Hi,
I had a Head & Neck CT scan and a follow up visit with my oncologist on January 5th. The radiology report was finalized today and all systems are clear. No new evidence of disease and my anatomy, when compared to my last CT scan in June, appears stable. So, all good news.
On the subject of improving my speech and swallowing functions (see background from December 2 2010 blog entry), the news is disappointing. I visited with my reconstructive surgeon and his physician assistant on January 3rd. It had been over three years since I had last seen him. We spent a very high quality hour together going over my options. I won't get into the detail here, they are just not that interesting to anyone but me. The bottom line was... make the best of what I have; surgical treatment is not a viable option due to the treatment risk of performing surgery in an irradiated area. In early December I was in touch with the UC Davis physician who did the implant on the head and neck cancer patient in Uruguay to help with his swallowing function. I may still schedule a consultation with him, but I have to be cautious. For me, even a minor surgery in an irradiated area may lead to long term disastrous complications.
Happy 2011. Stay healthy.
Ed
Friday, January 7, 2011
Monday, December 13, 2010
December 13 2010 – My Cancerversary
Hi Out There!
4 years ago today my doctor suggested palliative care as a treatment option. Well, I'm still here. Some days that surprises even me. I'm 3 years and 2 months with no evidence of disease (NED) and my current status as of last December moved from NED to "clinical remission."
- The profession of oncology got its start based on the observation of the effects of mustard gas in WW I. This seems highly ironic.
- Ether, the first anesthetic, was not in use until the late 1800s. Mastectomies have been documented back to 500 B.C. I think back to all those poor women.
- If we don’t kill the tumor, we kill the patient. This short simple statement reflects why cancer doctors and researchers take such an aggressive treatment approach. You may have to read it a few times to get its full meaning.
- The pap smear was named after George Papanicolaous, a Greek cytologist at Cornell University. He began human trials in the late 1920s. It wasn’t until 30 years later that his earlier discovery began to become a mainstream cancer prevention procedure. For most of his career, he was ridiculed and ignored by his peers as discovering a useless procedure. The ironies in the book abound.
- The cancer genome project is in progress and is focused on mapping every cancer gene in every type of cancer. When complete it is estimated to be 10,000 times the size of the human genome project.
- We are winning the war on cancer; it just so happens to be a very long and complicated march.
I'd like to take this opportunity to thank my friends, family, physicians, and researchers for their continued support and effort. It feels good to be celebrating my Cancerversary today.
Take care everyone and Happy Holidays.
Thursday, December 2, 2010
Swallowing Difficulties
The technical term for swallowing difficulties is dysphagia. My diagnosis, based on the results of a fluoroscope test interpreted by a highly trained speech therapist is severe dysphagia. I've written about this in my blog many times as it is the bane of my existence. I am continuing my quest to not just live with this issue, but to somehow fix it. This is partly due to wanting a better life for myself (who doesn't) and partly due to a case of OCD. I have trouble adjusting to things that are broken. In my case, my throat is broken and my ability to truly adapt to it wavers from partial acceptance to "just not going to take it anymore."
I came across an article yesterday (12/1/10) that caught my attention. A Uruguayan physician who is also a oral cancer survivor designed a small very simple implant which has allowed him to drink orally (versus a feeding tube) for the first time in 2 years. The operation was performed in a 45 minute procedure by two UC Davis physicians. Here's a link to the article.
http://www.healthcanal.com/surgery-rehabilitation/12808-Davis-surgeons-test-innovative-device-patient-with-swallowing-disorder.html
What caught my attention was the simplicity of the solution. It is not a panacea for all swallowing issues, but it could help thousands of people quickly and at a low cost. This may allow the patient in this article to live without a feeding tube. The estimated cost (based on other articles I have read) of a feeding tube per patient is $31,000 annually in medical expenses.
For myself, there are four separate issues which have lead to my diagnosis of severe dysphagia.
1) A dime sized hole in my soft palate which prohibits the ability of my swallowing function to create a proper vacuum (or suction) during the swallowing process,
2) Removal of part of my epiglottis which, if it were all there, would protect my airway during swallowing,
3) Removal of tongue and throat nerves which, when intact, help control muscles that make swallowing possible, and
4) Scaring in my upper esophagus (a result of radiation, chemo, and surgery) which have fused parts of my anatomy together that would, under normal circumstances, be working synergisticly and independently.
Here's my plan. First, I'm looking at options for patching the hole in my soft palette (issue #1 above). The Mayo Clinic is doing some leading edge work with Transoral Robotic Surgery for Oral Cancer. I plan to contact them as well as my own cancer center to explore options in this area. Second, I'll be reaching out to the physicians noted in the above article to explore the appropriateness and possibility of a device and operation similar to the one described in the article. This could address above issues #3 and #4. Issue #2, patching my epiglottis, is very unique to my particular situation. For that, I'll consult with my network of health care providers.
