Chemotalk Newsletter

Chemotalk Newsletter, Vol. 15:  July 1, 2009

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Hello, July!

For those of you receiving this newsletter for the first time and wondering "Now what?!", the good news is, if you want to opt out, just email me back. I started this newsletter with a rather narrow focus, but there are so many interconnections between chemotherapy and other important health-related stories, that I've gradually expanded the range. So...If you see something interesting, I'm doing it right. If you're bored, toss it, but send me a note to let me know what you think can make it better.

So here we go ...

Over the last weekend in May, the American Society of Clinical Oncologists (ASCO) held their annual conference in Orlando. And as is always the case, a slew of important information came out in presentations given over the time of the 5-day event.

But first, a piece that appeared in the June issue of Lancet:


The human papillomavirus vaccine works for women 24 to 45 who aren't already infected by HPV, the virus linked to CERVICAL CANCER and other cervical diseases.

Dr. Nubia Munoz, of the National Institute of Cancer in Bogota, Columbia, noted that women's rising age at first marriage and increasing divorce rates have led to more widespread premarital intercourse and pairing with new sexual partners around middle age. Their study included more than 3,200 women, aged 24 to 45, with no history of cervical disease, cancer, or genital warts caused by HPV types 6, 11, 16 and 18.

The women received either the quadrivalent HPV vaccine, which protects against the four HPV types, or a placebo at day one and months two and six of the study. The women were followed for about 2.2 years and the researchers identified four cases of infection or disease in the vaccinated group, compared to 41 cases in the placebo group. That means the vaccine was 91 PERCENT EFFECTIVE AGAINST ALL FOUR VIRUS STRAINS. When they looked at only HPV types 16 and 18, the researchers found four cases in the vaccine group and 23 in the placebo group, which means the vaccine was 83 PERCENT EFFECTIVE AGAINST THOSE TWO HPV TYPES.

* * *

And in a related study that appeared in the Journal of the National Cancer Institute:


New research has found an investigational broad-spectrum CERVICAL CANCER vaccine induced strong immune responses in mice and rabbits, and protected them against human papillomavirus (HPV) type 16 for four months.

Current HPV L1-based vaccines provide almost 100 percent protection against the two types of HPV that cause 70 percent of all cervical cancer cases worldwide, but they are expensive and offer only limited protection against other HPV types that cause cancer, according to the researchers. The new vaccine may help cover that gap in protection, they noted. When the candidate vaccine was used with a substance such as alum to stimulate immune response, the animals were protected against infection by HPV type 16, the study found.

"Clinical studies are warranted" to assess the safety of these types of vaccines," wrote Richard Roden, of the Johns Hopkins University in Baltimore, and colleagues. If this new type of vaccine proves effective, "...its simpler manufacturing process could make the local production of such a vaccine highly feasible, which might achieve the goal of producing it at sustainable prices in emerging countries and lead to its widespread implementation in the developing world," the researchers said.

A broad-spectrum HPV vaccine could solve the shortcomings of current vaccines -- they're too expensive to be used in much of the world and they don't protect against enough HPV types -- Dr. F. Xavier Bosch, of the Catalan Institute of Oncology in Barcelona, Spain, wrote in an accompanying editorial.

The results of this study " the door to a novel family of second generation HPV vaccines with significant potential value in the public health horizon. As soon as appropriate, Phase 1 trials in humans should be initiated," Bosch wrote.

* * *

Two other studies presented at ASCO could represent advances in the treatment of CERVICAL CANCER. In one study, led by Dr. Alfonso Duenas-Gonzalez of Mexico's National Cancer Institute, researchers found that adding the chemotherapy drug gemcitabine (Gemzar) to standard chemo and radiation therapy improved both progression-free and overall survival -- but not without notable side effects.

And for women diagnosed with early-stage cervical cancer, the more specific and less invasive prognostic indicator called sentinel-node biopsy appears just as effective as removal of lymph nodes in the pelvis, according to French researchers at George Pompidou European Hospital, Paris. According to the researchers, opting for biopsy rather than lymph node removal should make tracking the disease much less onerous for patients.

