Clinical Trial Update - After Cycles 19 and 20

Hi, All -

I flew down to St. Louis with my brother Dave on Monday to get the results of my latest CT scan.

Generally speaking, the results were good. There was some growth (less than 1 centimeter) in one of my smaller tumors, but the large tumor in my lung showed no growth and may have even shrunk a little. (I apparently breathed at the wrong moment and they couldn't get an accurate reading.)

The team in St. Louis are still pleased with the results and I'm classified as "stable". (That only applies to the disease, not emotionally, mentally, or any other way! ) They still say I'm reacting better to the drug than any of their other patients in the ST. Louis study location . That's good to hear, but I still feel really sorry for the patients with worse reactions!

The head of the study presented a preliminary report to a group in Canada earlier this month. It's interesting reading. If you want to look at it, go here.

I'll have my next scan in early November and will go to St. Louis on November 11 to get the results and pick up the next two cycles of Sutent.

Thanks for your continued prayers and support. On to Cycles 21 and 22!

John

P.S. I feel silly even mentioning this, but I have a blog with a collection of articles I find interesting. It's located at http://thyroidcancerfight.blogspot.com/.

P.P. S. Click here to read an interesting story about Pfizer, the maker of Sutent. It's good to know they're keeping on top of things in Washington!

Cancer Takes Aim At Thyroid

Cancer Takes Aim At Thyroid

USA Today

August 17, 2009

A medical mystery: As overall cancer rates fall, why are thyroid cancer rates rising? Diagnoses of cancer in this gland in the neck are increasing about 6% a year, faster than cancers found anywhere else, according to one National Cancer Institute analysis.

Researchers know one big reason: The many medical scans Americans have, for everything from neck pain to artery plaque, are turning up thousands of tiny thyroid tumors that otherwise might go undetected and often would do no harm.

"We call them 'incidentalomas,' " says Amy Chen, a head and neck surgeon at Emory University in Atlanta and American Cancer Society researcher.

But that's not the whole story. Two recent studies, including one co-written by Chen, show larger thyroid tumors are being found at an increasing rate, too. And those can't be explained by more aggressive diagnosis alone, researchers say.

"There is something else going on" to contribute to the 37,000 cases of thyroid cancer expected this year, Chen says. That's up from 18,000 in 2000.

What is that "something else"? In-depth research on that is just starting, says Elaine Ron, a senior investigator at the cancer institute. The good news, she says, is that 98% of those with the most common forms of the cancer live at least five years. Overall death rates are not rising. But it's important to study the rise in cases, she says: "This is a large increase, and it's been going on for a long time. If there's a biological reason, we can try to prevent it."

Among factors researchers are considering:

*Radiation: Researchers know radiation exposure, especially in childhood, can increase thyroid cancer risk. They don't know whether increased radiation exposure from medical scans and other sources is contributing to the overall increase.

*Obesity: Some early studies suggest it might be a factor -- and researchers know it's increasing.

*Diet: Some studies suggest diets low in fruits and vegetables or with iodine levels that are too high or too low might play roles.

Watching the research: Caroline Stetler of Washington, D.C. Stetler, 28, had thyroid cancer at 16. As a grad student at American University's Investigative Reporting Workshop, she researched the cancer and was shocked by the numbers.

"When I was diagnosed, the only question the doctor asked was, 'Were you ever exposed to head or neck radiation?' And the answer to that was no," she says. If environmental or lifestyle changes are contributing to the increase in thyroid cancer cases, "we have an obligation to find out," says Stetler, who contributed to a report on the mystery (investigativereportingworkshop.org).

Researchers also need to learn which small thyroid cancers could safely be left untreated, says Louise Davies, a researcher at the Department of Veterans Affairs Medical Center in White River Junction, Vt. She says there's no question some patients are undergoing unneeded biopsies, thyroid removal surgeries and radiation.

But which patients? Right now, doctors don't have good ways to tell. And they know even tiny tumors sometimes spread and cause serious problems, says Kenneth Burman, president of the American Thyroid Association and chief of endocrinology at Washington Hospital Center. The association says doctors may monitor some tumors less than 1 centimeter wide but should immediately treat anything bigger.

You may have thyroid cancer if...

Anyone with these possible signs or symptoms of thyroid cancer should see a doctor, says the American Cancer Society:

*A lump or swelling in the neck, sometimes growing rapidly.

*Pain in the front of the neck, sometimes going up to the ears.

*Hoarseness or other voice changes that do not go away.

*Trouble swallowing.

*Breathing problems (feeling like you are "breathing through a straw").

*A cough that continues and is not a cold.

(c) USA TODAY

New Agents in Thyroid Cancer Trials Suggest Treatment Paradigm Shift is "Not Far Off"

June 25, 2008 — Several new agents have shown activity in refractory thyroid cancer in phase 2 clinical trials. As the process of translating these research advances into therapeutic benefits for patients continues, it appears that a related paradigm shift in the treatment of this cancer is "not far off."

This is the conclusion of David Pfister, MD, and James Fagin, MD, from the Memorial Sloan-Kettering Cancer Center, in New York, writing in an editorial published online June 9 in the Journal of Clinical Oncology.

The editorial was prompted by 2 papers published online at the same time. They detail, separately, the results from phase 2 clinical trials with axitinib (under development by Pfizer) and sorafenib (Nexavar, Bayer and Onyx; marketed for use in kidney and liver cancer). Preliminary data from these studies have already been reported by Medscape Oncology. The editorialists draw attention to several other agents that have shown activity in phase 2 studies in thyroid cancer, but to date they are published only as abstracts (they were presented at the American Society of Clinical Oncology 43rd Annual Meeting in 2007). These include motesanib (under development by Amgen), vandetanib (under development by AstraZeneca), and gefitinib (Iressa, AstraZeneca and Teva; marketed for non-small-cell lung cancer).

Rush of Activity in Contrast to Limited Interest in the Past

This rush of activity is in contrast to past limited interest in developing therapeutics for thyroid malignancies, the editorialists comment. This limited interest can be partly explained by the natural history of the disease, they say. The vast majority (>90%) of thyroid malignancies are differentiated tumors, and standard treatment with surgery and thyroid-stimulating hormone (TSH) suppression often suffices. In many cases, ablation of the thyroid remnant with radioactive iodine 131 (RAI) is added to complete the treatment. This collective strategy has an overall survival rate of about 90% at 20 years, and the prognosis remains very favorable even among patients who relapse. Indeed, many patients with recurrent disease, even when incurable, will have an indolent course over months or years, with few or no symptoms and no treatment other than TSH suppression.

In this clinical setting, the efficacy of chemotherapy drugs has been disappointing. They benefit only a minority of patients, and might have significant toxicity, the editorialists write. In fact, there is only 1 drug — doxorubicin — approved so far for use in thyroid cancer by the US Food and Drug Administration.