Although I began focusing on this set of potentially corrective actions yesterday, I view the exploration of this taking place over a six month time frame. Hey, Rome wasn't built in a day and the same can be said for what it might take to address my swallowing disorder.
Take care everyone.
Ed
I came across an article yesterday (12/1/10) that caught my attention. A Uruguayan physician who is also a oral cancer survivor designed a small very simple implant which has allowed him to drink orally (versus a feeding tube) for the first time in 2 years. The operation was performed in a 45 minute procedure by two UC Davis physicians. Here's a link to the article.
http://www.healthcanal.com/surgery-rehabilitation/12808-Davis-surgeons-test-innovative-device-patient-with-swallowing-disorder.html
What caught my attention was the simplicity of the solution. It is not a panacea for all swallowing issues, but it could help thousands of people quickly and at a low cost. This may allow the patient in this article to live without a feeding tube. The estimated cost (based on other articles I have read) of a feeding tube per patient is $31,000 annually in medical expenses.
For myself, there are four separate issues which have lead to my diagnosis of severe dysphagia.
1) A dime sized hole in my soft palate which prohibits the ability of my swallowing function to create a proper vacuum (or suction) during the swallowing process,
2) Removal of part of my epiglottis which, if it were all there, would protect my airway during swallowing,
3) Removal of tongue and throat nerves which, when intact, help control muscles that make swallowing possible, and
4) Scaring in my upper esophagus (a result of radiation, chemo, and surgery) which have fused parts of my anatomy together that would, under normal circumstances, be working synergisticly and independently.
Here's my plan. First, I'm looking at options for patching the hole in my soft palette (issue #1 above). The Mayo Clinic is doing some leading edge work with Transoral Robotic Surgery for Oral Cancer. I plan to contact them as well as my own cancer center to explore options in this area. Second, I'll be reaching out to the physicians noted in the above article to explore the appropriateness and possibility of a device and operation similar to the one described in the article. This could address above issues #3 and #4. Issue #2, patching my epiglottis, is very unique to my particular situation. For that, I'll consult with my network of health care providers.
Although I began focusing on this set of potentially corrective actions yesterday, I view the exploration of this taking place over a six month time frame. Hey, Rome wasn't built in a day and the same can be said for what it might take to address my swallowing disorder.
Take care everyone.
Ed
Sunday, October 31, 2010
The Cancer Sleeper Cell
I continue to read about cancer; my type of cancer and cancers in general. I have four primary sources: 1) The daily Wall Street Journal, 2) The Sunday New York Times, 3) friends/family who send me articles, and 4) Google alerts. For those not familiar with Google alerts, it is a Google feature which allows one to set up specific searches to run continuously, daily, or weekly for subjects in which one has an interest. This is where I find most of my cancer-related reading materials. For more information on Google Alerts, just google it.
Today's Sunday New York Times Magazine section had a fascinating research-oriented articles on cancer stem cells, "The Cancer Sleeper Cell." It's a long article, but provided added insight into my understanding of how important it would be to fighting relapses if one could identify, isolate, and destroy the cancer stem cell. What the article highlighted for me was that researchers believe that only one bad cell in a million bad cancer leukemia (a blood cancer) cells is a stem cell which can cause a relapse. The hypothesis being that if they can kill that one cell in a million, they can stop the cancer from relapsing. They were able to take this finding and apply it to various solid tumors. It also raised other important questions about what defines a cure and how to measure a treatment's success.
I was able to Google the article and the link is...
http://www.nytimes.com/2010/10/31/magazine/31Cancer-t.html
For those that are interested, enjoy this somewhat intellectually challenging reading. Take care everyone.
Ed
Today's Sunday New York Times Magazine section had a fascinating research-oriented articles on cancer stem cells, "The Cancer Sleeper Cell." It's a long article, but provided added insight into my understanding of how important it would be to fighting relapses if one could identify, isolate, and destroy the cancer stem cell. What the article highlighted for me was that researchers believe that only one bad cell in a million bad cancer leukemia (a blood cancer) cells is a stem cell which can cause a relapse. The hypothesis being that if they can kill that one cell in a million, they can stop the cancer from relapsing. They were able to take this finding and apply it to various solid tumors. It also raised other important questions about what defines a cure and how to measure a treatment's success.
I was able to Google the article and the link is...
http://www.nytimes.com/2010/10/31/magazine/31Cancer-t.html
For those that are interested, enjoy this somewhat intellectually challenging reading. Take care everyone.
