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Donna Niedzwiecki - One of the best experts on this subject based on the ideXlab platform.
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Association Between Results of a Gene Expression Signature Assay and Recurrence-Free Interval in Patients With Stage II Colon Cancer in Cancer and Leukemia Group B 9581 (Alliance).
Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2016Co-Authors: Donna Niedzwiecki, Alan P. Venook, Paula N. Friedman, Wendy L. Frankel, Richard M. Goldberg, Robert J. Mayer, Thomas A. Colacchio, Jude M. Mulligan, Timothy DavisonAbstract:PurposeConventional staging methods are inadequate to identify patients with stage II colon cancer (CC) who are at high risk of recurrence after surgery with curative intent. ColDx is a gene expression, microarray-based assay shown to be independently prognostic for recurrence-free interval (RFI) and overall survival in CC. The objective of this study was to further validate ColDx using formalin-fixed, paraffin-embedded specimens collected as part of the Alliance phase III trial, C9581.Patients and MethodsC9581 evaluated Edrecolomab versus observation in patients with stage II CC and reported no survival benefit. Under an initial case-cohort sampling design, a randomly selected subcohort (RS) comprised 514 patients from 901 eligible patients with available tissue. Forty-nine additional patients with recurrence events were included in the analysis. Final analysis comprised 393 patients: 360 RS (58 events) and 33 non-RS events. Risk status was determined for each patient by ColDx. The Self-Prentice method w...
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Association between ColDx assay result and recurrence-free interval in stage II colon cancer patients on CALGB (Alliance) 9581.
Journal of Clinical Oncology, 2014Co-Authors: Donna Niedzwiecki, Alan P. Venook, Paula N. Friedman, Wendy L. Frankel, Richard M. Goldberg, Robert J. Mayer, Thomas A. Colacchio, Richard D. Kennedy, Timothy DavisonAbstract:455 Background: Only 15-25% of pts with stage II colon cancer (CC) experience recurrence and conventional staging methods neither allow accurate identification of low (L) and high-risk (H) subgroups nor predict benefit of adjuvant chemotherapy. The ColDx assay (Almac Diagnostics) is a 634-probeset gene expression signature shown to be independently prognostic for recurrence-free interval (RFI). The objective of this study was to assess the ability of ColDx to classify stage II CC pts at L- and H-risk of relapse. Methods: This validation study was conducted using formalin fixed paraffin embedded biospecimens and clinical data from CALGB 9581, a phase III trial of Edrecolomab v. observation in pts with normal risk, stage II CC. 1,454 CALGB 9,581 pts met eligibility criteria. A case-cohort sampling design was used to randomly select (RS) 514 pts from 901 eligible pts with available tissue; supplemented by 49 non-RS recurrent pts (total 563). Risk status for each pt was based on a positive or negative ColDx score using a pre-specified cutpoint, 0.4377. The Self Prentice method was used to test the association between ColDx categories and RFI (distant recurrence or death due to primary disease). Results: Initial results in 563 pts were erroneous due to a quality failure in a batch of reagent. 524 samples were re-labeled, re-ordered, and re-assayed using reagents that passed quality control (36 samples had insufficient material; 95 failed ColDx QC). Final analysis comprised 393 pts, 360 RS (58 events; 16%); 33 non-RS events. 216 pts (55%) were predicted H (62 events); 177 (45%) pts were predicted L (29 events). H pts exhibited significantly worse RFI (univariable hazard ratio (HR), 2.0; 95% CI, 1.3-3.3; p < 0.01). ColDx remained significant after adjustment for prognostic factors; HR, 2.1 (95% CI, 1.3-3.4; p < 0.01). Conclusions: The ColDx assay result is associated with RFI in the CALGB 9,581 sub-sample and is independent from other prognostic factors, including MSI. Further investigation is needed to establish the role of this classifier in guiding treatment decisions in this patient population.
