HER2 Support Group Forums - View Single Post - preclinical: metronomic chemotherapy (oral) produced remarkable prolongn of survival

Rich66 · 11-18-2009, 11:39 AM

Maybe "mabs" and metronomics are compatible:

YM BIOSCIENCES ANNOUNCES NIMOTUZUMAB RESULTS IN ADVANCED TRIPLE-NEGATIVE BREAST CANCER MODEL PRESENTED AT AACR-NCI-EORTC MEETING
MISSISSAUGA, ON, Nov. 18 /PRNewswire-FirstCall/ - YM BioSciences Inc. (NYSE Amex: YMI; TSX: YM), a life sciences product development company that identifies and advances a diverse portfolio of promising cancer-related products at various stages of development, announced that results from a study evaluating nimotuzumab were presented today in a poster at the 2009 AACR-NCI-EORTC Molecular Targets and Cancer Therapeutics conference in Boston, Massachusetts. The reported results demonstrate that nimotuzumab in combination with metronomic chemotherapy in an advanced triple-negative breast cancer preclinical model is safe and effective.
In this study nimotuzumab, an epidermal growth factor receptor (EGFR) targeting antibody, was administered twice weekly in combination with metronomic (continuous low-dose) cyclophosphamide. This regimen resulted in significant primary tumor growth delay in an aggressive, metastatic, higher EGFR-expressing variant of the MDA-MB-231 human breast cancer breast model, which over-expresses EGFR. In addition, the combination resulted in a significant survival advantage over cyclophosphamide alone.

"The data demonstrate that nimotuzumab in combination with metronomic cyclophosphamide is safe and effective in this aggressive tumor type which has limited therapeutic options. Furthermore, the addition of nimotuzumab would be expected to be minimally toxic to patients and as such, this combination should be considered for this patient population in future clinical trials," said lead author Dr.
Anthony J. Mutsaers of the Division of Molecular and Cellular Biology Research, Sunnybrook Health Sciences Centre and Department of Medical Biophysics, University of Toronto.
The research poster is entitled "Combination treatment with metronomic cyclophosphamide and the EGFR monoclonal antibody nimotuzumab is efficacious and non-toxic in a preclinical model of advanced triple negative breast cancer". It is being presented today (Poster Session C, Abstract C49) by the author.

YM BioSciences Reports CYT997 Oral Vascular Disrupting Agent Results Presented at AACR-NCI-EORTC Meeting
MISSISSAUGA, Canada – November 16, 2009 – YM BioSciences Inc. (NYSE Amex: YMI; TSX: YM),a life sciences product development company that identifies and advances a diverse portfolio of promising cancer-related products at various stages of development, announced that preclinical results for CYT997 were presented today in a poster by Cytopia Limited (ASX:CYT) at the 2009 AACR-NCI-EORTC Molecular Targets and Cancer Therapeutics conference in Boston, Massachusetts. CYT997 is an orally available, small molecule vascular disrupting agent (VDA) currently in Phase II clinical studies. A proposal to merge Cytopia into YM has been previously announced and is pending approval by Cytopia shareholders, Australian court and other regulatory approvals.

The results reportedly demonstrate that when administered metronomically (in frequent, low doses), CYT997 is able to produce potent vascular disrupting effects in tumors (colon adenocarcinoma xenograft model), and in combination with cisplatin dosed weekly leads to enhanced antitumor effects compared to cisplatin alone. Administration of CYT997 reportedly resulted in a time and concentration-dependent shutdown of tumor vasculature. Daily administration of CYT997 reportedly resulted in a sustained shutdown of tumour vasculature, increased necrosis and increased survival.
“The results of this study appear to demonstrate the broad potential utility of CYT997 as an anticancer agent. The ability to administer CYT997 orally differentiates it from most other VDAs in development and allows more flexible dosing regimes than would be possible for agents that can only be administered intravenously,” said Chris Burns, Director of Research of Cytopia.
“Metronomic administration of a VDA may likely result in more consistent and prolonged collapse of tumor vasculature and an orally administered VDA would be ideal for this type of administration,” noted Dr. Robert Kerbel, Professor (adjunct), Cancer Biology, Medicine, MD Anderson Cancer Center, University of Texas and Professor, Medical Biophysics, University of Toronto.
Dr. Chris Burns presented the poster entitled, “Antitumour activity of CYT997: A Phase II vascular disrupting agent administered orally in combination with cisplatin in a colon adenocarcinoma xenograft mode” at the Angiogenesis and Antiangiogenesis Agents poster session on Monday, 16 November 2009.
“CYT997 is substantially distinct from the other VDAs in that it can be delivered orally, as well as intravenously, facilitating more frequent administration at lower doses, a regimen likely to enhance both its safety and efficacy. We believe this unique aspect of CYT997 could significantly expand its utility and that its development could add to existing treatment protocols and lead to new and important regimens for a wide range of tumour types,” said David Allan, Chairman and CEO of YM BioSciences.