Ed
Monday, October 11, 2010
Cutting Time and Cost in the Clinical Drug Approval Process Cycle
In my readings about and discussions with cancer researchers, it is clear that the cost of bringing a new drug to market (almost one billion dollars) and the elapse time of 5 plus years at minimum is costing countless lives and untold billions of dollars. The following article printed in the WSJ on 10/2/10, "A New Rx for Medicine" caught my attention.
http://online.wsj.com/article/SB10001424052748703882404575520190576846812.html#articleTabs%3Darticle
The claim is that through personal genetic understanding and this novel approach to testing multiple drugs simultaneously, they can learn as much in 6 months as would be possible to learn in 5 years under current standard testing protocols. To me, this approach is a breakthrough. For ease of reference, the text of the article follows. Be forewarned, it is a long article, but well worth reading.
A New Rx for Medicine
Fed up with slow drug trials, cancer patients and doctors are testing a fast track to personalized treatments.
When 37-year-old Kerry Landreth discovered a lump in her breast last April, she was told it would take three weeks to get a doctor's appointment to have it checked.
"I don't do three weeks," she recalls saying. "How about today?"
By the end of the day, she had talked her way into a doctor's appointment, a mammogram and a biopsy to determine whether the suspicious lump was a tumor. A few days later came the diagnosis: stage 2 invasive ductal breast cancer, a particularly aggressive form of the disease. When a surgeon recommended a double mastectomy, she decided to consider other options.
Now, Ms. Landreth, a vice president at the San Francisco office of a Wall Street investment bank and the mother of two young children, is among the first participants in a novel clinical trial that is similarly impatient with the status quo in cancer treatment.
The trial, called I-Spy 2, employs several innovative approaches to improve the notoriously slow and inefficient process of developing new cancer drugs. Using the latest advances in genetics, I-Spy 2 aims to match experimental drugs with the molecular makeup of tumors most likely to respond to them. And it tests multiple drugs at once, with the intent of getting the most effective ones into late-stage trials more quickly.
The goal is to reverse a dismal record, in which 60% to 70% of late-stage cancer studies fail, and to dramatically reduce the time and cost required to get promising new drugs to the market. Currently it can take $1 billion, thousands of patients and more than a decade to gather the evidence necessary to approve a new cancer drug.
Kerry Landreth just finished her final round ofchemotherapy.
"Predictability is the Holy Grail here—being able to identify promising drug candidates early and figuring out who they might work in," says Janet Woodcock, director of the Center for Drug Evaluation and Research at the U.S. Food and Drug Administration.
The new trial draws from a growing body of research showing that the genetic makeup of tumors varies widely even among patients diagnosed with the same cancer. Some of these molecular traits, called biomarkers, make a tumor vulnerable to a specific medicine, while others may thwart a drug's effect.
A big part of the problem with conventional trials is that they essentially take all comers. Researchers know many participants won't benefit from the treatment. Those who don't respond can cause a drug to fail even though a significant minority of patients might benefit.
"Unless we do something different, people are going to give up on doing trials" for cancer, says Laura Esserman, director of the breast-care center at University of California, San Francisco, and co-leader of I-Spy 2.
The study focuses on women with aggressive breast cancers that have not spread to other organs. It aims to collect information about experimental drugs that would then enable drug companies to design leaner, faster late-stage trials that enroll only patients whose tumors had a high probability of responding to the treatment. Those trials, called phase III trials, provide critical data used in determining whether a drug will be approved.
"The vision is a 300-patient phase III trial instead of a 3,000-patient trial, with better results," says Don Berry, head of Quantitative Sciences at M.D. Anderson Cancer Center in Houston and co-leader of the study.
I-Spy 2's effort to bring much higher standards of productivity to cancer-drug development is inspired partly by Dr. Esserman's experience at business school. In addition to her surgical training, she has an MBA from Stanford University, where she learned about the rapid pace of innovation in high-tech industries. She was particularly influenced by the idea of what Intel Corp. chairman Andrew Grove calls "knowledge turns"—breakthroughs that have led to annual advances in microchip technology and an ongoing revolution in the performance of products like personal computers.
In the development of cancer drugs, by contrast, "knowledge turns" may take 10 or 15 years. Typically treatments are first studied in metastatic patients—for whom cancer has spread from the original tumor site to other parts of the body—who didn't benefit from standard therapies. Even when drugs succeed, benefits often are limited to a few extra weeks or months of life. Then it takes several more years to test successful drugs in early-stage patients, for whom effective treatments could mean a cure.
"We have 45,000 women dying each year of breast cancer," Dr. Esserman says. "We should be compelled to move faster."
About 3½ years ago, she joined forces with Dr. Berry at M.D. Anderson, an expert in a new approach to clinical trials called "adaptive design," to plan I-Spy 2. Unlike conventional trials, in which no one sees results until the end, "we look at the data right away," Dr. Berry says. What is learned in the early going helps to determine which drugs are assigned to patients later in the study, speeding the emergence of winners and losers.
The trial incorporates other new approaches. It's currently testing five drugs at once from three different companies. As compounds graduate to phase III studies or are winnowed out for lack of significant benefit, new candidates are cycled in, sparing the cost and time to mount separate trials. Up to 12 candidates will be screened over the course of the study.