However, the favorable prognosis for most patients with thyroid cancer should not lead to complacency, the editorialists comment. "Some patients do much less well," they write, and "better drugs are clearly needed to treat refractory thyroid cancers."

Axitinib and Sorafenib Reports Bring "Welcome News"

The reports on axitinib and sorafenib show that both drugs are active in a population of patients with thyroid cancer resistant or refractory to RAI.

Although no complete responses were reported, a significant minority of patients had a major response to therapy (30% on axitinib and 23% on sorafenib), according to Response Evaluation Criteria in Solid Tumors (RECIST). Also, it appears that most patients with stable disease had some disease regression, albeit of an insufficient magnitude to fulfill partial-response RECIST criteria. This suggests that the reports of stable disease "reflected at least in part therapeutic effect rather than simply slow growth of the disease," the editorialists write. Median progression-free survival rates were similar in both studies (about 18 months).

However, both drugs had adverse effects, and these were not mild. Axitinib was associated with grade 3 or worse adverse effects in 32% of patients, and 13% of patients discontinued because of toxicity. With sorafenib, 47% of patients required dose reductions and 20% discontinued because of toxicities.

Drug tolerability is particularly important in this patient population, the editorialists comment; many of these patients will be relatively asymptomatic and rapid disease progression is not imminent.

The reports on axitinib and sorafenib bring "welcome news," Drs. Pfister and Fagin write. This represents the first wave of such reports, they add, pointing out that the phase 2 trials currently available only as abstracts should be published soon.

However, the editorialists also emphasize the need for confirmation of these data. "Well-designed clinical trials will be critical to realizing these benefits in a timely way."

The preferred mechanism for this would be a randomized comparison of each agent to a standard approach, making the potential benefits of each drug clear. Taking into consideration the natural history of the disease and the fact that cytotoxics have shown minimal efficacy, the editorialists argue that phase 3 trials in patients with RAI-refractory differentiated thyroid carcinomas should have a placebo control (with early stopping rules) and should look at freedom from progression or progression-free survival rather than overall survival, given the potential for indolent disease behavior.

Dr. Pfister reports receiving research funding from AstraZeneca and Exelixis.

J Clin Oncol. Published online before print June 9, 2008.

American Society of Clinical Oncology 43rd Annual Meeting: Abstracts 6017, 6018, and 6020. Presented June 1–5, 2007.

TARGETED THERAPY FOR THYROID CANCER

August 10, 2009 (Toronto, Ontario) — Drug therapy has never figured largely in the treatment of thyroid cancer because traditional chemotherapy has little effect on the disease, but the new targeted therapies are making an impact. Several of these agents have shown activity in early clinical trials that has been hailed as "promising," and the accumulating data are generating considerable excitement among physicians treating these patients.

"These are the first drugs that have been shown to work and that have shown results," said Manisha Shah, MD, from Ohio State University Comprehensive Cancer Center in Columbus, who has headed one of these trials. "About 50% of patients benefit," she added.

At a session here at the World Congress on Thyroid Cancer 2009, Steven Sherman, MD, from the University of Texas MD Anderson Cancer Center in Houston, contrasted the situation now with the position 10 years ago, when there were no clinical trials at all in thyroid cancer. Even by 2005, no clinical trial in thyroid cancer had succeeded, mainly because of poor recruitment of patients.

The progress being seen now is because of close collaboration between endocrinologists and medical oncologists, a better understanding of the biology of the disease, and the emergence of the new targeted therapies, he told Medscape Oncology.

Sorafenib, sunitinib, axitinib, and motesanib have all shown activity in patients with differentiated thyroid cancer, as have vandetanib and XL184, which have shown activity in medullary thyroid cancer (MTC). There is also E7080, which is in clinical trials in both differentiated thyroid cancer and MTC, although no data have yet been reported with this agent, Dr. Sherman noted.

Many of these drugs are still under development, but sorafenib (Nexavar, Bayer/Onyx) and sunitinib (Sutent, Pfizer) are already marketed for use in several cancers, although not thyroid cancer.

All of these drugs are tyrosine kinase inhibitors, although they vary in their specific targets. However, a "common theme" is that they all inhibit the vascular endothelial growth-factor receptor, Dr. Sherman noted.

Although the data so far look promising, these drugs "are not curing patients," Dr. Sherman noted. There are no complete responses, he pointed out. They do seem to be effective in stabilizing patients with rapidly progressing cancer and they are prolonging progression-free survival, but whether this will translate into an increase in overall survival is unclear. For that, data from larger placebo-controlled trials are needed, he added.

Review of Results So Far

Dr. Shah reviewed the phase 2 data for differentiated thyroid cancer, summarized in the table below. She was involved in 1 of the 2 trials conducted with sorafenib, which is already on the market. Axitinib is under development by Pfizer and motesanib is being developed by Amgen.

Results from Phase 2 Trials

Results	Sorafenib, n = 58	Sorafenib, n = 30	Axitinib, n = 60	Motesanib, n = 93
Differentiated thyroid cancer (%)	93	90	75	95
Partial response (%)	15	23	30	14
Stable disease (%)	57	53	38	67
Median progression-free survival (months)	16	20	18	10

The results with axitinib and motesanib were highlighted as an advance in cancer research last year by the American Society of Clinical Oncology.

Dr. Shah cautioned against making direct comparisons because each trial had a slightly different patient population and different inclusion and exclusion criteria, but she told Medscape Oncology that the results seen in all of these trials were "in the same ball park."

At the same session, Dr. Sherman reviewed the data accumulating for MTC, which is much less common. Currently, the greatest interest is focused on XL184 and vandetanib, he told Medscape Oncology. Both of these drugs are now in phase 3 trials and the results are "eagerly awaited," he added.

A phase 2 trial with vandetanib (under development by AstraZeneca) showed a "slow and steady shrinkage of the tumor," with 33% of MTC patients achieving a partial response, and 63% achieving stable disease, Dr. Sherman noted.

Results for XL184 (under development by Exelixis) come from a phase 1 trial in which Dr. Sherman was involved; they were detailed at the meeting. The trial involved 85 patients, 34 of whom had MTC. A partial response was recorded in 14 of these 34 patients (41%), and the majority derived clinical benefit. This drug has gone straight from a phase 1 tril to a phase 3 international randomized trial, Dr. Sherman said.

Sorafenib has also shown activity in MTC. A phase 2 study of 19 patients reported earlier this year showed partial responses in 11% of patients and stable disease in 84%, he noted.

Sorafenib is now being tested in combination with tipifarnib in a phase 1 trial by Dr. Sherman's team. Tipifarnib was developed by Johnson & Johnson (as Zarnestra) for acute myeloid leukemia, but failed to get approval in 2005. It was added to sorafenib in this trial because it blocks pathways, important in MTC, that are not inhibited by the tyrosine kinase inhibitors, Dr. Sherman explained.

