HER2 Support Group Forums - View Single Post - Anybody with experience of Quadramet and/or Sorafenib?

pattyz · 07-22-2007, 05:46 AM

Ragini!
It is good to see your name, tho' not so with your continuing progression.

I am pasting info here on a promising 'new' drug that is available 'out there', not in the US yet, but maybe to you.

I am also putting info on the Sorafenib here. One, a post from Emmay, the other general information. I so hope it will be of some small help to you. Hugs with more hope to you,
pattyz xoxo

Date: Tue Jul 10 2007 - 14:47:23 EDT

About Rexin-G™

Scientists at Epeius Biotechnologies have developed the technologies that can deliver a new class of powerful biological therapy directly to tumors that have spread throughout the body (metastatic cancer). The lead product, Rexin-G™ , is a gene delivery vehicle, a tumor-targeted nanoparticle that is designed to deliver a tumor-killing designer gene precisely where it is needed. Rexin-G™ has been shown clinically to be highly active against a broad spectrum of chemo-resistant tumor types, causing tumor shrinkage in patients suffering from metastatic cancer, without eliciting harmful systemic side effects.
Milestones
Rexin-G™ received orphan drug designation by the U.S. Food and Drug Administration
Rexin-G™ received accelerated approval in the Philippines for use in all solid tumors
Rexin-G™ is currently in clinical trials internationally, including the U.S., for advanced pancreatic and other metastatic cancer
How Rexin-G™ Works
Each nanoparticle of Rexin-G™ is only 100 nanometers wide; yet despite its small size, it is a highly complex structure. Each component—the envelope, matrix, capsid, enzymes, and genetic material has its purpose, and in concert they enable each nanoparticle to deliver a lethal payload. The payload is a tumor-killing designer gene, which selectively kills cancer cells and their associated blood supply, while sparing normal cells and healthy tissues.
The delivery of the lethal payload by the nanoparticles is "pathotropic," meaning it is specifically targeted to diseased tissues. Rather than targeting the cancer cells themselves, Rexin-G™ efficiently targets a common histopathological property of all invasive tumors. Pathotropic targeting allows Rexin-G™ to seek out and destroy tumors regardless of their location in the body, thereby reducing tumor burden, prolonging survival, and enhancing the patient’s quality-of-life.
Highlights
The only targeted cancer gene delivery system that can be effectively administered intravenously
Designed to seek out and destroy both primary and metastatic tumors
Highly active as a single agent in a broad spectrum of chemo-resistant cancers
About Metastatic Cancer
Cancer is a progressive illness, originating from primary tumors located in specific tissues or organs. Tumor cells detach from the primary tumor and are carried to other sites in the body through the bloodstream to neighboring tissues, creating a secondary or metastatic tumor. Metastatic tumors often present in essential organs, making treatment difficult. Common treatment options for metastatic tumors include chemotherapy, radiation therapy, surgery or combinations of these treatment options, which often have limited success while causing severe side effects that significantly diminish the quality of life for the patient.
Clinical Experience with Rexin-G™

Early clinical and preclinical data suggest that Rexin-G™ is safe and effective when used as a single agent therapeutic for the treatment of chemo-resistant tumors.
United States
Rexin-G™ is currently in Phase I trials at the Mayo Clinic in Rochester, Minnesota for locally advanced and metastatic pancreatic cancer that is refractory to traditional chemotherapy.
A single-use clinical trial evaluating Rexin-G™ for the treatment of metastatic cancer that is refractory to standard chemotherapy has been initiated at the University of Texas M.D. Anderson Cancer Center, Houston, Texas, Pittsburgh Hillman Cancer Center, Pittsburgh, PA., The Sarcoma Oncology Clinic, Santa Monica, CA. and the Epeius Clinical Research Unit, San Marino, CA.
Philippines
Rexin-G™ has been granted accelerated approval for the treatment of all solid tumors. Rexin-G™ has also been approved for the Expanded Access Program by the Bureau of Food and Drugs in the Philippines. Under these programs in the Philippines, Rexin-G™ is approved for use as a first-line and adjuvant therapy for pancreatic and breast cancer and a second-line therapy for all other solid tumors that are refractory to standard chemotherapy.
Japan
Dr. Takaki Imamura has initiated an independent study of Rexin-G™ in a variety of metastatic cancers. He completed his first round of trials in December 2006. www.epieusbiotech.com

Patty,
We met with my sister's neuro-oncologist, who suggested a combination of Temodar/Sorafenib. The Sorafenib (also known as Nexavar, and "a sister compound" of Sutent) is an antiangiogenesis drug. I asked about the combo of Temodar/Xeloda, and she said that might be another option, but the neuro-oncologist is seeing some very early encouraging results with Sorafenib/Temodar combo. She said they are "radiation sensitizers", so she would like my sister to start the protocol(if she choses it) before her next CyberKnife treatment.