In addition, participants get a six-month course of chemotherapy before having an operation to remove their tumors. In many studies, surgery is performed first, followed by chemotherapy and radiation, reflecting a long-standing preference to quickly remove tumors before beginning drug treatment. As a result, it can take three to five years to determine whether a drug is working, as researchers wait to see if the cancer recurs. Whether surgery occurs before or after chemo does not affect long-term outcomes.
In I-Spy 2, researchers use an MRI to evaluate a tumor's response to a drug early in the trial and get a definitive answer at surgery. "All of a sudden I've taken a five-year learning curve and shortened it to six months," Dr. Esserman says.
Ms. Landreth's ordeal began with a heavy sensation in her left breast that led her to discover the lump. It seemed to come out of nowhere and felt as big and hard as a marble. The news that she had cancer came while she was on a business trip to Los Angeles. "It was a shocker," she says.
She didn't reject out of hand the surgeon's recommendation of a double mastectomy, but as she and her husband, Creighton Reed, cast a net among friends for advice, Dr. Esserman's name kept coming up. They were taken with her on their first meeting.
"She sweeps into the room like this Fleetwood Mac figure," Ms. Landreth says, referring to Dr. Esserman's resemblance to the group's singer Stevie Nicks. "There's no B.S. She cuts completely to the facts. She gives you a hug at the end. You leave thinking, 'All right, I can do this.'"
A key feature of the study is a molecular analysis that determines whether the participants' tumors are positive or negative for estrogen, progesterone and the Her2 protein—the basis for putting patients in one of 10 biomarker categories.
Every patient gets 12 weekly treatments with the standard chemotherapy taxol, followed by four biweekly infusions of the standard drugs Adriamycin and Cytoxan. A precursor study called I-Spy 1 showed that 30% of patients who got that regimen saw their tumors disappear completely.
About 80% of patients are also randomly assigned to one of five experimental agents (from Abbott Laboratories, Amgen Inc. and Pfizer Inc.), given with the taxol treatments. Each drug targets a different molecular pathway affecting the growth and proliferation of tumors.
Tumor response is assessed from MRIs and at the time of surgery after chemo is completed. The associations between tumor response and patient biomarkers among the early participants will influence how subsequent patients are assigned to the treatments.
"The goal is to pair drug and biomarker signatures and graduate them into a small phase III trial that has gotten rid of the subset of patients that don't benefit," says Dr. Berry.
There are challenges. Though biomarkers are a promising predictor of a drug's effectiveness, tumor response to a drug can vary widely despite biomarker status. Doctors say that more evidence is needed linking biomarkers to long-term outcomes.
Eric Winer, the director of breast oncology at Dana-Farber Cancer Institute in Boston, is not involved with I-Spy. He calls it "a very good trial," but he wonders if the bar is set too high. "We have to be very careful not to toss away drugs prematurely based on their failure to pass this screen," he says.
The bar is high, Dr. Esserman acknowledges, but the study isn't after incremental improvement. "This trial will say who are the big winners," she says.
Even if I-Spy 2 succeeds in showing that compounds have a high probability of success in small late-stage studies, it isn't clear yet whether or how the FDA's regulatory system would then enable faster drug approval. "That's our next step," Dr. Esserman says.
The study, to cost $25 million over five years, is sponsored by the Biomarkers Consortium, a public-private partnership managed by the Foundation for the National Institutes of Health. It includes representatives from the National Cancer Institute, the FDA and the pharmaceutical industry. Funders include the Safeway Foundation, UCSF, Quantum Leap Health Care Collaborative and several drug companies. So far, about 20 patients are enrolled, with the expectation that about 800 will participate at some 20 medical centers across the U.S.
Ms. Landreth was assigned to one of the experimental drugs and began treatment on May 18. By the second week, a physical check of her tumor suggested it had shrunk notably after just a single treatment. In one of what became weekly email updates to friends, she wrote: "I have always liked to get good grades, so the nerd in me was fully flourishing when the cancer nurse said she was 'over the moon' about how I'm responding to the drugs."
The next Tuesday, as she awaited her third round of chemo, she wrote: "I got in trouble with my chemo nurse for trying to tough it out this weekend. I didn't think that a 70 min walk, 18 holes of golf (I broke 100) and a little too much heat + a total failure to use the nausea drugs would cause a problem.... oops!" The result, she wrote, was almost unremitting vomiting for 36 hours.
But, she added, the tumor had shrunk dramatically again.
Later that week, an MRI confirmed the progress. After just three weeks, her tumor had shrunk more than 50%, a strong predictor, Dr. Esserman told her, that the tumor would be gone by the end of chemotherapy.