Results with the combination from the first 9 evaluable patients, presented at the meeting, show that "virtually every patient had some shrinkage of their tumor," he said. "When you compare the progression of the tumor in the year before treatment with that seen during treatment, you get a gut sense that these drugs are having a beneficial effect in this cancer," he added.

However, 1 of the phase 2 trials in MTC had disappointing results. The MTC portion of trial with motesanib failed to achieve its primary end point; partial response was seen in only 2% of the 91 enrolled patients. However, 81% of patients showed stable disease, which suggests that they were responding to the drug, just not enough to reach the partial-response level, Dr. Sherman noted. He added that pharmacokinetic analysis suggested the blood levels of the drug were low, and that higher doses might be needed.

Toxicity With Targeted Therapies

Both researchers highlighted the toxicities that can occur with the targeted therapies, and emphasized the need to monitor these patients closely. Dr. Sherman noted, in particular, concern over the fact that squamous cell carcinoma has been reported as an adverse event in patients receiving sorafenib, as well as some of the other agents.

In 1 series of patients with renal cell carcinoma, 5% developed squamous cell carcinoma and another 5% were found to have precancerous lesions, he said. The mechanism is unclear, but in patients showing this toxicity with sorafenib, the lesions appeared within 2 months of therapy initiation and receded when the patients were switched to sunitinib, he told meeting attendees. When asked whether it was only the skin that was affected, Dr. Sherman replied that it might not be — 1 patient also had a suspicious lesion in the lung — and he urged monitoring of all epithelial surfaces.

The toxicity of these targeted agents is a particular worry in thyroid cancer patients, because they could be taking these drugs for a long time, maybe years, he told Medscape Oncology. Patients who have been diagnosed with thyroid cancer live for many years — the specific-cause mortality rate with differentiated thyroid cancer is only 2%, and although the prognosis is worse for MTC, the 5-year survival rates are around 50% to 60%, other speakers noted.

"These drugs are not suitable for all patients with thyroid cancer," Dr. Sherman emphasized. They are not useful for patients with stable disease or those with slow-growing cancers, as this is the end result of the therapy, so "it's not worth the toxicity," he said. But they might make a difference in patients who have rapidly progressing disease, with cancer growing at a rate of 20% to 40% each year, he said.

The best place for these patients is in clinical trials, he continued. In fact, clinical trials are often the only option; most of the drugs of interest for thyroid cancer are still under development. Neither of the 2 already on the market is officially approved for use in thyroid cancer, although they could be used off label in such patients. In the United States, the National Comprehensive Cancer Network and the American Thyroid Association have both recommended that they can be used in the treatment of advanced disease, and because of this, such a use may be covered by medical-insurance organizations such as Medicare, Dr. Sherman noted.

As previously reported by Medscape Oncology, the results with targeted therapies in thyroid cancer have been welcomed enthusiastically, and have even led some experts to suggest that a paradigm shift in the treatment of thyroid cancer is not far off.

Dr. Sherman reports receiving research funding from Amgen, AstraZeneca, Eisai, Genzyme, the National Cancer Institute, and the V Foundation; receiving honoraria from Exelixis and Genzyme; serving as a consultant for Bayer, Exelixis, Eisai, Oxygen, Plexicor, Semaphore, and Eli Lily; and serving as a speaker for Genzyme. Dr. Shah reports receiving honoraria from Exelixis, Bayer, and Novartis.

World Congress on Thyroid Cancer (WCTC) 2009: Abstract 052, presented August 8, 2009; Abstract 0153, presented August 9, 2009.

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Patient Guide to Hand-Foot Syndrome | OncoLink Cancer Resources

Patient Guide to Hand-Foot Syndrome | OncoLink Cancer Resources

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Taking Steps to Cope With Chemo Brain

By JANE E. BRODY

Published: August 10, 2009

Cancer can be a life-changing experience, both physically and mentally. And when cancer treatment delivers a knockout punch to cognitive abilities, patients with the resulting “chemo brain” often face major challenges trying to get their lives back on track.

Do you have a question about the cognitive effects of cancer treatments? Dr. Silverman will be responding to readers this week.

But those who recognize the cognitive effects of toxic cancer drugs, adjust their schedules and learn to compensate for what are usually temporary limitations have an easier time returning to a productive life.

Barbara D. Wick of Chicago, for example, was working part time as an insurance consultant and serving on several not-for-profit boards while receiving chemotherapy for ovarian cancer. It was suddenly a challenge for her to deal with the complex problems presented by her professional and volunteer activities.

“I found it difficult to deal with more than one factor at a time and scary to have to think on my feet,” she said. “And I couldn’t trust my memory.”

She continued working but stopped taking new clients and transferred a difficult account to someone else. Helped by a support group, Mrs. Wick adopted new ways to handle professional and personal demands.

“I learned coping techniques that are not really different from those that would be used for people with memory loss,” she said in an interview. “I write everything down immediately, including appointments, doctors’ comments, ideas of things to do, plans and promises I’ve made. This gives me something to go back to, and using more than one modality — listening and writing — reinforces my ability to remember the information.”

She said she also became a “list addict.”“At night, I make a list of what I have to do and where I have to be the next day,” she said. “I’ve become religious about always putting things back in the same place — keys, cellphone, scissors, bills, everything. I pay bills on the same date and I double-check and proof everything, sometimes twice.”

Strategies for Staying on Track

The symptoms of chemo brain — commonly mental fogginess that can cause problems with memory, concentration, word retrieval, number processing, following instructions and multitasking — are widely known. And the effects, the causes of which are still unclear, are sometimes long-lasting.

In an excellent new book, “Your Brain After Chemo,” Dr. Daniel H. Silverman and Idelle Davidson quote a 52-year-old woman who was treated four years ago with drugs and radiation for breast cancer:

“Ever since I got lost in the shopping mall garage and couldn’t find my car, I always write down the level number and color code, etc., on the back of my parking ticket,” she told the authors. “And I always place parking tickets in the same section of my purse so I know where to find them. For extra measure, I’ll play a word game. If I’m parked on B1, for example, I’ll make up a cue like: Be one with the universe.”

Dr. Silverman, a leading researcher in the field, and Ms. Davidson, a health journalist and former cancer patient, offer a long list of suggestions to help people who are struggling with the cognitive effects of chemotherapy. Even though I don’t have chemo brain, several of their tips already help me keep track of a complex life despite an aging memory. And while I’m not yet ready to buy a personal digital assistant, I plan to adopt several other strategies.

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Prioritize. Because multitasking can be overwhelming to people with chemo brain, it helps to list tasks in order of their priority and concentrate on one at a time.

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Develop routines. Prepare the night before for the next day. Review your calendar, lay out clothes, pack your briefcase, perhaps even set up breakfast and prepare a brown-bag lunch. Take medications and exercise at the same time each day.