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Biologic Determinants of Tumor Recurrence in Stage II Colon Cancer: Validation Study of the 12-Gene Recurrence Score in Cancer and Leukemia Group B (CALGB) 9581
Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2013Co-Authors: Alan P. Venook, Donna Niedzwiecki, Margarita Lopatin, Mark A. Lee, Paula N. Friedman, Wendy L. Frankel, Kim M. Clark-langone, C. Millward, Steven ShakAbstract:Purpose A greater understanding of the biology of tumor recurrence should improve adjuvant treatment decision making. We conducted a validation study of the 12-gene recurrence score (RS), a quantitative assay integrating stromal response and cell cycle gene expression, in tumor specimens from patients enrolled onto Cancer and Leukemia Group B (CALGB) 9581. Patients and Methods CALGB 9581 randomly assigned 1,713 patients with stage II colon cancer to treatment with Edrecolomab or observation and found no survival difference. The analysis reported here included all patients with available tissue and recurrence (n = 162) and a random (approximately 1:3) selection of nonrecurring patients. RS was assessed in 690 formalin-fixed paraffin-embedded tumor samples with quantitative reverse transcriptase polymerase chain reaction by using prespecified genes and a previously validated algorithm. Association of RS and recurrence was analyzed by weighted Cox proportional hazards regression. Results Continuous RS was si...
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documenting the natural history of patients with resected stage ii adenocarcinoma of the colon after random assignment to adjuvant treatment with Edrecolomab or observation results from calgb 9581
Journal of Clinical Oncology, 2011Co-Authors: Donna Niedzwiecki, Monica M Bertagnolli, Robert S Warren, Carolyn C Compton, Nancy E Kemeny, Al B Benson, Gail S Eckhardt, Steven R Alberts, Gity N Porjosh, D J KerrAbstract:Purpose We conducted a randomized trial comparing adjuvant treatment with Edrecolomab versus observation in patients with resected, low-risk, stage II colon cancer. This study also prospectively studied patient- and tumor-specific markers of treatment outcome. Patients and Methods After surgical resection, patients with stage II colon cancer were randomly assigned to either five infusions of Edrecolomab at 28-day intervals or observation without adjuvant therapy. Results Final accrual included 1,738 patients; 865 patients received Edrecolomab, and 873 patients were observed without adjuvant treatment. Median follow-up time was 7.9 years. There were no significant outcome differences between study arms (overall survival [OS], P = .71; disease-free survival, P = .64). The combined 5-year all-cause OS was 0.86 (95% CI, 0.84 to 0.88), and the combined 5-year disease-specific OS was 0.93 (95% CI, 0.91 to 0.94). The relationships between demographic and histopathologic factors and survival differed for all-caus...
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Documenting the Natural History of Patients With Resected Stage II Adenocarcinoma of the Colon After Random Assignment to Adjuvant Treatment With Edrecolomab or Observation: Results From CALGB 9581
Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2011Co-Authors: Donna Niedzwiecki, Monica M Bertagnolli, Robert S Warren, Carolyn C Compton, Nancy E Kemeny, Al B Benson, Steven R Alberts, Gity N Porjosh, S. Gail Eckhardt, D J KerrAbstract:We conducted a randomized trial comparing adjuvant treatment with Edrecolomab versus observation in patients with resected, low-risk, stage II colon cancer. This study also prospectively studied patient- and tumor-specific markers of treatment outcome. After surgical resection, patients with stage II colon cancer were randomly assigned to either five infusions of Edrecolomab at 28-day intervals or observation without adjuvant therapy. Final accrual included 1,738 patients; 865 patients received Edrecolomab, and 873 patients were observed without adjuvant treatment. Median follow-up time was 7.9 years. There were no significant outcome differences between study arms (overall survival [OS], P = .71; disease-free survival, P = .64). The combined 5-year all-cause OS was 0.86 (95% CI, 0.84 to 0.88), and the combined 5-year disease-specific OS was 0.93 (95% CI, 0.91 to 0.94). The relationships between demographic and histopathologic factors and survival differed for all-cause and disease-specific survival outcomes, but no combined prognostic factor model was found to adequately classify patients at higher risk of recurrence or death as a result of colon cancer. Edrecolomab did not prolong survival. Consequently, this large study with a long duration of follow-up provided unique data concerning the natural history of resected stage II colon cancer. Prognostic factors identified in previous retrospective and pooled analyses were associated with survival outcomes in this stage II patient cohort. Results from ongoing molecular marker studies may enhance our ability to determine the risk profile of these patients.
Lee S. Schwartzberg - One of the best experts on this subject based on the ideXlab platform.
