Anybody with experience of Quadramet and/or Sorafenib?

[Ragini]

After having virtually exhausted the entire arsenal of available drugs for breast cancer, and still showing signs of disease progression, I am now wondering what other options I have.
My onc wants to go back to anthracyclines (Doxil) which I had when I was first diagnosed with metastatic disease. I decided to get a second opinion and talked to an American oncologist who recently moved here to Singapore.
Since I am suffering from significant pain from my bone mets, he suggested using Quadramet to first address that, and then going on to Sorafenib + Gemzar as the next line of treatment for the cancer.

I read up about Quadramet, but it seems to whack the bone marrow quite hard and I'm not sure how much relief it will give. After all the treatment lines I've been through, I reckon I don't have much marrow left.
Is there anybody out there who has been on Quadramet after having had long-term treatment for metastatic disease? If so, what was your experience.

Sorafenib worries me a bit since these kind of drugs which inhibit the formation of blood vessels for the tumours could apparently cause bleeding elsewhere. Since I've also had a craniotomy in the past for a brain met, I'm worried about the risk of brain hemmorhages if I take on this drug.
Is there anybody out there who's been on Sorafenib for breast cancer and who can give me some feedback on their experience.

My prayers & hugs to all of you
Ragini

[jones7676]

I don't have any experience with either of those drugs, but I have seen studies posted on this board that indicate that the anthracyclines can/do work even when used mulitple times. Whatever you decide I hope that the combo you pick works. Please keep us posted on your progress. We will be all be rallying for you. Barb

[pattyz]

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).

[Carolyns]

Ragani,

I do not have any words of wisdom for you. I just wanted to send you my well wishes and tell you that you are in my prayers.

PattyZ - thank you for your contributions to the board and for sharing your wisdom and knowledge.

Love, Hope, Peace,

Carolyn

[Emmay]

Hi Ragini,

My sister has had two craniotomies, WBR (Whole Brain Radiation), and multiple CyberKnife and stereotactic radiation treatments for brain mets (Herceptin seems to be working well for her in the rest of her body, but doesn't cross the blood-brain barrier). She was first diagnosed stage 2A in 6/03).

She has been taking Temodar and Sorafenib since Feb. 07, and brain mets have stopped appearing since (before that, she'd tried an early Lapatinib (Tykerb) trial, which didn't work for her, and a new 2-3 mets were appearing consistently, 2 months after each Cyberknife treatment, for a year(though the treated mets were arrested).

Both Sorafenib and Temodar are taken in pill form. The only major side effect she's experienced with Sorafenib is a loss of appetite. Her Temodar side effects are mainly mild fatigue and diahhrea - the loss of appetite combined with diahhrea whenever she did eat, caused her to lose weight fairly quickly. Her neuro-oncologist has adjusted her dosing a couple of times: she alternates weeks being on and off Temodar, and her Sorafenib dose was decreased somewhat. She is not on a clinical trial, but her neuro-oncologist said she has been starting to see encouraging results from the use of this combo in people with brain mets from renal cancer, melanoma, and breast cancer.

My sister is 5'4", 50 yrs old, and weighs 103 lbs. She says she feels quite good, and after the weight gain that accompanied the Decadron she took during previous brain treatments, she's enjoying being as slim as she was in high school. Also, she has settled on a way to control the diahhrea: she now takes 2 Immodium tabs/day, 1 in a.m., 1 at p.m, and her weight seems to have stabilized.

Her memory is still remarkably good - only her short-term memory is impaired very slightly. She is being treated in Boston.

Hearing and reading the potential side effects from any of the treatments can cause great apprehension - but it's important to keep in mind that the percentage of people who experience the worst of the side effects is usually quite low. I wish you every success and blessing with whatever treatment you choose. Don't hesitate to ask me or anyone on this board additional questions. PattyZ's willingness to share her experience on Temodar encouraged us to try it for my sister, and I'm so grateful to her for that.

[pattyz]

Emmay,
I'm so glad you saw Ragini's post. And, so very glad that your sister is still finding this combo successful. Her neuro onc is a blessing and brilliant, going outside the box of 'traditional' (minimally effective) treatments for bc brain mets.

big hugs to you,
gentle hugs to your sis,
pattyz xoxo

[Ragini]

Thanks to all of you for the inputs and/or words of encouragement. It was especially nice to hear from PattyZ after all this time. Hope you are doing well after all you went through previously.
After having looked around, Quadramet doesn't seem to be something which is very commonly used, and Sorafenib doesn't seem to have much application for bc as yet. So I'm leaning towards Doxil but am so worried about what it might do to my heart. The Muga's so far are looking OK, but that could change fast. I'm between the devil and deep blue sea......

Ragini

[pattyz]

Ragini,
When most/all 'other' commonly used tx's have been exausted, I feel that using any other tx with even anecdotal or small study/small response is worth trying... If (big if) quality of life is not too negatively effected. Hope you will have that good response to your next tx and hang on to some good QOL.

The universe has a strange sense of humor. As I have responded so well to my own tx's and have remained 'stable' for the past two yrs with my current 8 brain mets....

My 70 yr old partner of 17yrs was dx'd with Stage III locally advanced bc a month ago. He is doing TAC to try to shrink tumor enough for clear margins at surgery time.

Warm regards to Raj with warm hugs to you xoxo
patty

[Emmay]

PattyZ- a hopeful note for your partner:

Six or 7 yrs ago, in the early days of Herceptin trials, one of my children's teachers, in her 50s, was diagnosed with Stage 3b Her2+ bc. Her tumor was quite large, so they started with herceptin to shrink it as much as possible before surgery. The treatment was so effective that, during surgery, the surgeon could find no sign of the tumor.

The teacher followed up with AC+T, then radiation, and she has had no recurrence since.

[pattyz]

Thank you, sweetie...

At this point he is not Her2+++ but highly er+ and pr+ (90%-45%) so, looking at a 70% chance of responding well to Tamoxifen...when we can get to that point.

I was dx'd at age 50, with Stage IIIb, Inflammatory and Invasive with 2 tumors, (plus 6+nodes of 26 at surgery) Jan 8, 2000. Lyle has been my best bud throughout my journey, always there for me in any way I've needed. Now it's my turn to go to bat for him.

xoxopatty

[Believe51]

Another post I am pulling up so I can find it as an easy reference. Don't mean to be a pain.>>Believe51

Sometimes Ill see a book, and find it I already own it; its the same book, but in the new releases section with a new cover. How come publishers do that? Is it to help the book sell better?

[Believe51]

Is the information updated in those books? Sometimes another printing is a way to freshen up a cover or to update valuable information. I try to keep a list of books that I am own to help when I go shopping. Of course this is something of a challenge because I own my own library>>Believe51

[Believe51]

Excuse another bump my Sweeties, mind going a mile a minute and I am bumping between screens and legal pads right now...>>Believe51