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Rehearse. On the way to a meeting where you will have to be on top of your game, visualize the room or the people who will be there and practice what you will say.

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Use word associations or rhymes. Maybe Harry has lots of hair and Mrs. Gold lots of money. Perhaps your daughter-in-law’s birth date is 2-4-68 or the combination on your gym lock is 2 (times) 6 (equals) 12.

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Rely on more than one sense. Try to link people and places with their scents, tastes, textures or unusual characteristics. Maybe Henry always wears a hat, or Rose’s front door is red.

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Use a notebook to record information. My surroundings are covered with sticky notes, and I search frantically for something I know I wrote down somewhere. The authors suggest a single notebook so that everything is in one place, and dating the pages as you use them. They say, “This frees your desk and your mind from clutter.”

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Post a checklist by the front door. Leave yourself a note of things to remember when you are going out — keys, wallet, walk the dog, close the windows, turn off the hose, check the faucets, lock the door.

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Write phone numbers on your phones. It doesn’t take chemo brain to forget a phone number, and I’ve noticed that many people don’t know their own cellphone number. Program as many contacts as you can into your cellphone, and keep a list of frequently dialed numbers next to your landline.

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Use a day planner. Write down all appointments immediately, with times, places and contact phone numbers. If you spend most of the day at a computer, you can use the calendar feature that alerts you to appointments. As a backup, I record things on a wall calendar and keep a paper tickle file, but this works well only if you check it regularly.

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Leave messages for yourself. If you have voice mail or an answering machine, you can use it to remind yourself of appointments or tasks you have to do. But again, this works only if you check it regularly.

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Timers can be lifesavers. I never put anything on the stove, in the oven or on the grill without setting a timer to warn me when to turn the heat down or off. I also have several 24-hour timers that I use as a wake-up alarm and to remind me when to move the car, pick up the grandchildren at school or put the laundry in the dryer.

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Get adequate rest. Even without chemo brain, fatigue is a memory destroyer. Don’t skimp on sleep, and when you feel your brain dragging, take a 20-minute nap. Stress impairs brain function, so practicing relaxation techniques like meditation and yoga can be very helpful as well.

Let Others Help

Finally, don’t bite off more than you can chew. Until and unless your brain recovers fully, simplify your life. Follow Mrs. Wick’s example if you can and reduce your workload or your hours. Perhaps even take a vacation or a leave of absence. Less work done well is better than a lot done poorly.

If those options seem like luxuries you cannot afford because you need to work, this is the time to rely on friends and family. Delegate chores. Say yes to people who offer to cook meals. Tell family members, especially, what coping tips you’re using so they don’t inadvertently derail your efforts. In as many ways as possible, give yourself a break.

This is the second of two columns on cognitive problems from chemotherapy. Last week: The symptoms of chemo brain.

The Fog That Follows Chemotherapy

By JANE E. BRODY

Published: August 3, 2009

As more people with cancer survive and try to return to their former lives, a side effect of chemotherapy is getting more and more attention. Its name is apt, if unappealing: chemo brain.

Nearly every chemotherapy patient experiences short-term problems with memory and concentration. But about 15 percent suffer prolonged effects of what is known medically as chemotherapy-induced cognitive impairment.

The symptoms are remarkably consistent: a mental fogginess that may include problems with memory, word retrieval, concentration, processing numbers, following instructions, multitasking and setting priorities.

In those affected — and doctors at this point have no way of predicting who might be — it is as if the cognitive portion of the brain were barely functioning. Symptoms are most apparent to high-functioning individuals used to juggling the demands of complex jobs or demanding home lives, or both.

The chemo brain phenomenon was described two years ago in The New York Times by Jane Gross, who noted that after years of medical denial, “there is now widespread acknowledgment that patients with cognitive symptoms are not imagining things.”

Some therapists have attributed the symptoms of chemo brain to anxiety, depression, stress, fatigue and fear rather than direct effects of chemotherapy on the brain and hormone balance. Yet when such factors dissipate, the symptoms may not. Recent studies that took other influences into account and analyzed how patients’ brains worked before and after cancer treatment have shown that cognitive effects of chemotherapy are real and, for some, long-lasting.

There are now two new books on the subject: “Chemobrain” (Prometheus Books), by Ellen Clegg, an editor at The Boston Globe, and “Your Brain After Chemo” (Da Capo Press), by Dr. Daniel H. Silverman, a leading researcher in the field, and Idelle Davidson, a health journalist and former breast cancer patient. Dr. Silverman heads the neuronuclear imaging section at the University of California, Los Angeles, Medical Center.

Ms. Clegg’s book, the more technical of the two, delves into details of research and may confuse readers about the validity of her subtitle, “How Cancer Therapies Can Affect Your Mind.” The more user-friendly book by Dr. Silverman and Ms. Davidson, subtitled “A Practical Guide to Lifting the Fog and Getting Back Your Focus,” acknowledges the controversy but cites both anecdotal and research reports showing that the problem exists independent of other factors that can beset cancer patients.

One Woman’s Symptoms

Barbara D. Wick, an insurance consultant in the Chicago suburbs who has been in and out of treatment for ovarian cancer for six years, says her cognitive problems have subsided somewhat since her last round of chemotherapy ended six months ago. Among the symptoms she experienced were these:

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Inability to focus on anything with any complexity or depth.

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Inability to retain information, especially names.

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Difficulty retrieving words and substituting wrong words (“chicken” for “kitchen”).

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Difficulty analyzing anything other than simple questions.

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Inability to follow instructions when cooking or knitting, for example.

In their book, Dr. Silverman and Ms. Davidson quote a photographer treated for breast cancer at age 34, who said: “Task completion is where I’m most affected cognitively. It’s as if the follow-through feature has been removed from my brain.”

Another patient, Patrick, a diagnostic radiologist treated for non-Hodgkin’s lymphoma at age 58, had to quit his job when he realized he was making mistakes. “I would lose my place and have to go back and start over with an exam,” he said. “I tried to explain a procedure to a patient and I got very confused.”

At the supermarket, Patrick and his wife put groceries in the car, then he drove off without her. He forgot pots on the stove until the smoke detector went off. Upset by the loss of his former self, he contemplated suicide. After psychiatric treatment, the depression lifted, but the confusion did not.

Searching for the Causes

It is not yet clear what happens during cancer treatment to cause symptoms of chemo brain. Some experts think some anticancer drugs could have direct toxic effects on neurons, although most drugs do not penetrate the blood-brain barrier. Some evidence from animal and human studies suggests that cancer treatment can cause biochemical or anatomical changes in the brain, or both.

Dr. Silverman reports that metabolic imaging studies have shown that “people exposed to chemotherapy have impaired brain function in certain regions compared to others who have not been exposed.”