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Now, to the ASCO convention news:


On the bad news front, one study presented at the briefing found that use of the CA125 biomarker to track OVARIAN CANCER did not help guide treatment decisions for women. Ovarian cancer remains one of the most deadly malignancies primarily because it is typically spotted too late for treatment to be effective. Recently, however, some doctors have turned to blood levels of a molecule called CA125 to screen for the presence of disease, with repeat screens after treatment to gauge the likelihood of a recurrence.

But the new study found that even when CA125 indicated the possibility of cancer relapse and spread, starting additional treatment early did not enhance a woman's survival versus waiting longer for second-line treatment. For this study, 265 women whose ovarian cancer was in remission after one round of chemotherapy began a second round of chemo as soon as their CA125 levels started to rise. Another 264 women waited until actual signs of a relapse appeared to begin second-line therapy. This meant that, "... patients who were in the early treatment arm started their second-line chemotherapy (based on rising CA125 levels) 4.8 months earlier than those who had waited till signs and symptoms," according to study author Dr. Gordon Rustin, a professor of oncology at Mount Vernon Cancer Center in Hertfordshire, U.K.

But average overall survival was the same, whether treatment had been guided by CA125 levels or not: 41 months from the completion of the first course of therapy. "Even more interestingly, the time to third-line therapy was 4.6 months earlier in the earlier-on group," he added. "This indicated that the early initiation of chemotherapy did not induce a longer remission and, despite all this early treatment, did not improve survival."

On the plus side, the findings suggest that rising CA125 levels may not be as dire a marker as once thought, according to the researchers. "For the first time, women can be reassured that there's no benefit from early detection from routine CA125 and they can be told that even if CA125 rises, chemotherapy can be safely delayed until they have signs or symptoms of recurrence," Rustin said. "For the first time ever, women now have informed choices to be able to decide [on testing]. Most of my patients, when given this information, do not want routine CA125 measurements."

The study strikes yet another blow to the notion that CA125 might be the reliable ovarian cancer test everyone is looking for. For example, research published in the April issue of Obstetrics & Gynecology found that combining the CA125 test with transvaginal ultrasound did not help detect ovarian cancer. The new results may only reinforce that skepticism. "We've put that one [CA125 screening] in the grave so many times it has a zombie-like existence," said Dr. Kelly Marcom, a breast oncologist with Duke Comprehensive Cancer Center and director of the Duke Hereditary Cancer Clinic in Durham, N.C. Still, "I doubt every treating oncologist will stop using this to follow treatment." Another oncologist agreed. "This study suggests that early detection of metastatic cancer did not improve survival," said Dr. Claudine Isaacs, a medical oncologist with Georgetown's Lombardi Comprehensive Cancer Center in Washington, D.C. Unfortunately, the usefulness of CA125 in initial cervical cancer screening remains "questionable."

But there was good news at the meeting for women battling tough-to-treat BREAST CANCERS. Two new studies found promising results with an entirely new class of drugs, called PARP inhibitors -- the first targeted therapy for so-called "triple-negative" breast cancer. Currently, the 15 percent of breast cancer patients who have this type of aggressive tumor have only the option of surgery and chemotherapy. Breast cancers associated with the BRCA1 and BRCA2 gene mutations (which heighten risk) are almost always triple negative, explained Dr. Joyce O'Shaughnessy, lead author of one of the studies and co-director of the Breast Cancer Research Program at Baylor-Charles A. Sammons Cancer Center in Dallas.

About 30 percent of women with triple negative cancer experience a recurrence and, once that happens, only survive a year or so. In this phase II trial, half of the 120 women with this form of metastatic breast cancer were randomized to receive chemo alone, the other half to chemo plus the PARP inhibitor BSI-201. Those receiving the combination therapy saw almost a doubling of their survival -- from 5.7 months with chemo alone to 9.2 months when BSI-201 was added in, as well as about a 60 percent reduction in the risk of dying from the disease. There were also no additional side effects as compared with standard chemo.