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adjuvant therapy with the monoclonal antibody Edrecolomab plus fluorouracil based therapy does not improve overall survival of patients with stage iii colon cancer
Journal of Clinical Oncology, 2009Co-Authors: Anthony L A Fields, Lee S. Schwartzberg, Alan M Keller, Stephen A Bernard, Carl Kardinal, Alan R Cohen, Joe Schulz, Peter D Eisenberg, John K Forster, Paul WisselAbstract:Purpose Edrecolomab (ED) is a murine monoclonal antibody targeting the EpCam antigen. This phase III randomized multicenter trial investigated the benefit of adding ED to fluorouracil (FU) based therapy in patients with stage III colorectal cancer. Patients and Methods Patients with stage III colon cancer were randomly assigned to one of two treatments after curative surgery. Patients in arm 1 received five infusions of ED together with FU-based chemotherapy; patients in arm 2 received FU-based chemotherapy alone. The primary end point was overall survival (OS). Results One thousand eight hundred thirty-nine patients were randomly assigned; results were analyzed on an intent-to-treat basis. Patient characteristics were well-balanced across treatment arms. Five-year follow-up has been completed. Patients randomly assigned to ED plus FU-based therapy showed a 5-year survival rate of 69.6% while for patients receiving FU-based therapy, the rate was 68.2%. The hazard ratio for death with ED plus FU-based ther...
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Adjuvant Therapy With the Monoclonal Antibody Edrecolomab Plus Fluorouracil-Based Therapy Does Not Improve Overall Survival of Patients With Stage III Colon Cancer
Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2009Co-Authors: Anthony L A Fields, Lee S. Schwartzberg, Alan M Keller, Stephen A Bernard, Carl Kardinal, Alan R Cohen, Joe Schulz, Peter D Eisenberg, John K Forster, Paul WisselAbstract:Edrecolomab (ED) is a murine monoclonal antibody targeting the EpCam antigen. This phase III randomized multicenter trial investigated the benefit of adding ED to fluorouracil (FU) based therapy in patients with stage III colorectal cancer. Patients with stage III colon cancer were randomly assigned to one of two treatments after curative surgery. Patients in arm 1 received five infusions of ED together with FU-based chemotherapy; patients in arm 2 received FU-based chemotherapy alone. The primary end point was overall survival (OS). One thousand eight hundred thirty-nine patients were randomly assigned; results were analyzed on an intent-to-treat basis. Patient characteristics were well-balanced across treatment arms. Five-year follow-up has been completed. Patients randomly assigned to ED plus FU-based therapy showed a 5-year survival rate of 69.6% while for patients receiving FU-based therapy, the rate was 68.2%. The hazard ratio for death with ED plus FU-based therapy compared to FU-based therapy was 0.896 (95% CI, 0.752 to 1.068), which was not statistically significant (P = .220). The adverse effect profiles of the two treatment arms were similar, with the main adverse effects being diarrhea, abdominal pain, and nausea. Anaphylaxis occurred in fewer than 1% of patients receiving ED. For patients with stage III colon cancer, the addition of ED to FU-based therapy had no statistically significant effect on OS.
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clinical experience with Edrecolomab a monoclonal antibody therapy for colorectal carcinoma
Critical Reviews in Oncology Hematology, 2001Co-Authors: Lee S. SchwartzbergAbstract:Edrecolomab (monoclonal antibody 17-1A) is a murine monoclonal antibody that recognizes the human tumor-associated antigen Ep-CAM (otherwise known as 17-1A). It is being developed for the adjuvant treatment of colorectal cancer. In a study of 189 patients with resected stage III colorectal cancer, treatment with Edrecolomab resulted in a 32% increase in overall survival compared with no treatment (P<0.01) and decreased the tumor recurrence rate by 23% (P<0.04). In terms of safety, Edrecolomab was well tolerated. Based on these study results, Edrecolomab is currently under investigation in large multicenter phase III studies both as monotherapy and in combination with 5-fluorouracil-based chemotherapy versus chemotherapy alone for the treatment of stage III colon cancer. Although these studies are still ongoing, an interim analysis of safety data indicated that the combination of Edrecolomab with chemotherapy is well tolerated. In addition, Edrecolomab monotherapy demonstrated a favorable safety profile compared with chemotherapy. Edrecolomab is also currently being tested in large multicenter adjuvant phase III studies in stage II/III rectal cancer and stage II colon cancer. Edrecolomab represents a novel therapeutic approach and has the potential to become a treatment of choice as monotherapy in stage II colon cancer and in combination with chemotherapy in stage II/III rectal and stage III colon cancer.