Tim Ahles, director of neurocognitive research at Memorial Sloan-Kettering Cancer Center in New York, is looking into a possible relationship between chemotherapy-induced cognitive changes and DNA damage in breast cancer survivors.

Several symptoms of chemo brain resemble effects of estrogen loss after menopause caused by surgery. Since treatments for breast and ovarian cancers can suppress the production or action of estrogen, loss of estrogen may account in part for chemo brain in women.

Among women past menopause treated with an aromatase inhibitor that prevents the body from making estrogen or with tamoxifen, which blocks the action of estrogen on breast cancer cells, those on the aromatase inhibitor, which results in much lower levels of estrogen, “had significantly poorer performance on learning and memory measures,” Pauline M. Maki of the University of Illinois in Chicago reported.

Hormonal changes can also occur in men undergoing cancer therapy. In a study of men with prostate cancer treated with drugs that depleted androgens, treatment with an estrogen improved their performance on memory tests.

Controlling for brain function before cancer treatment begins can help determine cause and effect. In one study, cancer patients took a battery of neuropsychological tests before starting chemotherapy, three weeks after completing treatment, and again one year later. Although a third of the patients had signs of cognitive impairment before therapy began, the number jumped to 61 percent after treatment, and half remained impaired a year later.

This is the first of two columns on cognitive problems from chemotherapy. Next week: coping with the effects of chemo brain.

Hand-Foot Syndrome

• What is hand-foot syndrome?
• How do people describe hand-foot syndrome?
• What causes hand-foot syndrome?
• What can I do about hand-foot syndrome?
• How is hand-foot syndrome managed?
• What can family members and friends do to help me with my hand-foot syndrome?
• How can I talk to my family members and friends about my hand-foot syndrome?
• What should I report to my healthcare provider?
• What things should I discuss with my healthcare provider?
• Where can I get more information?
• References
• Supportive evidence-based practice

What is hand-foot syndrome?

Hand-foot syndrome is a condition caused by some types of chemotherapy where the palms of the hands and soles of the feet burn or tingle and then become red and sore. Sometimes the hands and feet become so painful that it may be difficult to hold objects in your hands, wear shoes, and even walk without discomfort. It is very important that all of these symptoms are reported to your doctor or nurse immediately. Early reporting of hand-foot syndrome is the best way to decrease the severity and prevent further complications.

How do people describe hand-foot syndrome?

Most of the time, the earliest symptoms of hand-foot syndrome are tingling and numbness with slight redness. Tingling and redness in the hands and/or feet can occur at any time while on chemotherapy. It can be expected with some drugs, too. Do not stop taking medication unless you receive other instructions from your doctor. Tell your healthcare provider know that you are experiencing these symptoms. If the redness continues, the hands and/or feet become red and swollen, or you have any discomfort contact your healthcare provider immediately.

Other more severe symptoms described are dryness, cracking, flaking, and small blisters or sores on the palms of the hands and/or soles of the feet. Hand-foot syndrome can be uncomfortable and interfere with your ability to do normal daily activities.

What causes hand-foot syndrome?

The exact cause of hand/foot syndrome is unknown. One theory is that the chemotherapy builds up in the sweat glands in the hands and feet. Heat or friction on the palms and soles increase the amount of the chemotherapy drug in the capillaries, which can leak out into the tissue. This leakage of drug results in the redness, tenderness, peeling, and discomfort in the hands and/or feet. The chemotherapy drugs most commonly reported to cause hand-foot syndrome include:

• Capecitabine (Xeloda®)
• Fluorouracil (5-FU) continuous infusion
• Liposomal doxorubicin (Doxil®)
• Idarubicin (Idamycin®)
• Floxuridine (fudr®)
• Continuous infusion of doxorubicin
• Sunitinib (Sutent®)
• Sorafenib (Nexavar®)

What can I do about hand-foot syndrome?

Prevention is very important in trying to reduce the development of hand-foot syndrome. Management involves modifying some of your normal activities to reduce friction and heat exposure to your hands and feet for a period of time following treatment. This period is about one week after receiving the IV medication and as long as possible while you are taking oral (by mouth) medications, such as Capcitabine or continuous infusion of 5-FU.

Here are some tips you might find helpful:

ACTIVITY

• Avoid long exposure of hands and feet to hot water. Examples of hot water exposures include washing dishes, long showers, or tub baths.
• Take short, cool water showers to reduce the drug exposure to the soles of your feet.
• Do not wear rubber gloves to wash dishes or clean. The rubber will hold heat against your palms.
• Avoid activities that cause unnecessary force or friction on the feet, such as jogging, aerobics, and long walks or standing for long periods of time.
• Avoid contact with harsh chemicals used in laundry detergents or household cleaning products.
• Avoid using garden tools, household tools (such as screwdrivers), and other tasks that require squeezing your hand on a hard surface.
• Do not use knives to chop food. It may cause excessive pressure and friction on your palms.
• Cool your hands and feet with ice packs or cool compresses for 15-20 minutes at a time. Do not apply ice directly to the skin.
• Elevate your hands and feet to avoid swelling when sitting or lying down.
• Pat skin carefully to dry. Try not to rub your skin with a towel.
• Apply mild skin care lotion to keep your hands and feet moist. Do not rub or massage lotion into your hands or feet. Rubbing or massaging can create friction.
• Avoid sunny windows, or sitting in the sun and wear sunscreen on all exposed skin when you go outside.
• Wear loose, well-ventilated shoes and clothes.
• Try gel inserts in your shoes.
• Wear cotton socks.
• Immerse hands and feet in cool water 3-4 times a day.
• Avoid wearing rings.
• Check your skin for signs of infections. Look for any drainage, odor, or increased redness. If you have an infection, you may also have a fever. If you notice any of these signs contact your healthcare provider.

COMMUNICATION

• Report any change in your daily activities to your healthcare provider.

DIET

• Drink 8 (8oz.) glasses of water or other non-caffeinated drinks every day. Avoid caffeine (i.e. colas, coffee) when possible. Caffeine can cause dehydration.

MEDICATION

• Over-the-counter drugs, such as Tylenol® or ibuprofen®, may be helpful to relieve discomfort associated with hand-food syndrome. Check with your doctor before taking any pain medication.
• Corticosteroids may be ordered from your doctor to help reduce swelling and redness.
• Taking Vitamin B6 (pyridoxine) may be beneficial in preventing and treating hand-foot syndrome and should be discussed with your doctor.
• Emollients such as Aveeno®, Lubriderm®, Udder Cream®, Bag Balm®, and Aquaphor® provide excellent moisturizing to our hands and feet.
• Avoid topical anesthetics or diphenhydramine-containing creams. These can make the toxicity of the skin worse.

How is hand-foot syndrome managed?