The most common side-efffect of Sorafenib seems to be a rash on the hands and/or feet, which subsides when treatment is interrupted, and sometimes doesn't return when treatment is started up again. Emmay

Angiogenesis Inhibitors in Lung Cancer
Phase II results of three anti-angiogenesis drugs were presented: 1) ZD6474 (Zactima) 2) Sunitinib (Sutent) 3) Sorafenib (Nexavar) – these three drugs are all generally anti-angiogenesis inhibitors like bevacizumab (Avastin), but Avastin is given intravenously and these are oral drugs, which may have a benefit in terms of side effects. Also, these drugs each inhibit more multiple receptors than does Avastin.
2) Sutent inhibits a number of different receptors re: angiogenesis. Study’s main outcome was Objective Response, i.e. tumor shrinkage. Study done with people with previously treated advanced lung cancer. Adverse events were evident, 38% of participants discontinued on the drug. There were 3 deaths, although probably only 1 was truly study related. A majority of participants had tumor shrinkage. Progression free survival (PFS) was 11.3 weeks, overall survival was 23.9 weeks. The response rates were comparable to previously approved agents, according to Dr. Socinski, who presented these data. In this Phase II study, Sutent wasn’t compared to another treatment. That will likely be done in a Phase III study. (Socinski-Abstract 7001)
3) Sorafenib was tested as a single agent in advanced non-small-cell lung cancer. Sorafenib inhibits many different receptors. The primary endpoint was Response, as in the Sutent trial. Sorafenib wasn’t compared to another drug in this Phase II study. People with brain metastases and squamous cell carcinoma participated in this study. This is notable because in the Avastin trial, researchers had to exclude people with these because of risks of bleeding and other side effects. Outcome was Progression Free Survival (PFS) of 2.7 months (about 10.8 weeks). Median overall survival 6.7 months (about 26.8 weeks), which is similar to Iressa and Tarceva. 59% of patients had clinical benefit. Were no serious side effects, 8% did have bleeding. A Phase III is currently recruiting patients. (Gatzmeier-Abstract 7002)
Summary – all these trials showed these drugs worked alone, that is, not in combination with chemotherapy. But, it is most likely that they will be used in combination with chemotherapy and/or biologics, if approved. All three drugs are hitting multiple targets, which makes things complicated. Dr. Roy Herbst compared the outcomes of these trials to Phase I/II data of Tarceva plus Avastin, which had higher PFS (6.2 months-Herbst RS et al. JCO April 10, 2005). The drugs reported on at ASCO 2006 may not provide a large advantage in survival, but would likely have many fewer side effects than chemotherapy (Abstracts 7000-7002).

