Sunday, June 13, 2010

Vitamin D with Calcium Reduces Cancer Risk in Women

John A Milner, PhD, Chief of the Nutritional Science Research Group, Division of Cancer Prevention at the National Cancer Institute presented a talk on vitamin D supplementation at the recent meeting of the American Society of Clinical Oncology (ASCO) in Chicago. He stated that current guidelines suggest 400 IU of vitamin D, possibly more for the elderly, up to 600. He also noted that too much vitamin D can be toxic, e.g. 50,000 IU daily for a long time, but that there is probably a safe range between those.

He cited the 2007 data from a Creighton University four-year study of 1179 healthy women aged 59-73, all from rural Nebraska. Subjects took 1400-1500 mg calcium and 1100 IU vitamin D daily, and the study was designed to assess the effect on bone health. In a secondary analysis of the results, researchers found that subjects taking the supplements had almost a 75% reduction in the risk of cancer, all cancers.

Dr Milner noted that the study did not have a "vitamin D only" arm, so there was no way to assess the value of taking vitamin D supplements alone. The NIH is funding further research. Further, he cautioned that other studies have shown that too much vitamin D actually increases the risk of some specific cancers. He also believes that this is a very individual issue, and that additional research will help doctors understand just who might benefit from supplementation and who might not.

I have been taking 1200 mg calcium and 2000 - 5000 IU vitamin D3 (cholecalciferol) daily for several years now. I don't plan to change, but I may have my vitamin D level measured and then see. From his talk, it appeared that the risk of breast cancer and other diseases started to increase as the blood serum concentation of vitamin D reached 60 to 100 nanomoles/L (24 to 40 ng/mL).

This may be the last ASCO post. I'm out of subjects. Back to regular stuff.

Dinner aboard the Amtrak Empire Builder, Chicago to the Twin Cities, slightly blurred by the motion of the train:
Dinner aboard the Amtrak Empire Builder

ASCO Presentation: Selenium and Vitamin E Do Not Prevent Prostate Cancer

The government-funded Selenium and Vitamin E Cancer Prevention Trial (SELECT) included 36,000 men, each having a PSA of 4 or less, at many different medical centers, for 5.5 years, and cost $100 million dollars. The men took selenized yeast and vitamin E, or a placebo. Eight percent were smokers. Now seven years later, there is no evidence of a reduced risk of ANY cancer, especially prostate cancer, which the researchers expected would be reduced.

Other studies had suggested a benefit, and researchers don't know why it didn't appear. The presenter, Eric Klein MD, suggested that we may need to take a more comprehensive approach, evaluating the benefit of whole foods instead of discrete nutrients. He pointed to a rat study showing a benefit from tomato powder where there was no benefit from lycopene, the studied nutrient. Maybe a single nutrient only helps people who have a deficiency in that nutrient.

He closed by suggesting that such disappointing results might make it difficult to get another $100 million for the next study!

That's quiche in the middle. Sort of. Good stuff.

Monday, June 7, 2010

Three More Drugs at ASCO

Several speakers at the ASCO conference mentioned carfilzomib and pomalidomide as the most-promising new drugs in our futures. I posted about those here. At least three other new drugs also show promise: (1) Elotuzumab, (2) Denosumab, and (3) Vorinostat.
  • Elotuzumab is a laboratory-manufactured monoclonal antibody which works against a cell surface glycoprotein, CS1, highly expressed in multiple myeloma (MM). Like the antibodies that our own bodies produce, it attaches to the target protein and kills or disables the cell possessing that protein. It has been tested successfully in Phase I and II trials with both Velcade and Revlimid. In the Revlimid trial, 28 patients with lots of prior therapies experienced an overall response rate of 82%. Not bad. I personally believe that many more monoclonal antibodies are in our future - these are the "silver bullets," highly-directed therapy that really could make myeloma a chronic disease. Someday, not yet.

    By the way - the suffix "mab" on the generic drug name elotuzumab means "Monoclonal AntiBody." We'll see more MABs.

  • Denosumab (see - here's another) is also a monoclonal antibody, this time directed at a signal protein which promotes bone removal. Thus denosumab inhibits destruction of bones by myeloma and its treatments. This is cool stuff. Several Phase III studies were reported at ASCO, all of them showing an advantage for denosumab over Zometa. Quoting the conclusion of one study (9042), which included myeloma patients: "In this head-to-head study, patients receiving denosumab had longer time to first skeletal-related event (SRE) or hypercalcemia and time to radiation to bone compared with Zometa. A lower proportion of patients experienced an on-study SRE in the denosumab group compared with Zometa." In another study, patients taking denosumab experienced less bone pain than those taking Zometa.