Severe cases of hand-foot syndrome are first treated by reducing or temporarily stopping the chemotherapy drug that is causing it. Other approaches that your healthcare provider may suggest include:

• Over-the-counter Tylenol® or ibuprofen® may help to relieve the discomfort associated with hand-foot syndrome. Check with your healthcare provider before taking any pain medication.
• Corticosteriods may be ordered by your healthcare provider to help reduce swelling and redness.
• Vitamin B6 (Pyridoxine) may be beneficial in preventing and treating hand-foot syndrome. Discuss this option with your healthcare provider before taking it.

What can family members and friends do to help me with my hand-foot syndrome?

Ask family members and friends to:

• Prepare meals for you.
• Help with daily household chores such as gardening or dishwashing.
• Test water temperatures before bathing or washing dishes. Inexpensive thermometers are sold in stores that can check water temperatures. This may be an option for you and your family.
• Help gently apply lotions to hands and feet.
• Help with your daily activities, such as bathing, and driving.

How can I talk to my family members and friends about my hand-foot syndrome?

Here are some ideas that may help you talk to family members and friends:

• Ask family members and friends how the hand-foot syndrome is affecting them.
• Talk to family and friends how the hand-foot syndrome is affecting your emotions and mood.
• Talk to family and friends how the hand-foot syndrome is interfering with your life and ability to function.
• Ask family members for suggestions to help you function as close to normal as possible.

What should I report to my healthcare provider?

If you experience any of the following symptoms, report them to your healthcare provider:

• Redness, swelling, tingling, or pain in the hands and/or feet. Discuss any symptoms with your healthcare provider immediately. Do not stop your medication until you have talked to your healthcare provider.
• Any temperature rise above 100.9 F (38.3 C), or a temperature higher than 100.4 F (38.0 C) that lasts for more than an hour, or as set by your doctor's office.
• An increase of 4 stools over normal bowel pattern in a 24 hour period or diarrhea during the night.
• Tenderness, redness, or sores in the mouth.
• Vomiting.
• Unable to keep down any fluids for 24 hours.

What things should I discuss with my healthcare provider?

If you are experiencing hand and foot syndrome, you should discuss the following with your healthcare provider at your next appointment:

• Will my chemotherapy put me at risk for developing hand-foot syndrome?
• Are there things you can give me if my hands and/or feet become painful?
• Will I be able to continue to work?
• If I do all of the things suggested could hand-foot syndrome be prevented?
• What symptoms do you want me to call you for?

Where can I get more information?

For more information, contact the people or organizations at the numbers or websites listed below:

• Contact your healthcare provider.
• Caring 4 Cancer: http://cancer.caring4health.com/default.aspx Click on managing side effects (in the center of the page), then click on less common side effects (In the right hand column), and finally on hand-foot syndrome (located in the right hand column).
• Chemocare: http://chemocare.com Click on managing side effects and then hand-foot syndrome.
• American Cancer Society: 1-800-ACS-2345 or http://www.cancer.org
• Family Care Research Program: http://cancercare.msu.edu/
• National Cancer Institute: 1-800-4-CANCER or http://www.cancer.gov/cancerinfo Click on coping with cancer.

References

• Backes, W. ( 2001). Prodrugs. Clinical Journal Of Oncology Nursing, 5(1), 35-37.
• Oestreicher, P. (2007). Manage Skin Toxicities Associated with Targeted Therapies. ONS connect, 22(11),20-21.
• R4 Healthcare LLC. (2008). Caring4 Cancer: Your complete source for knowledge & support. Retrieved from http://cancer.caring4health.com/default.aspx
• The Cleveland Clinic Foundation (2005). Chemocare.com. Retrieved from http://chemocare.com
• Wood, L., S. (2006). Managing the side effects of Sorafenib and Sunitinib. Journal Of Community Oncology, (3)9, 558-562.

Supportive evidence-based practice

• Coyle, C., & Wenhold, V. (2001). Painful blistered hands and feet. Clinical Journal Of Oncology Nursing, 5(5), 230-232.
• Gressett, S. Stanford, B., & Hardwicke, F. (2006). Management of hand-foot syndrome induced by Capecitabine. Journal Of Oncology Pharmacy Practice, 12(3), 131-141.
• Pike, K. (2001). Hand-Foot Syndrome. The Oncology Nursing Forum, 28 (10), 1519-1520.
• Wilkes, G., & Doyle, D. (2005). Palmar-Planter Erythrodysesthesia. Clinical Journal Of Oncology Nursing, 9(1), 103-106.

How cancer drugs cause hypertension: why aren't scientists researching more nutrition solutions?

ugust 10, 12:20 PMSacramento Nutrition ExaminerAnne Hart

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Scientists are learning more about how cancer drugs cause hypertension. According to an August 5, 2009 article in Healthday News, “Scientists Learn How Cancer Drugs Cause Hypertension,” A new study reveals why high blood pressure develops in up to one-third of cancer patients who take drugs to block the formation of blood vessels that feed tumors.”

Could this research point to more of a nutritional approach to controlling hypertension when the cause is not an adrenal tumor, Cushing’s disease, too much water retention, or too high angiotensin-renin levels from a kidney gene variant, extreme salt sensitivity, a combination of numerous drugs with interactions, or other known causes of the high blood pressure?

According to the article and study,"Anti-angiogenesis drugs like Avastin, Sutent or Nexavar inhibit an important substance called vascular endothelial growth factor [VEGF] that stimulates the creation of new vessels that support malignant growth," senior study author Dr. Thomas Coffman, a professor of medicine, cell biology and immunology at Duke University Medical Center in Durham, N.C., said in a school news release. "Our studies in mice show that blocking VEGF causes hypertension because it disrupts an important biological system -- the nitric oxide pathway that regulates blood vessel health."

The study noted how the researchers used an antibody to block an important VEGF receptor called VEGFR2. After about a week, the mice that received a high dose of the antibody showed a "rapid and sustained" increase in blood pressure.

Dr. Coffman reported to Healthday News in the article that "The higher doses of anti-angiogenesis drugs that patients need to keep their cancers from growing translate into a significant increase in risk for hypertension and, by extension, for cardiovascular complications." You can read the study online in the journal, Hypertension. The study appeared online on August 3, 2009.

Interestingly, few articles are appearing suggesting a vegan diet and lifestyle changes for treating hypertension in cancer patients. Instead, numerous sources are saying it’s because cancer patients are living longer, side effects are popping up and have to be paid attention to. Could the cause have anything to do with the nutrition? Or is it the drugs?

What usually happens is that doctors control the hypertension in cancer patients with traditional blood pressure medications. So now the cancer patient takes not only the cancer drugs that may be causing the hypertension in the first place, but also has to take drugs to control high blood pressure.

Not many doctors are giving patients ADMA tests to see whether due to a gene variant, their bodies aren’t making enough argenine which in turn makes nitric oxide that relaxes the blood vessels and lowers the hypertension. Will argenine and citrulline help those patients? Maybe, but not if they've recently had a heart attack.