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Clinical experience with Edrecolomab: A monoclonal antibody therapy for colorectal carcinoma
Critical Reviews in Oncology Hematology, 2001Co-Authors: Lee S. SchwartzbergAbstract:Edrecolomab (monoclonal antibody 17-1A) is a murine monoclonal antibody that recognizes the human tumor-associated antigen Ep-CAM (otherwise known as 17-1A). It is being developed for the adjuvant treatment of colorectal cancer. In a study of 189 patients with resected stage III colorectal cancer, treatment with Edrecolomab resulted in a 32% increase in overall survival compared with no treatment (P
Rudolf Voigtmann - One of the best experts on this subject based on the ideXlab platform.
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sequential immunochemotherapy and Edrecolomab in the adjuvant therapy of breast cancer reduction of 17 1a positive disseminated tumour cells
Annals of Oncology, 2002Co-Authors: E. M. Kirchner, R. Gerhards, Rudolf VoigtmannAbstract:Abstract Background The aim of our study was to evaluate the efficacy of the monoclonal antibody Edrecolomab after chemo- and radiotherapy in the elimination of disseminated tumour cells in bone marrow in the adjuvant therapy of breast cancer. Patients and methods The bone marrow of 25 patients with breast cancer was tested for the presence of disseminated tumour cells using the pancytoceratine antibody and the alkaline phosphatase–anti-alkaline-phosphatase (APAAP) technique. To characterize tumour cells simultaneously, immunofluorescent double labelling of pancytoceratine and epithelial cell adhesion molecule (antibody 17-1A) was performed on tumour cells after magneto bead enrichment. Patients positive for the 17-1A antigen in bone marrow after chemotherapy were treated with Edrecolomab (500 mg Panorex® initially, then 100 mg/month over 4 months) and investigated for the presence of micrometastases 6 weeks after the last treatment. Results Of the 17 patients showing bone marrow micrometastases (BM-MM), 14 tested 17-1A positive before adjuvant chemotherapy. After chemotherapy, nine patients remained positive for the17-1A antigen and were treated with Edrecolomab. The final investigation after immunotherapy showed a complete elimination of the 17-1A-positive BM-MM in seven patients and a significant reduction of these cells in two patients. Conclusions Sequential treatment of breast cancer with Edrecolomab after adjuvant chemotherapy can reduce disseminated tumour cells in the bone marrow and eliminate 17-1A-positive micrometastases.
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Sequential immunochemotherapy and Edrecolomab in the adjuvant therapy of breast cancer: reduction of 17-1A-positive disseminated tumour cells
Annals of oncology : official journal of the European Society for Medical Oncology, 2002Co-Authors: E. M. Kirchner, R. Gerhards, Rudolf VoigtmannAbstract:The aim of our study was to evaluate the efficacy of the monoclonal antibody Edrecolomab after chemo- and radiotherapy in the elimination of disseminated tumour cells in bone marrow in the adjuvant therapy of breast cancer. The bone marrow of 25 patients with breast cancer was tested for the presence of disseminated tumour cells using the pancytoceratine antibody and the alkaline phosphatase-anti-alkaline-phosphatase (APAAP) technique. To characterize tumour cells simultaneously, immunofluorescent double labelling of pancytoceratine and epithelial cell adhesion molecule (antibody 17-1A) was performed on tumour cells after magneto bead enrichment. Patients positive for the 17-1A antigen in bone marrow after chemotherapy were treated with Edrecolomab (500 mg Panorex) initially, then 100 mg/month over 4 months) and investigated for the presence of micrometastases 6 weeks after the last treatment. Of the 17 patients showing bone marrow micrometastases (BM-MM), 14 tested 17-1A positive before adjuvant chemotherapy. After chemotherapy, nine patients remained positive for the 17-1A antigen and were treated with Edrecolomab. The final investigation after immunotherapy showed a complete elimination of the 17-1A-positive BM-MM in seven patients and a significant reduction of these cells in two patients. Sequential treatment of breast cancer with Edrecolomab after adjuvant chemotherapy can reduce disseminated tumour cells in the bone marrow and eliminate 17-1A-positive micrometastases.
D J Kerr - One of the best experts on this subject based on the ideXlab platform.