Continuous low-dose therapy with vinblastine and VEGF receptor-2 antibody induces sustained tumor regression without overt toxicity

FULL TEXT LINK

Giannoula Klement¹, Sylvain Baruchel², Janusz Rak¹, Shan Man¹, Katherine Clark¹, Daniel J. Hicklin³, Peter Bohlen³ and Robert S. Kerbel¹
¹Sunnybrook and Women's College Health Sciences Centre, Biological Sciences Program, Division of Cancer Biology Research, and Toronto-Sunnybrook Regional Cancer Centre, Toronto, Ontario M4N 3M5, Canada; Department of Medical Biophysics, University of Toronto, Ontario, Canada
²Hospital for Sick Children, Department of Pediatrics, Division of Hematology/Oncology, New Agent and Innovative Therapy Program, Toronto, Ontario M5G 1X8, Canada
³ImClone Systems Inc., New York, New York 10014, USA
Address correspondence to: Robert S. Kerbel, Sunnybrook and Women’s College Health Sciences Centre, Biological Sciences, Division of Cancer Biology Research, Room S-218, 2075 Bayview Avenue, Toronto, Ontario M4N 3M5, Canada. Phone: (416) 480-5711; Fax: (416) 480-5703; E-mail: kerbel@srcl.sunnybrook.utoronto.ca.
Published April 15, 2000
Received for publication November 2, 1999, and accepted in revised form February 25, 2000.

Various conventional chemotherapeutic drugs can block angiogenesis or even kill activated, dividing endothelial cells. Such effects may contribute to the antitumor efficacy of chemotherapy in vivo and may delay or prevent the acquisition of drug-resistance by cancer cells. We have implemented a treatment regimen that augments the potential antivascular effects of chemotherapy, that is devoid of obvious toxic side effects, and that obstructs the development of drug resistance by tumor cells. Xenografts of 2 independent neuroblastoma cell lines were subjected to either continuous treatment with low doses of vinblastine, a monoclonal neutralizing antibody (DC101) targeting the flk-1/KDR (type 2) receptor for VEGF, or both agents together. The rationale for this combination was that any antivascular effects of the low-dose chemotherapy would be selectively enhanced in cells of newly formed vessels when survival signals mediated by VEGF are blocked. Both DC101 and low-dose vinblastine treatment individually resulted in significant but transient xenograft regression, diminished tumor vascularity, and direct inhibition of angiogenesis. Remarkably, the combination therapy resulted in full and sustained regressions of large established tumors, without an ensuing increase in host toxicity or any signs of acquired drug resistance during the course of treatment, which lasted for >6 months.
This article may have been published online in advance of the print edition. The date of publication is available
from the JCI website, http://www.jci.org. J. Clin. Invest.105:R15–R24 (2000).

