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"I only know what has helped me cope and continue fighting. My doctor said it well. I overheard him telling his new partner that I have been "fierce in involving" myself in my own care, reading, researching and learning all I could..."

 "Tumors need blood to live. That is, tumors need the oxygen and nutrients brought by the blood...."

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Q & A:  A Clearity patient wants to know... more questions about Avastin

Clinical Trial Phases: What They Mean

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Fierce In Involving: Barbara's StoryFierce
by Barbara Sanders This December marks five years since my ovarian cancer diagnosis.  Just six months later the cancer recurred. Women who have traveled this road understand. Diagnosis is frightening. Recurrence is devastating. No one talks about cure anymore.
   
My journey has been filled with fear, frustration at how little advance we have seen in defeating this disease, and, at times, depression. It also has been a journey of  discovery and hope.   

I  have discovered more strength and grit than I ever thought possible and today I have more hope than at any time since my recurrence. After a number of surgeries, and a number of standard treatments that failed, a clinical trial saved my life. I am now on a monthly maintainence  of Avastin.
    
I have been fortunate to have an Oncologist who switched treatments quickly if they did  did not appear to be working. But how many heavily damaging treatments could I have avoided if I had been profiled earlier? The Clearity foundation is changing that for women who will follow me.
    
People have asked me why I think I'm still here fighting. They point out that I have family and friends who have loved and supported me throughout. They note my positive attitude. But many wonderful women with a lot of support, great attitudes and the will to live have died from this disease.
 
I only know what has helped me cope and continue fighting. My doctor said it well. I overheard him telling his new partner that I have been "fierce in involving" myself in my own care, reading, researching and learning all I could. I also have pushed myself out the door to hike on days when I didn't really feel like it, keeping myself strong. Marching up a mountain is like conquering the enemy.  I often thought of this battle as a goal post that kept moving on me. Sometimes I didn't know if I could move with it again.   But I have.  

Two years ago hope was fading. Now my doctors describe my disease as chronic, something to be managed. I can live with that for now. I feel  fortunate to be here.  But I will never give up on a cure.
Avastin: Choking off a tumor's blood supply routesAvastin
by Cory Bentley, Ph.D Tumors need blood to live. That is, tumors need the oxygen and nutrients brought by the blood. To ensure that that tumors get the blood supply they need, they send a molecular message directing the body to grow new blood vessels in the tumor. This new vessel growth is called angiogenesis or vascularization. The molecular command for angiogenesis is communicated by VEGF (vascular endothelial growth factor), a factor secreted by the tumor. By intervening in this chain of molecular commands, the drug called AvastinŽ can slow or reverse tumor vascularization.

Avastin is an antibody that binds specifically to VEGF and prevents it from interacting with its receptor. In this way, Avastin effectively blocks the signal sent by tumor cells to direct blood vessel growth.  Avastin has already been approved for lung, colon and breast cancer; however, for these other forms of cancer, Avastin is only effective when combined with more traditional chemotherapeutics such as carboplatin and paclitaxel, which are standard therapies for ovarian cancer.

The ineffectiveness of Avastin alone for some cancer patients has lead scientists to hypothesize that Avastin's anti-tumor effect requires more than simply stopping angiogenesis. Avastin may need additional tumor fighting activity through the addition of chemotherapy.  One theory advanced by Dr. David Cheresh, a leader in the tumor vascularization field, as well as others is the idea that Avastin may make tumors more sensitive to chemotherapeutics. One way this may happen is by promoting the effective delivery of chemotherapeutics to the tumors. The normal blood vessel pattern in the organs of the body is very organized like well planned city streets. Tumor vessels, on the other hand, are usually very disorganized: they meander here and there and are not especially efficient at distributing blood to all the parts of the tumor. The inhibition of VEGF will not only reduce the number of blood vessels, but may also promote a more organized vessel plan within the tumor.  Blood vessels become more organized when VEGF levels are lower. It is the difference between the city engineer saying, "Give me fifty streets ASAP," and, "Here is an organized plan to make 10 street to serve this area." By Avastin, creating a more "normalized" vasularization within the tumor, it may promote more efficient delivery of the anti-cancer chemotherapeutics to all parts of the tumor.