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documenting the natural history of patients with resected stage ii adenocarcinoma of the colon after random assignment to adjuvant treatment with Edrecolomab or observation results from calgb 9581
Journal of Clinical Oncology, 2011Co-Authors: Donna Niedzwiecki, Monica M Bertagnolli, Robert S Warren, Carolyn C Compton, Nancy E Kemeny, Al B Benson, Gail S Eckhardt, Steven R Alberts, Gity N Porjosh, D J KerrAbstract:Purpose We conducted a randomized trial comparing adjuvant treatment with Edrecolomab versus observation in patients with resected, low-risk, stage II colon cancer. This study also prospectively studied patient- and tumor-specific markers of treatment outcome. Patients and Methods After surgical resection, patients with stage II colon cancer were randomly assigned to either five infusions of Edrecolomab at 28-day intervals or observation without adjuvant therapy. Results Final accrual included 1,738 patients; 865 patients received Edrecolomab, and 873 patients were observed without adjuvant treatment. Median follow-up time was 7.9 years. There were no significant outcome differences between study arms (overall survival [OS], P = .71; disease-free survival, P = .64). The combined 5-year all-cause OS was 0.86 (95% CI, 0.84 to 0.88), and the combined 5-year disease-specific OS was 0.93 (95% CI, 0.91 to 0.94). The relationships between demographic and histopathologic factors and survival differed for all-caus...
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Documenting the Natural History of Patients With Resected Stage II Adenocarcinoma of the Colon After Random Assignment to Adjuvant Treatment With Edrecolomab or Observation: Results From CALGB 9581
Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2011Co-Authors: Donna Niedzwiecki, Monica M Bertagnolli, Robert S Warren, Carolyn C Compton, Nancy E Kemeny, Al B Benson, Steven R Alberts, Gity N Porjosh, S. Gail Eckhardt, D J KerrAbstract:We conducted a randomized trial comparing adjuvant treatment with Edrecolomab versus observation in patients with resected, low-risk, stage II colon cancer. This study also prospectively studied patient- and tumor-specific markers of treatment outcome. After surgical resection, patients with stage II colon cancer were randomly assigned to either five infusions of Edrecolomab at 28-day intervals or observation without adjuvant therapy. Final accrual included 1,738 patients; 865 patients received Edrecolomab, and 873 patients were observed without adjuvant treatment. Median follow-up time was 7.9 years. There were no significant outcome differences between study arms (overall survival [OS], P = .71; disease-free survival, P = .64). The combined 5-year all-cause OS was 0.86 (95% CI, 0.84 to 0.88), and the combined 5-year disease-specific OS was 0.93 (95% CI, 0.91 to 0.94). The relationships between demographic and histopathologic factors and survival differed for all-cause and disease-specific survival outcomes, but no combined prognostic factor model was found to adequately classify patients at higher risk of recurrence or death as a result of colon cancer. Edrecolomab did not prolong survival. Consequently, this large study with a long duration of follow-up provided unique data concerning the natural history of resected stage II colon cancer. Prognostic factors identified in previous retrospective and pooled analyses were associated with survival outcomes in this stage II patient cohort. Results from ongoing molecular marker studies may enhance our ability to determine the risk profile of these patients.
Daniel G. Haller - One of the best experts on this subject based on the ideXlab platform.
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Update of clinical trials with Edrecolomab: A monoclonal antibody therapy for colorectal cancer
Seminars in Oncology, 2001Co-Authors: Daniel G. HallerAbstract:Edrecolomab is a murine IgG2a monoclonal antibody that recognizes the tumor-associated antigen Ep-CAM. Its antitumor effects are mediated through antibody-dependent cellular cytotoxicity, complement-mediated cytolysis, and the induction of an anti-idiotypic network. An initial study of 189 patients with resected stage III colorectal cancer showed that Edrecolomab reduced the relative risk of mortality by 32% compared with observation alone (P < .01). Edrecolomab has now been investigated in two large phase III studies of patients with stage III colon cancer, either as a single agent or in combination with 5-FU-based chemotherapy. Preliminary safety data have shown that Edrecolomab is well tolerated when used as monotherapy and adds little to chemotherapy-related side effects when used in combination. Edrecolomab is also being studied as monotherapy following resection of stage II colon cancer, and in combination with chemotherapy in patients with resected stage II or III rectal cancer. In conclusion, Edrecolomab is a novel biological therapy for the adjuvant treatment of colorectal cancer. Completed and ongoing trials may support its use as monotherapy in stage II colon cancer or in combination with chemotherapy in stage III colon cancer and stage II/III rectal cancer.