Still, the cumulative effect of the chemo exacted a toll on Ms. Landreth. She lost her hair, shaving it all off just days before her 37th birthday. Frequent nausea posed a persistent challenge to her energy and appetite. At one point, Hope Rugo, her oncologist, warned that she'd lost too much weight, information she disclosed in an update titled, "Bring on the guacamole."
By week eight, her tumor was the size of a watermelon seed, compared with a golf ball the day she enrolled. At week 12, it was the size of a sesame seed. Her medical team was ecstatic. "There's nothing like hearing them cheer," she says.
Not everyone sees tumors melt away. Inne Harry-Ogaree, 54, who entered the trial at about the same time as Ms. Landreth, had her tumor grow despite treatment with taxol and an experimental drug. She was switched to a more standard regimen, which has shrunk the tumor by more than 50%. "It hasn't been easy," Ms. Harry-Ogaree says. "But I have a positive attitude toward my treatment and my care."
Ms. Landreth's final chemo session was last Tuesday. Under the study protocol, she'll undergo surgery in November. The actual status of her tumor won't be known until then.
Three weeks into the trial, she got the results of a test for mutations in the BRCA1 and BRCA2 genes. Dr. Esserman suggested the test because of a family history of ovarian and prostate cancers. The test was positive for BRCA2, putting Ms. Landreth's lifetime risk of another bout with breast cancer as high as 85%; for ovarian cancer, it's 30%.
She knew immediately what her surgical plan would be: the double mastectomy that she had initially resisted. She plans to have her ovaries removed as well.
Ms. Landreth's results will go into the trial database and could affect which other patients are assigned to the drug. If it turns out, as Dr. Esserman expects, that her tumor is gone, she is unlikely to need radiation.
In her email update early this week, she expressed "high hopes" that surgery would reveal her to be "cancer-free." Reflecting both the challenge of the surgery ahead and the battle she has already fought, she wrote: "I have to remember that after 16 rounds of magic poison it is going to take awhile to bounce back, no matter how fierce my determination. Churchill apparently said, '[If] you are going through hell, keep going!'"
Write to Ron Winslow at ron.winslow@wsj.com
http://online.wsj.com/article/SB10001424052748703882404575520190576846812.html#articleTabs%3Darticle
The claim is that through personal genetic understanding and this novel approach to testing multiple drugs simultaneously, they can learn as much in 6 months as would be possible to learn in 5 years under current standard testing protocols. To me, this approach is a breakthrough. For ease of reference, the text of the article follows. Be forewarned, it is a long article, but well worth reading.
A New Rx for Medicine
Fed up with slow drug trials, cancer patients and doctors are testing a fast track to personalized treatments.
When 37-year-old Kerry Landreth discovered a lump in her breast last April, she was told it would take three weeks to get a doctor's appointment to have it checked.
"I don't do three weeks," she recalls saying. "How about today?"
By the end of the day, she had talked her way into a doctor's appointment, a mammogram and a biopsy to determine whether the suspicious lump was a tumor. A few days later came the diagnosis: stage 2 invasive ductal breast cancer, a particularly aggressive form of the disease. When a surgeon recommended a double mastectomy, she decided to consider other options.
Now, Ms. Landreth, a vice president at the San Francisco office of a Wall Street investment bank and the mother of two young children, is among the first participants in a novel clinical trial that is similarly impatient with the status quo in cancer treatment.
The trial, called I-Spy 2, employs several innovative approaches to improve the notoriously slow and inefficient process of developing new cancer drugs. Using the latest advances in genetics, I-Spy 2 aims to match experimental drugs with the molecular makeup of tumors most likely to respond to them. And it tests multiple drugs at once, with the intent of getting the most effective ones into late-stage trials more quickly.
The goal is to reverse a dismal record, in which 60% to 70% of late-stage cancer studies fail, and to dramatically reduce the time and cost required to get promising new drugs to the market. Currently it can take $1 billion, thousands of patients and more than a decade to gather the evidence necessary to approve a new cancer drug.
Kerry Landreth just finished her final round ofchemotherapy.
"Predictability is the Holy Grail here—being able to identify promising drug candidates early and figuring out who they might work in," says Janet Woodcock, director of the Center for Drug Evaluation and Research at the U.S. Food and Drug Administration.
The new trial draws from a growing body of research showing that the genetic makeup of tumors varies widely even among patients diagnosed with the same cancer. Some of these molecular traits, called biomarkers, make a tumor vulnerable to a specific medicine, while others may thwart a drug's effect.
A big part of the problem with conventional trials is that they essentially take all comers. Researchers know many participants won't benefit from the treatment. Those who don't respond can cause a drug to fail even though a significant minority of patients might benefit.
"Unless we do something different, people are going to give up on doing trials" for cancer, says Laura Esserman, director of the breast-care center at University of California, San Francisco, and co-leader of I-Spy 2.