  • Vorinostat, brand name Zolinza, is already approved for some cancers. It is a new class of drug called histone deacetylase (HDAC) inhibitors. I don't know what means, actually, except that it works by a different mechanism than Revlimid, Velcade, melphalan, or dexamethasone, making it an excellent candidate for use WITH those drugs. So far it looks promising in early studies with both Velcade and Revlimid. Another HDAC inhibitor, panobinostat, also shows promise.

Nice salmon dinner aboard the Amtrak Empire Builder:

Maintenance or Not - A Patient Perspective

I posted about this three days ago, but have now heard the talks and thought about it some more.

At least three different papers at the American Society of Clinical Oncology (ASCO) make this clear: When a good response (from a transplant or drug combo) is followed by continuous maintenance with a single agent drug, the time of remission may be extended significantly.

For example, I get an autologous stem cell transplant (SCT), or I go on a multi-drug treatment, and achieve a "very good partial response" (VGPR) or even a "complete response" (CR). That may be followed by a couple of months of additional drug therapy, such as Velcade or Revlimid with dexamethasone (Dex), to "consolidate" my response and hopefully improve it even more. Then I would LOVE to go on a drug holiday for a while, but instead I start taking Revlimid at 10 mg/day, 21 days out of each 28 (example). According to one study, my chance of remaining free of disease progression for three years would be increased from 35% to 68% because I took the maintenance drug.

Speakers at the conference used words like "new treatment paradigm," implying that post-SCT maintenance will soon be the standard of care. Mostly they mean maintenance with low-dose Revlimid as a single agent.

Having thought it over, though, it may not be a simple choice for me. For instance, we know that the myeloma will eventually return in either case, so if I take Revlimid for maintenance, will I still have it available as a possible therapy later when the disease does come back? My very knowledgable friend says maybe so, because (1) the Revlimid dosage will be higher; (2) and it can be combined with other agents such as Dex and even melphalan or Velcade. I am skeptical, but neither of us is a doctor, and this question really did not come up at the talks. I sure do want to get the opinion of my Dr L.

Here are some pros and cons from my point of view.

Pro Maintenance
  • A longer time before my tumor burden goes up and my doctor and I have to figure out a new plan. Just take the drug and don't think too much about it.
  • More-frequent blood tests. These will be necessary to check for drug side effects, and in my view this is a pro rather than a con because the tests may reveal other problems, including disease progression, sooner than otherwise.
  • A greater chance that a brand-new therapy will be available by the time I need it. How cool would that be!
  • Maybe, but not for certain, a longer life. See below.
Pro Drug Holiday
  • Regular, ordinary, high-quality life, including:
    • Freedom from the suffocating expense of Revlimid or whatever is my maintenance drug. This affects some people much more than others.
    • Freedom from the side effects. So does this.
  • When the myeloma does come back, Revlimid may be fully available as my next therapy. It might be anyway, but I suppose more likely if the myeloma hasn't come back in the face of Revlimid maintenance.
The studies aren't mature enough yet to show an actual survival advantage for maintenance. It is possible that they will never show one because the myeloma will eventually return in either case, at which point other therapies will be tried, and some may succeed.

I am not actually facing this decision right now, and I invite you to comment if you are. Aw heck, comment anyway. :-)

Below: A slide by the lead researcher in the study of the drug that I am currently taking. I'm still receiving primary therapy, not maintenance. Pomalidomide is good stuff

By the way, Blogger was down for a day and just came up, so look farther down for posts that got stacked up in the interim.

Estrogen in Chicken and Beef

Japanese researchers presented a poster titled "Does dietary estrogen intake from meat relate to the incidence of hormone-dependent cancers? (1553)" Unfortunately, they did not answer their own question. They did measure estrogen levels in checken and beef from three countries, however, finding high levels of estrogen in USA chicken and beef. They summarized the work as follows, quoting directly from their abstract:

"The high estrogen concentrations in Japanese chicken, USA chicken, and USA beef have been attributed to the residue of external estrogen in the feed given to the livestock. The nearly zero level found in Japanese beef and Brazilian chicken is considered to be natural endogenous amount without estrogen supplementation. The estrogen levels in meat are much lower than those of contraceptive pills (0.035 mg/tab). Even so, when considering lifetime exposure to meat containing higher level of estrogen than human fat tissue, estrogen intake from daily meat consumption cannot be disregarded as a factor governing human health. Consequently, dietary estrogen intake from meat might promote estrogen accumulation in the human body and could be related to the incidence of hormone-dependent cancers."