Much work is yet to be done to identify when Avastin will be effective and in combination with which chemotherapies.  Currently there are 36 ovarian cancer trials enrolling patients that involve Avastin as listed on the National Institutes of Health website of clinical trials (clinicaltrials.gov). According to a press release from Genentech, a recently completed Phase III trial of late stage ovarian cancer patients treated with carboplatin/paclitaxel and Avastin showed an improvement in progression-free survival. However, the extent of this "good news," the actual increase in progression-free survival time is not clear since the data has not yet been publicly released.

In addition, Avastin is not without side effects. For example, besides being involved in tumor angiogenesis, VEGF is important in angiogenesis required for wound healing, including the healing after surgery.  Patients should not take Avastin one month before and one month after surgery. Avastin has a number of other potential serious side effects including, severe hypertension, kidney malfunction, nervous system and vision disturbances, and infection. The ongoing clinical trials will help show under what circumstances Avastin may be effective and in what circumstances the benefits outweigh the costs associated with side effects. Gynecologic oncologists are encouraged by the identification of clear benefits of Avastin in other cancers. This signals hope for an Avastin benefit against ovarian cancer. Certainly, the number of trials indicates that the hope for Avastin in ovarian cancer is very high.
 
Q&A: A Clearity Patient Wants To Know...QA
by Barbara Sanders
More questions about Avastin


Q     If we already know that Avastin is approved to work in other cancers, why are there so many trials for ovarian cancer?

A     Avastin does not work in all cases. The effectiveness of Avastin could depend on which drugs it is combined with and the stage of the tumor. In addition, the most effective dose of Avastin and the duration of Avastin treatment are being tested in these trials.
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Q     We know that the protein involved in angiogenesis shows up in about 80% of patients, but only 30% of ovarian cancer patients are responding.  How do we know whether I will respond or not?

A     We don't know yet. However, academic research, results from clinical trials, and Clearity's own molecular profiling efforts may eventually help identify which patients are most likely to respond to Avastin therapy.
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Q     There was buzz on some of the blogs about "rebound," where patients took Avastin, then stopped taking it, and the cancer came back worse.  Should I be worried?

A     The potential for rebound after Avastin has nowhere the strength of evidence as the potential for Avastin to increase survival. There is a scant bit of scientific evidence of "rebound" after stopping Avastin. These were very small studies that looked at patients that clearly had residual tumors when treatment was halted. Clinical trials are attempting to address this potential issue using longer treatment times.

Clinical Trial Phases: What They MeanClinical
by Cory Bentley, Ph.D
ˇPhase I
-Tests the safety of the drug
-All volunteers are given the drug. There is no placebo group. These are dose escalating studies, meaning that the first patients receive the lowest dose of the drug. If there are not adverse reactions, the next group of patients will receive a higher dose and so on. Patients will also be monitored for tumor response.
-One to three locations involved.
-Twenty to 80 volunteers.
 
ˇPhase II
-Tests for efficacy (effect on cancer growth or recurrence) and the dosing requirements for efficacy
-There may or not be a placebo control group. The placebo group is not given the active drug, but rather an inert look-alike to control for effects not related to the active drug. The trial will specify whether or not there is a placebo group.
-There are usually several locations involved.  The precise locations for each clinical trial are listed on NIH's website:  www.clinicaltrials.gov.
-One hundred to 300 volunteers

ˇPhase III
-The definitive assessment of the effectiveness of a drug
-This trial will have a placebo control group.  These studies are double blind meaning that neither the patient nor the doctor knows if the drug is active or a placebo.
-Several hundred locations may be involved.
-One thousand to 3000 volunteers
 
 
Clearing a Path to a Cure,

The Clearity Foundation

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