07-22-2007, 05:46 AM	#3
pattyz Senior Member Join Date: Mar 2006 Posts: 306	Ragini! It is good to see your name, tho' not so with your continuing progression. I am pasting info here on a promising 'new' drug that is available 'out there', not in the US yet, but maybe to you. I am also putting info on the Sorafenib here. One, a post from Emmay, the other general information. I so hope it will be of some small help to you. Hugs with more hope to you, pattyz xoxo Date: Tue Jul 10 2007 - 14:47:23 EDT About Rexin-G™ Scientists at Epeius Biotechnologies have developed the technologies that can deliver a new class of powerful biological therapy directly to tumors that have spread throughout the body (metastatic cancer). The lead product, Rexin-G™ , is a gene delivery vehicle, a tumor-targeted nanoparticle that is designed to deliver a tumor-killing designer gene precisely where it is needed. Rexin-G™ has been shown clinically to be highly active against a broad spectrum of chemo-resistant tumor types, causing tumor shrinkage in patients suffering from metastatic cancer, without eliciting harmful systemic side effects. Milestones Rexin-G™ received orphan drug designation by the U.S. Food and Drug Administration Rexin-G™ received accelerated approval in the Philippines for use in all solid tumors Rexin-G™ is currently in clinical trials internationally, including the U.S., for advanced pancreatic and other metastatic cancer How Rexin-G™ Works Each nanoparticle of Rexin-G™ is only 100 nanometers wide; yet despite its small size, it is a highly complex structure. Each component—the envelope, matrix, capsid, enzymes, and genetic material has its purpose, and in concert they enable each nanoparticle to deliver a lethal payload. The payload is a tumor-killing designer gene, which selectively kills cancer cells and their associated blood supply, while sparing normal cells and healthy tissues. The delivery of the lethal payload by the nanoparticles is "pathotropic," meaning it is specifically targeted to diseased tissues. Rather than targeting the cancer cells themselves, Rexin-G™ efficiently targets a common histopathological property of all invasive tumors. Pathotropic targeting allows Rexin-G™ to seek out and destroy tumors regardless of their location in the body, thereby reducing tumor burden, prolonging survival, and enhancing the patient’s quality-of-life. Highlights The only targeted cancer gene delivery system that can be effectively administered intravenously Designed to seek out and destroy both primary and metastatic tumors Highly active as a single agent in a broad spectrum of chemo-resistant cancers About Metastatic Cancer Cancer is a progressive illness, originating from primary tumors located in specific tissues or organs. Tumor cells detach from the primary tumor and are carried to other sites in the body through the bloodstream to neighboring tissues, creating a secondary or metastatic tumor. Metastatic tumors often present in essential organs, making treatment difficult. Common treatment options for metastatic tumors include chemotherapy, radiation therapy, surgery or combinations of these treatment options, which often have limited success while causing severe side effects that significantly diminish the quality of life for the patient. Clinical Experience with Rexin-G™ Early clinical and preclinical data suggest that Rexin-G™ is safe and effective when used as a single agent therapeutic for the treatment of chemo-resistant tumors. United States Rexin-G™ is currently in Phase I trials at the Mayo Clinic in Rochester, Minnesota for locally advanced and metastatic pancreatic cancer that is refractory to traditional chemotherapy. A single-use clinical trial evaluating Rexin-G™ for the treatment of metastatic cancer that is refractory to standard chemotherapy has been initiated at the University of Texas M.D. Anderson Cancer Center, Houston, Texas, Pittsburgh Hillman Cancer Center, Pittsburgh, PA., The Sarcoma Oncology Clinic, Santa Monica, CA. and the Epeius Clinical Research Unit, San Marino, CA. Philippines Rexin-G™ has been granted accelerated approval for the treatment of all solid tumors. Rexin-G™ has also been approved for the Expanded Access Program by the Bureau of Food and Drugs in the Philippines. Under these programs in the Philippines, Rexin-G™ is approved for use as a first-line and adjuvant therapy for pancreatic and breast cancer and a second-line therapy for all other solid tumors that are refractory to standard chemotherapy. Japan Dr. Takaki Imamura has initiated an independent study of Rexin-G™ in a variety of metastatic cancers. He completed his first round of trials in December 2006. www.epieusbiotech.com Patty, We met with my sister's neuro-oncologist, who suggested a combination of Temodar/Sorafenib. The Sorafenib (also known as Nexavar, and "a sister compound" of Sutent) is an antiangiogenesis drug. I asked about the combo of Temodar/Xeloda, and she said that might be another option, but the neuro-oncologist is seeing some very early encouraging results with Sorafenib/Temodar combo. She said they are "radiation sensitizers", so she would like my sister to start the protocol(if she choses it) before her next CyberKnife treatment. The most common side-efffect of Sorafenib seems to be a rash on the hands and/or feet, which subsides when treatment is interrupted, and sometimes doesn't return when treatment is started up again. Emmay Angiogenesis Inhibitors in Lung Cancer Phase II results of three anti-angiogenesis drugs were presented: 1) ZD6474 (Zactima) 2) Sunitinib (Sutent) 3) Sorafenib (Nexavar) – these three drugs are all generally anti-angiogenesis inhibitors like bevacizumab (Avastin), but Avastin is given intravenously and these are oral drugs, which may have a benefit in terms of side effects. Also, these drugs each inhibit more multiple receptors than does Avastin. 2) Sutent inhibits a number of different receptors re: angiogenesis. Study’s main outcome was Objective Response, i.e. tumor shrinkage. Study done with people with previously treated advanced lung cancer. Adverse events were evident, 38% of participants discontinued on the drug. There were 3 deaths, although probably only 1 was truly study related. A majority of participants had tumor shrinkage. Progression free survival (PFS) was 11.3 weeks, overall survival was 23.9 weeks. The response rates were comparable to previously approved agents, according to Dr. Socinski, who presented these data. In this Phase II study, Sutent wasn’t compared to another treatment. That will likely be done in a Phase III study. (Socinski-Abstract 7001) 3) Sorafenib was tested as a single agent in advanced non-small-cell lung cancer. Sorafenib inhibits many different receptors. The primary endpoint was Response, as in the Sutent trial. Sorafenib wasn’t compared to another drug in this Phase II study. People with brain metastases and squamous cell carcinoma participated in this study. This is notable because in the Avastin trial, researchers had to exclude people with these because of risks of bleeding and other side effects. Outcome was Progression Free Survival (PFS) of 2.7 months (about 10.8 weeks). Median overall survival 6.7 months (about 26.8 weeks), which is similar to Iressa and Tarceva. 59% of patients had clinical benefit. Were no serious side effects, 8% did have bleeding. A Phase III is currently recruiting patients. (Gatzmeier-Abstract 7002) Summary – all these trials showed these drugs worked alone, that is, not in combination with chemotherapy. But, it is most likely that they will be used in combination with chemotherapy and/or biologics, if approved. All three drugs are hitting multiple targets, which makes things complicated. Dr. Roy Herbst compared the outcomes of these trials to Phase I/II data of Tarceva plus Avastin, which had higher PFS (6.2 months-Herbst RS et al. JCO April 10, 2005). The drugs reported on at ASCO 2006 may not provide a large advantage in survival, but would likely have many fewer side effects than chemotherapy (Abstracts 7000-7002).