11-18-2009, 11:39 AM	#15
Rich66 Senior Member Join Date: Feb 2008 Location: South East Wisconsin Posts: 3,431	Re: preclinical: metronomic chemotherapy (oral) produced remarkable prolongn of survi Maybe "mabs" and metronomics are compatible: YM BIOSCIENCES ANNOUNCES NIMOTUZUMAB RESULTS IN ADVANCED TRIPLE-NEGATIVE BREAST CANCER MODEL PRESENTED AT AACR-NCI-EORTC MEETING MISSISSAUGA, ON, Nov. 18 /PRNewswire-FirstCall/ - YM BioSciences Inc. (NYSE Amex: YMI; TSX: YM), a life sciences product development company that identifies and advances a diverse portfolio of promising cancer-related products at various stages of development, announced that results from a study evaluating nimotuzumab were presented today in a poster at the 2009 AACR-NCI-EORTC Molecular Targets and Cancer Therapeutics conference in Boston, Massachusetts. The reported results demonstrate that nimotuzumab in combination with metronomic chemotherapy in an advanced triple-negative breast cancer preclinical model is safe and effective. In this study nimotuzumab, an epidermal growth factor receptor (EGFR) targeting antibody, was administered twice weekly in combination with metronomic (continuous low-dose) cyclophosphamide. This regimen resulted in significant primary tumor growth delay in an aggressive, metastatic, higher EGFR-expressing variant of the MDA-MB-231 human breast cancer breast model, which over-expresses EGFR. In addition, the combination resulted in a significant survival advantage over cyclophosphamide alone. "The data demonstrate that nimotuzumab in combination with metronomic cyclophosphamide is safe and effective in this aggressive tumor type which has limited therapeutic options. Furthermore, the addition of nimotuzumab would be expected to be minimally toxic to patients and as such, this combination should be considered for this patient population in future clinical trials," said lead author Dr. Anthony J. Mutsaers of the Division of Molecular and Cellular Biology Research, Sunnybrook Health Sciences Centre and Department of Medical Biophysics, University of Toronto. The research poster is entitled "Combination treatment with metronomic cyclophosphamide and the EGFR monoclonal antibody nimotuzumab is efficacious and non-toxic in a preclinical model of advanced triple negative breast cancer". It is being presented today (Poster Session C, Abstract C49) by the author. YM BioSciences Reports CYT997 Oral Vascular Disrupting Agent Results Presented at AACR-NCI-EORTC Meeting MISSISSAUGA, Canada – November 16, 2009 – YM BioSciences Inc. (NYSE Amex: YMI; TSX: YM),a life sciences product development company that identifies and advances a diverse portfolio of promising cancer-related products at various stages of development, announced that preclinical results for CYT997 were presented today in a poster by Cytopia Limited (ASX:CYT) at the 2009 AACR-NCI-EORTC Molecular Targets and Cancer Therapeutics conference in Boston, Massachusetts. CYT997 is an orally available, small molecule vascular disrupting agent (VDA) currently in Phase II clinical studies. A proposal to merge Cytopia into YM has been previously announced and is pending approval by Cytopia shareholders, Australian court and other regulatory approvals. The results reportedly demonstrate that when administered metronomically (in frequent, low doses), CYT997 is able to produce potent vascular disrupting effects in tumors (colon adenocarcinoma xenograft model), and in combination with cisplatin dosed weekly leads to enhanced antitumor effects compared to cisplatin alone. Administration of CYT997 reportedly resulted in a time and concentration-dependent shutdown of tumor vasculature. Daily administration of CYT997 reportedly resulted in a sustained shutdown of tumour vasculature, increased necrosis and increased survival. “The results of this study appear to demonstrate the broad potential utility of CYT997 as an anticancer agent. The ability to administer CYT997 orally differentiates it from most other VDAs in development and allows more flexible dosing regimes than would be possible for agents that can only be administered intravenously,” said Chris Burns, Director of Research of Cytopia. “Metronomic administration of a VDA may likely result in more consistent and prolonged collapse of tumor vasculature and an orally administered VDA would be ideal for this type of administration,” noted Dr. Robert Kerbel, Professor (adjunct), Cancer Biology, Medicine, MD Anderson Cancer Center, University of Texas and Professor, Medical Biophysics, University of Toronto. Dr. Chris Burns presented the poster entitled, “*Antitumour activity of CYT997: A Phase II vascular disrupting agent administered orally in combination with cisplatin in a colon adenocarcinoma xenograft mode” at the Angiogenesis and Antiangiogenesis Agents poster session on Monday, 16 November 2009. “CYT997 is substantially distinct from the other VDAs in that it can be delivered orally, as well as intravenously, facilitating more frequent administration at lower doses, a regimen likely to enhance both its safety and efficacy. We believe this unique aspect of CYT997 could significantly expand its utility and that its development could add to existing treatment protocols and lead to new and important regimens for a wide range of tumour types,” said David Allan, Chairman and CEO of YM BioSciences. Continuous low-dose therapy with vinblastine and VEGF receptor-2 antibody induces sustained tumor regression without overt toxicity* FULL TEXT LINK Giannoula Klement¹, Sylvain Baruchel², Janusz Rak¹, Shan Man¹, Katherine Clark¹, Daniel J. Hicklin³, Peter Bohlen³ and Robert S. Kerbel¹ ¹Sunnybrook and Women's College Health Sciences Centre, Biological Sciences Program, Division of Cancer Biology Research, and Toronto-Sunnybrook Regional Cancer Centre, Toronto, Ontario M4N 3M5, Canada; Department of Medical Biophysics, University of Toronto, Ontario, Canada ²Hospital for Sick Children, Department of Pediatrics, Division of Hematology/Oncology, New Agent and Innovative Therapy Program, Toronto, Ontario M5G 1X8, Canada ³ImClone Systems Inc., New York, New York 10014, USA Address correspondence to: Robert S. Kerbel, Sunnybrook and Women’s College Health Sciences Centre, Biological Sciences, Division of Cancer Biology Research, Room S-218, 2075 Bayview Avenue, Toronto, Ontario M4N 3M5, Canada. Phone: (416) 480-5711; Fax: (416) 480-5703; E-mail: kerbel@srcl.sunnybrook.utoronto.ca. Published April 15, 2000 Received for publication November 2, 1999, and accepted in revised form February 25, 2000. Various conventional chemotherapeutic drugs can block angiogenesis or even kill activated, dividing endothelial cells. Such effects may contribute to the antitumor efficacy of chemotherapy in vivo and may delay or prevent the acquisition of drug-resistance by cancer cells. We have implemented a treatment regimen that augments the potential antivascular effects of chemotherapy, that is devoid of obvious toxic side effects, and that obstructs the development of drug resistance by tumor cells. Xenografts of 2 independent neuroblastoma cell lines were subjected to either continuous treatment with low doses of vinblastine, a monoclonal neutralizing antibody (DC101) targeting the flk-1/KDR (type 2) receptor for VEGF, or both agents together. The rationale for this combination was that any antivascular effects of the low-dose chemotherapy would be selectively enhanced in cells of newly formed vessels when survival signals mediated by VEGF are blocked. Both DC101 and low-dose vinblastine treatment individually resulted in significant but transient xenograft regression, diminished tumor vascularity, and direct inhibition of angiogenesis. Remarkably, the combination therapy resulted in full and sustained regressions of large established tumors, without an ensuing increase in host toxicity or any signs of acquired drug resistance during the course of treatment, which lasted for >6 months. This article may have been published online in advance of the print edition. The date of publication is available from the JCI website, http://www.jci.org. J. Clin. Invest.105:R15–R24 (2000). __________________ Mom's treatment history (link)