The second phase II PARP inhibitor trial involved 54 women with advance breast cancer who carried the BRCA1/2 mutations. In this trial, the inhibitors -- especially at the higher of two doses -- succeeded in targeting the weakness in the genes' DNA repair mechanism without affecting healthy cells. Forty-one percent of patients saw their tumors completely disappear, said a British team from Kings College, London. There was a slightly lower response rate in the lower-dose group. Mild nausea and fatigue were the most common side effects. "The drugs are given orally and it still remains a question as to whether the drugs' benefits will extend beyond this narrow patient population," noted Dr. Eric Weiner, head of ASCO's communication committee and chief of women's cancers at the Dana Farber Cancer Institute in Boston. "These two studies are very exciting," Marcom said. "It speaks to a really clever understanding of the biology of the cancer."

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A few months before I was diagnosed with cancer, I offered a kidney to a friend. Fortunately, somebody else offered first and was accepted - "fortunately", because had my kidney been accepted and the cancer not detected before my kidney was implanted, I would have been the donor of a gift that potentially could kill, instead of heal.

I was over 60 at the time, but the hospital where my friend was being treated said that in making the determination, my overall health would trump my age. My kidney probably wouldn't last as long as the kidney donated by a 20-year-old, but if it was healthy, it would be better than nothing.

I'm not saying "Go out and donate an organ," but I'm including the following story, in case any of you have ever thought about donating...


By Serena Gordon, HealthDay Reporter

Nearly one of every two people over the age of 60 who are hoping for a kidney transplant will die while on the waiting list, new research shows.

The study also found that other factors, such as having diabetes, being black, having certain blood types, being older than 70, or waiting for a transplant in certain areas of the country increased the odds that someone would die while waiting for a donated kidney.

"The prognosis, particularly for older patients waiting for a kidney transplant, has deteriorated rapidly over the past decade," said study author Jesse Schold, an assistant professor of medicine at the University of Florida in Gainesville.

"Wait-list times have increased, but the rate of transplant hasn't increased markedly," he explained, adding that this leaves "older candidates at a significantly greater risk, because they have a higher risk of mortality in general."

Results of the study were published in the June 18 online edition of the Clinical Journal of the American Society of Nephrology.

Schold said the findings emphasize the need for people to get on transplant waiting lists immediately. "If you know this is something you're interested in, get on a waiting list before you even start dialysis, if possible," he advised.

Dr. Robert Provenzano, chief of nephrology for St. John Hospital and Medical Center in Detroit, agreed that people should get on a waiting list as soon as possible and consider getting on the waiting list at more than one medical center to improve the odds of getting a donated kidney.

The current study looked at data from 1995 through 2007 and included 54,669 candidates who were older than 60 and on a waiting list for a kidney transplant. Of those listed in 2006 and 2007, the researchers projected that 46% would die while on the waiting list. In 1995, that number was just 22%, according to the study. Those over 70 fared even worse, with 52% expected to die before receiving a kidney transplant.

The researchers found a wide disparity -- from 6% to 81% -- in the risk of dying while on the waiting list from region to region. The areas with the lowest death rates while on the waiting list include Alaska, Hawaii, Idaho, Montana, Oregon and Washington. Areas with the highest deaths for people over 60 while on the kidney transplant list include California, Arizona, Nevada, New Mexico and Utah.

The study also found a racial disparity, with 62% of blacks expected to die while waiting for a kidney transplant. Schold said that it can be harder for blacks to find a good matching donor under the current allocation system, and that donations tend to be lower within minority groups. But, he added, these factors are improving.

Other factors that increased the rate of death while on the transplant list included having blood type B or O, having diabetes, or already being on dialysis at the time you're put on the transplant list.

