catumaxomab could be shown to destroy intraperitoneal tumor cells in patients with malignant ascites due to ovarian cancer. While binding simultaneously to EpCAM (on tumor cells), CD3 (T cells) and, via the Fc region, to Fc gamma receptor 1 and 3 on accessory cells, it induces a complex immunoreaction against epithelial tumor cells. The aim of this study was to investigate clinical efficacy of i.p. catumaxomab therapy in patients with PC compared to a matched control group. Methods: Between 2003 and 2005, 22 patients with PC due to cancer of colon (n=10), stomach (8), pancreas (3) and CUP (1) received treatment with catumaxomab within a phase I study. Treatment consisted of 3 to 4 i.p. applications (10–200 μg) of escalating catumaxomab doses. The survival was compared with patients receiving conventional therapies in a matched-pair analysis regarding sex, age, tumor surgery, chemotherapy, and extent of PC. Patients with existing ileus and clinically significant ascites were not included. Results: Follow up of patients receiving catumaxomab showed a median survival of 12.2 months (range 2–34) after first diagnosis of peritoneal carcinomatosis vs. 9.7 months (range 1–40) in patients with conventional treatment (p=0.005; log-rank). These data will be updated at presentation. Conclusion: Intraperitoneal treatment with the trifunctional antibody catumaxomab may be an attractive option for treatment of patients with peritoneal carcinomatosis due to GI-tract cancer. The convincing results have to be further investigated in clinical phase II/III trials. [Table: see text]

Clinical and Pharmacokinetic Phase I Study of Multitargeted Antifolate (LY231514) in Combination With Cisplatin

1999 ◽  
Vol 17 (10) ◽  
pp. 3009-3016 ◽  
Author(s):  
R. Thödtmann ◽  
H. Depenbrock ◽  
H. Dumez ◽  
J. Blatter ◽  
R. D. Johnson ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Head And Neck Carcinoma ◽  
Skin Toxicity ◽  
Complete Response ◽  
Maximum Tolerated Dose ◽  
Neutropenic Sepsis ◽  
Phase Ii Studies ◽  
Neck Carcinoma ◽  
Further Development ◽  
Cisplatin Therapy

PURPOSE: Multitargeted antifolate (MTA; LY231514) has broad preclinical antitumor activity and inhibits a variety of intracellular enzymes involved in the folate pathways. This study was designed to (1) determine the maximum-tolerated dose (MTD), dose-limiting toxicities (DLT), and pharmacokinetics of MTA combined with cisplatin; (2) determine a recommended dose for phase II studies; and (3) collect anecdotal information on the antitumor activity of MTA combined with cisplatin. PATIENTS AND METHODS: Patients with solid tumors received MTA intravenously over 10 minutes and cisplatin over 2 hours once every 21 days. In cohort 1, both agents were administered on day 1 starting with MTA 300 mg/m2 and cisplatin 60 mg/m2. In cohort 2, MTA (500 or 600 mg/m2) was administered on day 1, followed by cisplatin (75 mg/m2) on day 2. RESULTS: In cohort 1, 40 assessable patients received 159 courses of treatment. The MTD was MTA 600 mg/m2/cisplatin 100 mg/m2. DLTs were reversible leukopenia/neutropenia and delayed fatigue. Hydration before cisplatin therapy did not influence MTA pharmacokinetics. Eleven objective remissions included one complete response in a patient with relapsed squamous cell head and neck carcinoma, and partial responses in four of ten patients with epithelial pleural mesothelioma. In cohort 2, 11 assessable patients received 23 courses of treatment. The MTD was MTA 600 mg/m2 and cisplatin 75 mg/m2. DLTs were neutropenic sepsis, diarrhea, and skin toxicity. Two patients died of treatment-related complications during the study. Two patients had objective remissions (one mesothelioma patient, one colon cancer patient). CONCLUSION: The combination of MTA and cisplatin is clinically active, and administering both agents on day 1 is superior to a split schedule. Further development of this combination for mesothelioma is warranted.