The study focuses on women with aggressive breast cancers that have not spread to other organs. It aims to collect information about experimental drugs that would then enable drug companies to design leaner, faster late-stage trials that enroll only patients whose tumors had a high probability of responding to the treatment. Those trials, called phase III trials, provide critical data used in determining whether a drug will be approved.
"The vision is a 300-patient phase III trial instead of a 3,000-patient trial, with better results," says Don Berry, head of Quantitative Sciences at M.D. Anderson Cancer Center in Houston and co-leader of the study.
I-Spy 2's effort to bring much higher standards of productivity to cancer-drug development is inspired partly by Dr. Esserman's experience at business school. In addition to her surgical training, she has an MBA from Stanford University, where she learned about the rapid pace of innovation in high-tech industries. She was particularly influenced by the idea of what Intel Corp. chairman Andrew Grove calls "knowledge turns"—breakthroughs that have led to annual advances in microchip technology and an ongoing revolution in the performance of products like personal computers.
In the development of cancer drugs, by contrast, "knowledge turns" may take 10 or 15 years. Typically treatments are first studied in metastatic patients—for whom cancer has spread from the original tumor site to other parts of the body—who didn't benefit from standard therapies. Even when drugs succeed, benefits often are limited to a few extra weeks or months of life. Then it takes several more years to test successful drugs in early-stage patients, for whom effective treatments could mean a cure.
"We have 45,000 women dying each year of breast cancer," Dr. Esserman says. "We should be compelled to move faster."
About 3½ years ago, she joined forces with Dr. Berry at M.D. Anderson, an expert in a new approach to clinical trials called "adaptive design," to plan I-Spy 2. Unlike conventional trials, in which no one sees results until the end, "we look at the data right away," Dr. Berry says. What is learned in the early going helps to determine which drugs are assigned to patients later in the study, speeding the emergence of winners and losers.
The trial incorporates other new approaches. It's currently testing five drugs at once from three different companies. As compounds graduate to phase III studies or are winnowed out for lack of significant benefit, new candidates are cycled in, sparing the cost and time to mount separate trials. Up to 12 candidates will be screened over the course of the study.
In addition, participants get a six-month course of chemotherapy before having an operation to remove their tumors. In many studies, surgery is performed first, followed by chemotherapy and radiation, reflecting a long-standing preference to quickly remove tumors before beginning drug treatment. As a result, it can take three to five years to determine whether a drug is working, as researchers wait to see if the cancer recurs. Whether surgery occurs before or after chemo does not affect long-term outcomes.
In I-Spy 2, researchers use an MRI to evaluate a tumor's response to a drug early in the trial and get a definitive answer at surgery. "All of a sudden I've taken a five-year learning curve and shortened it to six months," Dr. Esserman says.
Ms. Landreth's ordeal began with a heavy sensation in her left breast that led her to discover the lump. It seemed to come out of nowhere and felt as big and hard as a marble. The news that she had cancer came while she was on a business trip to Los Angeles. "It was a shocker," she says.
She didn't reject out of hand the surgeon's recommendation of a double mastectomy, but as she and her husband, Creighton Reed, cast a net among friends for advice, Dr. Esserman's name kept coming up. They were taken with her on their first meeting.
"She sweeps into the room like this Fleetwood Mac figure," Ms. Landreth says, referring to Dr. Esserman's resemblance to the group's singer Stevie Nicks. "There's no B.S. She cuts completely to the facts. She gives you a hug at the end. You leave thinking, 'All right, I can do this.'"
A key feature of the study is a molecular analysis that determines whether the participants' tumors are positive or negative for estrogen, progesterone and the Her2 protein—the basis for putting patients in one of 10 biomarker categories.
Every patient gets 12 weekly treatments with the standard chemotherapy taxol, followed by four biweekly infusions of the standard drugs Adriamycin and Cytoxan. A precursor study called I-Spy 1 showed that 30% of patients who got that regimen saw their tumors disappear completely.
About 80% of patients are also randomly assigned to one of five experimental agents (from Abbott Laboratories, Amgen Inc. and Pfizer Inc.), given with the taxol treatments. Each drug targets a different molecular pathway affecting the growth and proliferation of tumors.
Tumor response is assessed from MRIs and at the time of surgery after chemo is completed. The associations between tumor response and patient biomarkers among the early participants will influence how subsequent patients are assigned to the treatments.
"The goal is to pair drug and biomarker signatures and graduate them into a small phase III trial that has gotten rid of the subset of patients that don't benefit," says Dr. Berry.
There are challenges. Though biomarkers are a promising predictor of a drug's effectiveness, tumor response to a drug can vary widely despite biomarker status. Doctors say that more evidence is needed linking biomarkers to long-term outcomes.
Eric Winer, the director of breast oncology at Dana-Farber Cancer Institute in Boston, is not involved with I-Spy. He calls it "a very good trial," but he wonders if the bar is set too high. "We have to be very careful not to toss away drugs prematurely based on their failure to pass this screen," he says.