Hmmm. The researchers did not say how they obtained the USA chicken and beef, but I suspect that it was not from organic sources. I do believe in buying only organic meat, or at least meat that is advertised "no added hormones." It may cost more, but cancer is a real bummer.

Some of the 30,000 people at ASCO: McCormick Center in Chicago

Complementary Treatments and Therapies

I believe that we can improve on the treatments offered by conventional medicine. In particular, I believe a healthy lifestyle with the best possible food, plenty of aerobic and resistance exercise, good sleep, and freedom from excessive stress. Beyond that are naturopathic therapies and supplements which might help against the cancer, or especially against the side effects of the cancer or the drugs.

Several papers at this year's ASCO meeting dealt with such complementary therapies, which apparently can improve both the cancer outcome and the patient's quality of life. These are scienfific studies by serious researchers at well-known medical centers, with the papers approved by ASCO's review committee. One of those, a study at MD Anderson, determined that as many as 54% of patients use complementary or alternative medicine in some form. (9091). None of studies below are specific for myeloma patients, but they might to be applicable to anyone in cancer treatment:
  • Neuropathy:
    • A study of topical menthol for treatment of peripheral neuropathy concluded that two thirds of patients with long-term neuropathy experienced an improvement in pain and function. (9129). I'm thinking it would smell good too.
    • Another study, of electrostimulation with a machine called the MC5-A Calmare therapy device, seemed to show that it "appears to dramatically reduce pain in refractory CIPN (neuropathy) patients with no toxicity." (9029). For a few patients, pain was reduced to zero after ten daily treatments. Normally I would be skeptical of such a study with a specific machine, wondering about the objectivity of the authors. They do not report any conflicts, though, so maybe it's worth a try. But I wouldn't buy the machine - better to find a therapist who already has one.
    • There is no rule saying that a person in pain can't try both of these, along with the other naturopathic remedies that are out there.

  • Fatigue:
    • Guarana is a plant native to the Amazon basin that has been used as a stimulant since pre-Columbian times. Patients in a Brazilian cancer center were given 50 mg of guarana extract twice daily, and the researchers reported "Guarana is an effective, cheap and nontoxic alternative for the treatment of fatigue in breast cancer patients receiving systemic chemotherapy." (9007).
    • Rochester researchers studied 410 survivors of many different cancers and found that "YOCAS yoga intervention significantly improves sleep quality, fatigue, and quality of life while reducing sleep medication use among survivors." (9013).
    • The Bangalore Institute of Oncology studied 66 metastatic breast cancer survivors and concluded "The results offer preliminary support for stress reduction benefits of yoga intervention. However larger randomized controlled trials are needed to validate these findings." This study even found that yoga increased the number of NK (natural killer) cells, suggesting a possible clinical benefit beyond just quality of life. (9099).

  • Actual Therapy (this is probably not "complementary" but an interesting use of an inexpensive natural substance): Mistletoe extract. A consortium of cancer centers studied 44 patients with a variety of advanced solid tumors (breast, prostate, ...) using a combination of mistletoe extract (EMEX) with a drug called gemcitabine (GEM), concluding "The EMEX/GEM combination demonstrated limited toxicity, no alterations of GEM Cp during infusion of EMEX, clinical benefit in 48% of patients, good tolerability and excellent EMEX compliance. Addition of EMEX may allow for use of higher doses of GEM and increase the (minimum neutrophil count)." (2559). Note that the work was done with solid tumors and may have no application to myeloma.

(2559) NCCAM/NCI phase I study of mistletoe extract and gemcitabine in patients with advanced solid tumors.
(9007) Effect of guarana (Paullinia cupana) on fatigue in breast cancer patients undergoing systemic chemotherapy.
(9013) Effect of YOCAS yoga on sleep, fatigue, and quality of life: A URCC CCOP randomized, controlled clinical trial among 410 cancer survivors.
(9029) Pilot trial of a patient-specific cutaneous electrostimulation device (MC5-A Calmare) for chemotherapy-induced peripheral neuropathy.
(9091) The use of complementary and alternative medicine in patients seen in phase I clinical trials program.
(9099) Role of yoga in modulating fatigue, sleep disturbances, salivary cortisol, and immune measures in breast cancer survivors: A randomized controlled trial.
(9129) Treatment of chemotherapy-induced peripheral neuropathy (CIPN) with topical menthol: A phase I study.