There are studies reporting sudden deaths after heart attack from patients taking argenine in a clinical trial. On the other hand, no one yet has researched whether the argenine did them in or was it other causes--just that they had been given the supplement after having recuperated from a recent heart attack. So the research remains open as to how other approaches work or not work.

With all these drugs for cancer patients plus more drugs to control the high blood pressure possibly caused by the cancer treatments and other drugs, why isn’t anyone proposing a nutrition-based solution to the high blood pressure once the cancer is in remission? For further information, see the publications at the U.S. National Heart, Lung, and Blood Institute has more about hypertension. Also see: US News.com resource sites such as: cancer, drugs.

From a nutrition point of view, only the naturopaths are taking into consideration that when a cancer patient is given drugs for cancer on top of drugs for high blood pressure, the pill combinations need to be studied as to how all those drugs interact with the person's body.

There are few press releases in mainstream media about nutritional approaches. And patients are reluctant to look at media that is pre-judged as illogical if it is different from the usual traditional medical approaches, even if nontraditional media only contains lists of medical articles published in validated, credible, and reliable medical journals. For the patient, the question is, who is funding the research on nutritional approaches to finding the root causes of various diseases? And how far can food as medicine go to prove it's not a placebo effect?

Interestingly, research also shows that certain blood types are resistant to specific cancers. For example, type O blood is resistant to pancreatic cancer, which is found mainly in A, B, and AB blood type groups. See the article, "ABO Bood Group and the Risk of Pancreatic Cancer," JNCI, Journal of the National Cancer Institute, published online, March 2009.

The question for researches is, if one doesn't have blood type O, is nutrition the best way to protect against pancreatic cancer in blood types not resistant to pancreatic cancer? And if so, what foods and/or supplements are best for blood type A, B, and AB to resist any type of cancer, if they are more at 'risk' based on blood type? The goal is to take as few drugs as possible and find the root causes of disease by treating the whole system with nutrition tailored to an individual's specific metabolic and genetic requirements.

Hand-Foot Syndrome Preventing and Managing Hand-Foot Syndrome

By Lisa Fayed, About.com

Updated: July 08, 2009

About.com Health's Disease and Condition content is reviewed by our Medical Review Board

See More About:

• chemotherapy side effects
• capecitabine
• dry skin

Hand-foot syndrome (HFS) (palmar plantar erythrodysesthesia) is a dermatological side effect of some chemotherapy and biological therapy medications. It primarily affects the palms of the hands and soles of the feet. HFS occurs when small amounts of medication leak outside of the capillaries and cause damage to exposed tissue. Most people who have HFS develop mild effects, but some can suffer severe effects, making daily living activities nearly impossible.

Hand-foot syndrome is most commonly associated with the drug Xeloda (capecitabine)*. Other drugs that are known to cause hand-foot syndrome include:

• 5-FU (fluorouracil)*
  
• Cytosar-U (cytarabine)
  
• Adriamycin (doxorubicin) - continuous infusion
  
• FUDR (floxuridine)
  
• Doxil (liposomal doxorubicin)
  
• Idamycin (idarubicin)
  
• Nexavar (Sorafenib)
  
• Sutent (Sunitinib)

Keep in mind that not all people who take these cancer drugs will develop hand-foot syndrome.

_{*Dihydropyrimidine dehydrogenase (DPD) deficiency -- having a different set of metabolic enzymes than normal -- is the usual culprit for very serious and immediate HFS that occurs with use of these drugs. It is usually accompanied by severe diarrhea. About 5% of Americans have this deficiency. Testing for it is not routine, but your doctor may do so if you need to take one of these drugs.}

Symptoms of Hand-Foot Syndrome

Common symptoms that accompany hand-foot syndrome include:

• tingling or numbness
• burning
• redness
• swelling
• tenderness

In severe cases of hand-foot syndrome, the skin may begin to blister or develop sores or ulcers. Dry, flaky skin that may or may not peel can also occur. This can greatly affect someone's quality of life, especially his ability to walk and use his hands. In clinical trials, about 5% to 10% percent of people experienced these complicated effects of hand-foot syndrome.

Fingerprint loss has been associated with the use of the cancer drugs that cause hand-foot syndrome. This rare side effect is thought to be related to the length of time in which the drug is taken. The peeling and blistering of the skin over time may cause the fingerprints to be erased. Hand-foot syndrome gained much media attention in 2009 when a Singapore man was detained at U.S. Customs for not having fingerprints. His condition was related to taking capecitabine for three years.

Preventing and Managing Hand-Foot Syndrome

Prevention is key with HFS. Heat and friction are two factors that worsen capillary leakage. For a week after being given IV medication, or for the entire period you are taking oral cancer drugs, there are several precautions you can take to help prevent and manage HFS:

Avoid Hot Water -- Exposing skin to hot water for long periods (taking tub baths and showers, for example), dishwashing, and relaxing in a hot tub are not recommended. Taking a tepid or short cool shower is best for a week after taking IV meds or through the timeframe that you are taking oral medication. Rubber gloves do not offer protection -- they actually heat up the hands. Your doctor may also recommend that you specifically do not take a hot shower or bath 24 hours prior to treatment.

Avoid Exercise and Manual Labor -- Exercise that puts a lot of pressure and stress on the hands and feet, such as aerobics, long walking, jogging, and weightlifting (even with gloves), should also be avoided. Manual labor like gardening and yard work should also be avoided.

Wear Loose Fitting Clothing -- Tight fitting clothes and shoes can cause friction, thus leading to increased capillary leakage. Wear comfortable shoes with cushioned soles. Do not walk in bare feet; cotton socks or soft slippers are best.

Do Not Wear Rings -- To limit friction, avoid wearing rings on your fingers. Rings that are never removed, like wedding rings, can be a source of bacteria as well. Bacteria can become trapped in between the ring and the finger. Infection prevention and control is very important with HFS due to the sensitivity of the skin.

Keep Hands and Feet Cool -- Throughout the day, apply ice packs or cool compresses to hands and feet. Immersing them in water a few times a day is also helpful.

Apply Emollients -- Emollients are specialized moisturizers that soothe dry, cracked, and irritated skin. Most doctors recommend emollient products such as Aveeno with lanolin, Lubriderm, Udder Cream, Bag Balm, and Aquaphor. You can apply emollients several times a day, but be sure not to rub the skin with much pressure. Wearing socks and gloves after application will help to hold moisture.

Stay Well Hydrated -- Dehydration is also a cause of dry skin, so it is important to keep well hydrated by drinks lots of water. Caffeine is a known cause of dehydration and should be avoided.