The bar is high, Dr. Esserman acknowledges, but the study isn't after incremental improvement. "This trial will say who are the big winners," she says.
Even if I-Spy 2 succeeds in showing that compounds have a high probability of success in small late-stage studies, it isn't clear yet whether or how the FDA's regulatory system would then enable faster drug approval. "That's our next step," Dr. Esserman says.
The study, to cost $25 million over five years, is sponsored by the Biomarkers Consortium, a public-private partnership managed by the Foundation for the National Institutes of Health. It includes representatives from the National Cancer Institute, the FDA and the pharmaceutical industry. Funders include the Safeway Foundation, UCSF, Quantum Leap Health Care Collaborative and several drug companies. So far, about 20 patients are enrolled, with the expectation that about 800 will participate at some 20 medical centers across the U.S.
Ms. Landreth was assigned to one of the experimental drugs and began treatment on May 18. By the second week, a physical check of her tumor suggested it had shrunk notably after just a single treatment. In one of what became weekly email updates to friends, she wrote: "I have always liked to get good grades, so the nerd in me was fully flourishing when the cancer nurse said she was 'over the moon' about how I'm responding to the drugs."
The next Tuesday, as she awaited her third round of chemo, she wrote: "I got in trouble with my chemo nurse for trying to tough it out this weekend. I didn't think that a 70 min walk, 18 holes of golf (I broke 100) and a little too much heat + a total failure to use the nausea drugs would cause a problem.... oops!" The result, she wrote, was almost unremitting vomiting for 36 hours.
But, she added, the tumor had shrunk dramatically again.
Later that week, an MRI confirmed the progress. After just three weeks, her tumor had shrunk more than 50%, a strong predictor, Dr. Esserman told her, that the tumor would be gone by the end of chemotherapy.
Still, the cumulative effect of the chemo exacted a toll on Ms. Landreth. She lost her hair, shaving it all off just days before her 37th birthday. Frequent nausea posed a persistent challenge to her energy and appetite. At one point, Hope Rugo, her oncologist, warned that she'd lost too much weight, information she disclosed in an update titled, "Bring on the guacamole."
By week eight, her tumor was the size of a watermelon seed, compared with a golf ball the day she enrolled. At week 12, it was the size of a sesame seed. Her medical team was ecstatic. "There's nothing like hearing them cheer," she says.
Not everyone sees tumors melt away. Inne Harry-Ogaree, 54, who entered the trial at about the same time as Ms. Landreth, had her tumor grow despite treatment with taxol and an experimental drug. She was switched to a more standard regimen, which has shrunk the tumor by more than 50%. "It hasn't been easy," Ms. Harry-Ogaree says. "But I have a positive attitude toward my treatment and my care."
Ms. Landreth's final chemo session was last Tuesday. Under the study protocol, she'll undergo surgery in November. The actual status of her tumor won't be known until then.
Three weeks into the trial, she got the results of a test for mutations in the BRCA1 and BRCA2 genes. Dr. Esserman suggested the test because of a family history of ovarian and prostate cancers. The test was positive for BRCA2, putting Ms. Landreth's lifetime risk of another bout with breast cancer as high as 85%; for ovarian cancer, it's 30%.
She knew immediately what her surgical plan would be: the double mastectomy that she had initially resisted. She plans to have her ovaries removed as well.
Ms. Landreth's results will go into the trial database and could affect which other patients are assigned to the drug. If it turns out, as Dr. Esserman expects, that her tumor is gone, she is unlikely to need radiation.
In her email update early this week, she expressed "high hopes" that surgery would reveal her to be "cancer-free." Reflecting both the challenge of the surgery ahead and the battle she has already fought, she wrote: "I have to remember that after 16 rounds of magic poison it is going to take awhile to bounce back, no matter how fierce my determination. Churchill apparently said, '[If] you are going through hell, keep going!'"
Write to Ron Winslow at ron.winslow@wsj.com
Tuesday, August 3, 2010
Another Potential Weapon Against Head and Neck Cancer
Herpes - the gift that keeps on giving. A phase I/II study completed by BioVex was just published in ASCO (American Society of Clinical Oncology). By injecting a genetically altered form of the Herpes virus directly into the lymph nodes of 17 patients with head and neck cancer in combination with Cisplatin and radiation, head and neck tumour shrinkage could be seen on scans for 14 patients (82.3%), while 93 per cent of patients had no trace of residual cancer in their lymph nodes when subsequently surgically removed. After an average follow-up time of 29 months (19 to 40 months), 82.4 per cent of patients remained alive. Only two of 13 patients given the top virus treatment dose relapsed, and no patient had recurrent loco-regional disease.