Sunday, June 6, 2010

Signs Of The Times

Just a few signs I saw as I ran along Chicago's lakewalk and riverwalk this morning:

Is Agent Orange one of the culprits?

By the way, I highly recommend Cancer Girl's blog, especially right now since she is at ASCO too. She's funny and insightful. We met her and her runner husband yesterday and were delighted.

Saturday, June 5, 2010

Innovative Treatment for Relapsed and Newly-Diagnosed Myeloma

Friday night I attended a satellite session hosted by Celgene, the makers of Revlimid and other drugs. Dr David H Vesole, of Hackensack University Medical Center, focused on the newest treatments for myeloma. He said that the two most important tools are Revlimid and Velcade (and he might as well have included dexamethasone (DEX) because it is almost always combined with Revlimid and Velcade).

The new kid on the block is all three, termed VRD. In one study it produced a response in 100% of patients, and a very good partial response (VGPR) or better in 75%. That's pretty amazing. Unfortunately, though, 15% of patients experienced severe neuropathy. Other studies suggest that low-dose DEX may work as well, and with once-weekly Velcade instead of twice-weekly, neuropathy may be reduced to a much smaller number of patients. Continued maintenance with Revlimid improves the result.

Potential newer kids on the block:
  • Carfilzomib: This is a "proteazome inhibitor" (interferes with the cell's ability to dispose of waste) like Velcade. Carfilzomib seemed to be on a fast track, but is back in phase I trials to zero in on the maximum tolerable dosage. At lower dosages it appears as effective as Velcade but with only 1% of patients experiencing severe neuropathy. At the higher dosages it may be even more effective, but neuropathy may be increased. I spoke to one person in the sales booth who thought it was still a year and a half away from FDA approval.
  • Pomalidomide: I have been on a Phase II study of pomalidomide for 30 cycles. It's an immunomodulatory drug (IMiD) with the capacity to suppress parts of the immune system, particularly myeloma cells, which are wayward plasma cells. Dr Lacy from Mayo Clinic will be presenting a talk which shows a 49% objective response rate even among patients for whom Revlimid and Velcade (both) are no longer effective. I don't know when this drug will be approved - it seems to be on a slow track, and I wonder (lacking specific knowledge) if Celgene has sufficient incentive to hurry this better drug to market as long as Revlimid is making them so much money.
Unanswered questions according to Dr Vesole:
  • Should patients be pushed toward a complete response (CR) when a good response is already obtained? Studies do suggest that they do better.
  • Is a four-drug combination better than three? The jury is still out, and one study says that they are only equal.
  • What do we do when a patient on a three-drug combination relapses?
Actual sign on a Montana interstate:
Sign on the Montana interstate

Older Patients Are (almost) Like Anyone Else

The standard of care for newly-diagnosed older patients (60 and over - is 60 elderly?) has been treatment with melphalan and dexamethasone (DEX), especially in Europe. The "novel" drugs, thalidomide, Revlimid, and Velcade have not been used for older patients as much as they might, because there was no data showing that they were safe and effective for older patients. (Are they safe and effective for anyone?) By the way I'm 69, so this is a subject dear to my rickety old heart.

Today I saw a poster discussion titled "Elderly patients with lymphoma and myeloma can effectively participate in clinical trials of novel agents." Duh. Also, a recent Italian study shows that Revlimid added to melphalan and DEX improves the response rate and probably the overall survival. Further, when Revlimid was added as maintenance, the progression-free survival was significantly enhanced over melphalan and DEX alone. Another trial showed a similar advantage when Velcade was added to melphalan and DEX instead of Revlimid. Just like regular folks.

Some precautions may be necessary. Researchers have developed several different procedures for assessing a patient's physical and functional capacity. They find that function (ability to live independently) is an independent predictor of survival. Other serious health problems (heart, diabetes, etc.) also predict poor survival.