How Your Doctor May Manage Hand-Foot Syndrome

Mild cases of HFS may not require medical intervention, just careful monitoring by you and your nurse and doctor. If you begin to notice any symptoms of HFS, call your oncology nurse or doctor. If you suffer from HFS and notice it worsening, it is very important to call your doctor right away.

Moderate to severe cases of hand-foot syndrome that interferes with daily living activities is considered to be a serious complication of treatment and is treated as such. Halting treatment or lowering the dosage may be necessary. OTC pain medications like ibuprofen may be recommended to relieve the pain. Oral or topical corticosteroids may help some with inflammation.

High doses of vitamin B6 are often recommended for people who are likely to develop HFS or already suffer from it. Oncologists often recommend short term use of 50 to 150 mg of B6, which is considerably higher than the daily recommendation. Always consult your doctor before taking B6 for HFS.

Many studies are being conducted about the prevention and management of hand-foot syndrome. The role of nicotine patches, henna, and vitamin E are among many things that being studied for the relief of HFS.

_Sources:

_{Gressett et al. Management of hand-foot syndrome induced by capecitabine. J Oncol Pharm Pract.2006; 12: 131-141}

_{K. Gelmon, A. Chan, and N. Harbeck The Role of Capecitabine in First-Line Treatment for Patients with Metastatic Breast Cancer Oncologist, September 1, 2006; 11: 42 - 51.}

Suggested Reading

Friend with Hand-Foot Syndrome - How to Help a Friend with Hand-Foot SyndromeCapecitabine and Fingerprints - Will I Lose My Fingerprints to CapecitabineArm and Hand Remedies

Single-Agent TKIs Effective in Treating Thyroid Cancers That Respond Poorly to Other Treatments: Presented at WCTC

By Cameron Johnston

TORONTO -- August 10, 2009 -- Both sunitinib and sorafenib, used as single agents, appear to be useful for treating differentiated thyroid cancer that has failed to respond to radioactive iodine therapy, according to a study presented here on August 9 at the annual World Congress on Thyroid Cancer (WCTC).

According to Maria Cabanillas MD, University of Texas M. D. Anderson Cancer Center, Houston, Texas, 1 in 5 patients with differentiated thyroid cancer will develop distant metastasis, and of those, 50% will not respond well to iodine therapy.

Therefore, the advent of tyrosine kinase inhibitors (TKIs) has been a welcome addition to the list of possible treatments clinicians can offer those patients. However, she added, to date, TKIs have only been used in multiple-drug regimens. This study is believed to represent the first time they have been used as single agents to treat the disease.

The study enrolled 33 patients, but 18 were disqualified because they had received multiple drug therapies, or for other reasons. In the present analysis, 13 patients received sorafenib, and 2 received sunitinib. Both patients receiving sunitinib had tried, and failed treatment with sorafenib.

The patient's median age was 61 years and median time on therapy was a 49 weeks (range, 13-81 weeks).

The data showed that 3 out of 15 patients (20%) had a partial response to TKI therapy, 9 (60%) had stable disease, and 3 (20%) had tumours that continued to progress even after treatment. This represents a clinical benefit rate of 80%, Dr. Cabanillas said, with a durable response rate seen in 10 of the 15 (66%).

Dr. Cabanillas pointed out that the improvements seen in the patients' lungs were more robust than the responses seen in the lymph nodes. Lung metastasis showed a median regression of 16%, compared with a progression of 3% in the patients' lymph nodes.

The single-agent drugs also produced significant improvements in progression-free survival (19 for TKI compared with 4 months when they were not on TKI; P = .001). Dr. Cabanillas said the median overall survival had not yet been reached, but in these patients would be greater than 24 months.

The response to TKI therapy was similar in patients regardless of the tumour histology. Furthermore, 6 of 8 patients with papillary carcinoma underwent genetic testing for BRAF mutation and 3 of these patients were also confirmed positive for another mutation, V600E, also associated with a more aggressive disease.

Although single-agent TKIs proved beneficial in this small group of patients, Dr. Cabanillas cautioned that these patients had differentiated cancers which are easier to treat than medullary or anaplastic cancers. As a result, it is not possible to generalise these findings to patients with other sub-types of thyroid cancer.

[Presentation title: Treatment With Tyrosine Kinase Inhibitors (TKIs) for Patients With Differentiated Thyroid Cancer (DTC): The MD Anderson Cancer Center Experience. Abstract P29]

Sunitinib Offers Favourable Outcomes for Patients With Refractory Thyroid Cancers: Presented at WCTC

By Cameron Johnston

TORONTO -- August 11, 2009 -- Patients with thyroid cancers who are refractory to radioactive iodine therapy, and/or have progressed following surgical resection of the thyroid seem to show favourable responses when treated with sunitinib, according to a study presented here at the World Congress on Thyroid Cancer (WCTC).

Ezra Cohen, MD, University of Chicago, Chicago, Illinois, presented the preliminary results of a phase 2 study at an oral presentation on August 8.

The study results included only patients with differentiated cancers; the results from a second cohort of patients with medullary carcinomas were not presented.

Patients in the study had either papillary (n = 18), follicular (n = 8), Hurthle cell (n = 10), or insular (n = 2) thyroid cancer.

Of the 38 who were enrolled, 37 had been treated with radioactive iodine, 35 had had prior surgery, 15 had had external beam radiation therapy (EBRT), and 6 had had systemic chemotherapy. Many had a combination of therapies.

All patients had shown signs of progressive disease within the previous 6 months before being enrolled in the study. Thirty-one patients had distant metastases at the time of enrolment.

Patients were treated with sunitinib 50 mg/day on a 4-week-on/2-week-off cycle.

Overall, 26 patients (68%) had stable disease and 7 (18%) had a partial response. Progression-free survival was 57% and 34% at 1 and 2 years respectively. Overall survival was 76% and 70% at 1 and 2 years respectively.

Treatment response was determined according to modified Response Evaluation Criteria in Solid Tumors (RECIST) criteria as well as by the patient's decrease in thyroglobulin levels.

Adverse events were very common in this study group, although according to Dr. Cohen, they were not unexpected and were comparable to what had been seen in other studies when sunitinib was used to treat renal cell carcinoma.

A total of 5 patients discontinued the study due to adverse events, which included fatigue (79%), diarrhoea (56%), and hand-foot syndrome (53%). There were also 3 toxic deaths, which were felt to be related to the sunitinib (1 case of sepsis, 1 of liver failure, and 1 of left ventricular failure).

Half of the patients (19/38) had to undergo dose reductions as a result of the aggressive toxicity profile.

Nonetheless, Dr. Cohen said sunitinib is an active agent, showing an 87% response rate among patients whose thyroid carcinomas were refractory to virtually all other available treatments.

[Presentation title: Sunitinib in Patients With Radioactive Iodine Refractory and Progressive Differentiated Thyroid Cancer: A Phase 2 Study. Abstract O51]