Dr Robert Coffin, Founder and Chief Technology Officer, for BioVex, said: “Up to half of patients given the current standard treatment of chemotherapy combined with radiotherapy typically relapse within two years, following which the prognosis is grim, so these results compare very favorably. This, combined with the very high complete pathological response rate indicates that OncoVEX may provide significant additional clinical benefit to chemotherapy and radiotherapy alone, hence our decision to move directly to a pivotal Phase III trial."
Speaking from a personal experience perspective, this is a potential game changer. After 36 IMRT radiation treatments which ended in July of 2005, they found live squamous cell carcinoma cells in 2 of the 17 lymph nodes removed from my left neck. Within 18 months following the radiation treatments, I had 4 local recurrences which lead to five surgeries one of which was a 12 hour salvage surgery which has left me permanently disabled. I spent almost two years in bed due to the debilitating effects of nine different chemotherapy regimens. All of this saved my life, but the side effects, using Dr. Coffin's word, have been grim. I am currently in remission and have had no evidence of disease for 34 months. I continue to take a maintenance chemo drug and will do so as long as the side effects from that drug are minimal. I have no proof of this, but I suspect the maintenance drug is keeping my cancer from returning.
I wonder at times how my life would have been different if the above treatment had been available to me 5 years ago. This treatment along with others I have written about recently gives me hope that others will not have to travel down my path. For those of you wondering, I was neither a smoker or a drinker. My disease was not related to the HPV virus. Where it came from is a mystery.
Here are two links to articles on the above clinical trial.
http://www.businesswire.com/portal/site/home/permalink/?ndmViewId=news_view&newsId=20100802005515&newsLang=en
http://www.aolhealth.com/2010/08/02/herpes-a-new-weapon-against-cancer/
Take care everyone.
Dr Robert Coffin, Founder and Chief Technology Officer, for BioVex, said: “Up to half of patients given the current standard treatment of chemotherapy combined with radiotherapy typically relapse within two years, following which the prognosis is grim, so these results compare very favorably. This, combined with the very high complete pathological response rate indicates that OncoVEX may provide significant additional clinical benefit to chemotherapy and radiotherapy alone, hence our decision to move directly to a pivotal Phase III trial."
Speaking from a personal experience perspective, this is a potential game changer. After 36 IMRT radiation treatments which ended in July of 2005, they found live squamous cell carcinoma cells in 2 of the 17 lymph nodes removed from my left neck. Within 18 months following the radiation treatments, I had 4 local recurrences which lead to five surgeries one of which was a 12 hour salvage surgery which has left me permanently disabled. I spent almost two years in bed due to the debilitating effects of nine different chemotherapy regimens. All of this saved my life, but the side effects, using Dr. Coffin's word, have been grim. I am currently in remission and have had no evidence of disease for 34 months. I continue to take a maintenance chemo drug and will do so as long as the side effects from that drug are minimal. I have no proof of this, but I suspect the maintenance drug is keeping my cancer from returning.
I wonder at times how my life would have been different if the above treatment had been available to me 5 years ago. This treatment along with others I have written about recently gives me hope that others will not have to travel down my path. For those of you wondering, I was neither a smoker or a drinker. My disease was not related to the HPV virus. Where it came from is a mystery.
Here are two links to articles on the above clinical trial.
http://www.businesswire.com/portal/site/home/permalink/?ndmViewId=news_view&newsId=20100802005515&newsLang=en
http://www.aolhealth.com/2010/08/02/herpes-a-new-weapon-against-cancer/
Take care everyone.
Thursday, July 1, 2010
June 30 2010
Having had a little literary fun and a trip down memory lane in my last post dated April 29 2010, it is time to look to the present. I had my quarterly exam at the cancer center on June 30th. It began with blood work, a chest x-ray, and a head & neck CT scan. I visited with a speech therapist to discuss tongue exercises which may help with swallowing issues. Next I met with my oncologist and his physician assistant (PA). They had the finalized radiology report back from the CT scan I had two hours earlier. ALL CLEAR!!!! Both my doctor and his PA did a thorough exam. Again, all clear. That makes it 32 months with no evidence of disease and 6 months for clinical remission. I'm continuing on the daily maintenance chemo drug as the side effects are mild and the risk of a recurrence is still high. But, the further out I get, the smaller the odds of a recurrence. So, all good news. No qualifier.
On a random topic since I have your attention, I discovered a new source of entertainment on the world wide web. For those of you that enjoy music, give http://www.pandora.com/ a try. It is completely free and tailored to your specific tastes. Plug in a few artists whose music you enjoy and it does the rest. Non stop streaming music 24 x 7.
Take care. Ed.
On a random topic since I have your attention, I discovered a new source of entertainment on the world wide web. For those of you that enjoy music, give http://www.pandora.com/ a try. It is completely free and tailored to your specific tastes. Plug in a few artists whose music you enjoy and it does the rest. Non stop streaming music 24 x 7.
Take care. Ed.
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