Some nuggets from a session titled: "Geriatric Oncology: The older Cancer patient":
  • "Cure" means to live long enough to die of something else.
  • Many older patients have five or more OTHER serious illnesses.
  • Older patients do not necessarily experience higher toxicity from novel drugs.
  • One speaker said we need more studies, and then "Please hurry - I'm aging fast!"
  • "Older" means 60 to 79. No one even thinks about people over 80. You're on your own.
  • Yet the median age for newly-diagnosed patients is about 65 (I think, my comment).
  • For patients over 75, use reduced dosages, e.g. thalidomide 50 mg instead of 100 or 200.
  • For relapsed/refractory patients, try all of the approved drugs, and when all else fails, put them on a trial! (Just like anyone?).
So, if the definition of cure is to live long enough to die of something else, then we most-mature adults have a much greater chance of being cured. Celebrate that!

Lunch aboard Amtrak: Spinach salad with cold salmon. Tasty, healthful, and served graciously. About $9.00.
Lunch on Amtrak

Friday, June 4, 2010

ASCO Headline: Maintenance Works

And so does consolidation. This may be the most important new information for myeloma patients this weekend.

ASCO is the American Society of Clinical Oncology, currently holding its annual meeting at McCormick Place in Chicago, 30,000 strong. I am here as a guest of the International Myeloma Foundation (IMF), to observe the information presented by the many speakers, and to blog about it from the perspective of an ordinary patient. Yay for the IMF! And thank you. I love this stuff. But be advised: I am not a doctor, just an engineer. You should get your medical advice and even your facts from your doctor.

The ASH (American Society of Hematology) conference a half-year ago suggested that maintenance works, and ASCO confirms it. What is it?
  • Consolidation is a drug therapy given AFTER a stem cell transplant (SCT), to further reduce the tumor burden.
  • Maintenance is administration of a drug (Revlimid, Velcade, ...) for a long period AFTER a good response has been achieved from an SCT or other therapy, to keep the ugly buggers down.
I attended a session titled "Expert Perspectives in Individualized Treatment of Hematologic Malignancies" (yikes - what was I doing there?). Dr David Vesole of Hackensack University spoke on "Updates on Innovative Treatment for Newly Diagnosed and Relapsed/Refractive Myeloma. More about that in another post.


Dr Vesole cited two different studies, one using Revlimid and another using Velcade, both showing a significant advantage for consolidation. In the revlimid study, two months of Revlimid increased the percentage of patients showing a very good partial response (VGPR) or better from 58% to 70%. In the other study, Velcade was started at three months after the SCT, and continued for six months. After those nine months, 49% of the patients taking Velcade were still in near-CR or better, contrasted with 33% of the control group.


The brand-newest papers on post-SCT maintenance have not been presented yet, but the abstracts are available. As Dr Durie of the IMF has pointed out in a press release dated yesterday, the new studies may influence doctors toward continuing therapy (maintenance) as a means of preventing or delaying relapse. The study results are quite clear: maintenance works. One study was "unblinded," in fact, because those on the Revlimid maintenance arm were doing so much better than those on placebo. I will attend these sessions, and will report on them if I learn anything beyond what is in the abstracts.

What does this mean for us?

Unfortunately, it's both sweet and sour. In many cases, we should probably NOT enjoy a drug holiday after achieving stable disease from an SCT or other means. Instead, going on maintenance, we will incur: (1) side effects of Revlimid or Velcade; (2) the cost of those drugs, and (3) the nuisance of taking the pills or getting the infusions. But we may likely enjoy a longer period before relapse and quite possibly a longer life. Life is good - I'm in favor of it.

What about those who are already on a drug holiday? Should I start now? Is it too late to start? Ask your doctor - I don't think the studies answer that question.

No Kidding!

Wednesday, June 2, 2010

Myeloma Is Not a Chronic Disease

This post is a respectful tribute to Elizabeth Redman, who died yesterday, June 1, 2010, way too soon.

In the last year or two we have heard hopeful words about turning myeloma into a chronic disease, especially for low-risk patients, and with the "novel" treatments like Revlimid, Velcade, and the other drugs currently in trials.

BUT WE ARE NOT THERE YET, not even close. With the best of care, many of us are still dying. This is my own little list of people that I have known personally, face-to-face, mostly from support groups in Minnesota:
  • Elizabeth Redman, 2010
  • Elijah Alexander, 2010
  • Donna Costello, 2010
  • Gene Early, 2009
  • Helen Berg, 2009
  • Ken Meister, 2008
  • Mike Ohara, 2007
  • Joyce Momont, 2006
  • Donna Penrose, 2005
No doubt each of us has such a list of friends who have gone.

The point? We can't let up. New drugs like pomalidomide, carfilzomib, and the monoclonal antibodies can't come fast enough.

Stay tuned for news from ASCO, the annual meeting of the American Society of Clinical Oncology.