A matched pair analysis of intra- and postoperative catumaxomab in patients with ovarian cancer from a multicenter, single-arm phase II trial versus a consecutive single-center collective of ovarian cancer patients without immunotherapy.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 5080-5080 ◽  
Author(s):  
Klaus Pietzner ◽  
Radoslav Chekerov ◽  
Alexander Reinthaller ◽  
Daniel Reimer ◽  
Toralf Reimer ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Adjuvant Chemotherapy ◽  
Cancer Patients ◽  
Tumor Cells ◽  
Cytoreductive Surgery ◽  
Matched Pair ◽  
Control Group ◽  
Matched Pair Analysis ◽  
Matching Criteria ◽  
Pair Analysis

5080 Background: Advanced ovarian cancer is still connected to high mortality rates due to intraperitoneal tumor cells that survive radical cytoreductive surgery as well as adjuvant chemotherapy. These persistent tumor cells need to be targeted in order to improve survival. Catumaxomab has demonstrated the ability to kill EpCAM-positive intraperitoneal tumor cells of ovarian cancer patients in studies aiming to controll malignant ascites in the recurrent setting. This analysis was conducted to investigate the efficacy of intraperitoneal catumaxomab at the timepoint of primary cytoreductive surgery and postoperative period, prior to standard adjuvant chemotherapy. Methods: Ovarian cancer patients undergoing radical surgery received one intraoperative (10 μg) followed by four subsequent intraperitoneal (i.p.) dosages (10, 20, 50 and 150 μg) of catumaxomab on days 7, 10, 13, and 16, respectively. Because of the single arm design of the study, the patients treated with catumaxomab were compared in a matched pair analysis to consecutive patients with primary ovarian cancer who received standard treatment without catumaxomab in a large center, in order to compare survival. The two main prognostic factors of stage and level of tumorreduction were chosen as matching criteria. Results: Of 58 patients screened, 41 were treated with catumaxomab and available for survival evaluation. Median age was 57 years in the catumaxomab group and 59 years in the matched-pair control group. The most comon histology was the serous subtype with 70.7 % in the catumaxomab and 80.5 % of the patients in the control group. The median for overall survival was reached for the historical consecutive matched-pair control collective, but is not yet reached for the catumaxomab group. However, 3-year survival data were available for both groups and showed survival of 85.4% (35) in the catumaxomab group and 63.4% (26) in the matched-pair control group (p-value: 0.041; HR 2.073) Conclusions: There seems to be a trend to beneficial 3-year survival in the catumaxomab group, suggesting that a phase III trial is warranted.

scholarly journals A comparison between Asians and Caucasians in the dimensions of the femoral isthmus based on a 3D-CT analysis of 1189 adult femurs

2021 ◽  
Author(s):  
Darius M. Thiesen ◽  
Dimitris Ntalos ◽  
Alexander Korthaus ◽  
Andreas Petersik ◽  
Karl-Heinz Frosch ◽  
...  
Keyword(s):  
Proximal Femur ◽  
Strong Predictor ◽  
Matched Pair ◽  
3D Ct ◽  
Femur Fractures ◽  
Matched Pair Analysis ◽  
Significant Difference ◽  
Ct Analysis ◽  
Ct Data ◽  
The Individual

Abstract Introduction For successful intramedullary implant placement at the femur, such as nailing in unstable proximal femur fractures, the use of an implant that at least reaches or exceeds the femoral isthmus and yields sufficient thickness is recommended. A number of complications after intramedullary femoral nailing have been reported, particularly in Asians. To understand the anatomical features of the proximal femur and their ethnic differences, we aimed to accurately calculate the femoral isthmus dimensions and proximal distance of Asians and Caucasians. Methods In total, 1189 Asian and Caucasian segmented 3D CT data sets of femurs were analyzed. The individual femoral isthmus diameter was precisely computed to investigate whether gender, femur length, age, ethnicity or body mass index have an influence on isthmus diameters. Results The mean isthmus diameter of all femurs was 10.71 ± 2.2 mm. A significantly larger diameter was found in Asians when compared to Caucasians (p < 0.001). Age was a strong predictor of the isthmus diameter variability in females (p < 0.001, adjusted r2 = 0.299). With every year of life, the isthmus showed a widening of 0.08 mm in women. A Matched Pair Analysis of 150 female femurs showed a significant difference between isthmus diameter in Asian and Caucasian femurs (p = 0.05). In 50% of the cases the isthmus was found in a range of 2.4 cm between 16.9 and 19.3 cm distal to the tip of the greater trochanter. The female Asian femur differs from Caucasians as it is wider at the isthmus. Conclusions In absolute values, the proximal isthmus distance did not show much variation but is more proximal in Asians. The detailed data presented may be helpful in the development of future implant designs. The length and thickness of future standard implants may be considered based on the findings.

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