Both Schold and Provenzano said the findings highlight THE NEED TO REACH OUT MORE TO LIVING DONORS, because the need for donated kidneys far exceeds the number of donations obtained from the deceased. Even if your loved one isn't an exact match, it's possible your doctor may be able to find a paired donation in which your willing donor gives his or her kidney to someone else, and that person's loved one gives his or her kidney to you. Recently, some medical centers have created living donor chains (UCLA, for one) that have an even greater potential to increase the number of transplants.

"Be proactive in navigating the steps needed to get a transplant, and consider the center that's in your best interest. You have choices," Schold said. Provenzano also said it's critical to "...take care of yourself. Sometimes people on dialysis continue to be their own worst enemy by pushing off dialysis appointments. But, the more dialysis, the better. If you can get on night-time dialysis or home dialysis, you'll probably do significantly better."

* * *


A new study indicates that nonsurgical treatment of severe gum disease may alleviate some of the symptoms of rheumatoid arthritis in people suffering from both conditions.

"It was exciting to find that if we eliminated the infection and inflammation in the gums, then patients with a severe kind of active rheumatoid arthritis reported improvement on the signs and symptoms of that disease," says Nabil Bissada, DDS, chairman of the department of periodontics at the Case Western Reserve University School of Dental Medicine. "It gives us new intervention."

The study by Bissada and colleagues is published in the Journal of Periodontology.

Bissada, Ali Askari, MD, chairman of the department of rheumatology at University Hospitals in Cleveland, and colleagues studied 40 people with moderate to severe rheumatoid arthritis as well as severe periodontal disease.

Half the participants received nonsurgical therapy for their severe periodontal disease and instructions on good oral hygiene. The other half received no periodontal therapy. All the participants were taking traditional DMARDs for rheumatoid arthritis such as methotrexate, Plaquenil, Arava, and Azulfidine, and half were also taking a biologic therapy such as Enbrel, Humira, or Remicade.

After six weeks, the researchers noted improvement in disease severity and level of an inflammation marker in people who got periodontal therapy.
The study concludes that "Non-surgical periodontal therapy had a beneficial effect on signs and symptoms of RA, regardless of the medications used to treat this condition."

Askari notes that this isn't the first time that gum disease and rheumatoid arthritis have been linked. "From way back, rheumatologists and other clinicians have been perplexed by the myth that gum disease may have a big role in causing systematic disease," he says in a news release.

Askari says the results of the study should prompt rheumatologists to encourage their patients to be aware of the link between gum disease and rheumatoid arthritis. Gum disease, he adds, tends to be common in people with rheumatoid arthritis.

* * *


PML (Progressive Multifocal Leukoencephalopathy) CASES ASSOCIATED WITH

Rituximab is one of three monoclonal antibodies associated with PML.

In a series of progressive multifocal leukoencephalopathy cases among HIV-negative patients treated with rituximab, researchers found a 90% case-fatality rate, with a 100% case-fatality rate among those patients diagnosed with PML within three months after the last dose of rituximab.

Researchers from the Research on Adverse Drug Events and Reports (RADAR) project examined the link between the monoclonal antibody rituximab and progressive multifocal leukoencephalopathy (PML) in patients with anemia, RHEUMATOID ARTHRITIS and LYMPHOMA. The report, published in Blood,included 57 cases of rituximab-associated PML.

“These patients presented with an inability to do crossword puzzles, had problems speaking and had difficult word-finding; these are not obvious presentations and may be overlooked in many people,” Charles Bennett, MD, A.C. Buehler professor in economics and aging at Northwestern’s Feinberg School and hematologist and oncologist at the Jesse Brown VA Medical Center in Chicago, told HemOnc Today.

Rituximab is one of three monoclonal antibodies associated with a risk for PML. Natalizumab (Tysabri, Biogen Idec) was removed from the market for a year and a half, and efalizumab (Raptiva, Genentech) was also recently removed due to cases of PML associated with the drug.

According to Bennett, more attention should be paid to the link between rituximab and PML.

Using data from the FDA, the drug manufacturer, physicians and a literature review from 1997 to 2008, Bennett and colleagues reviewed cases of PML that occurred in patients treated with rituximab. The median patient age was 61, and all patients were HIV-negative.

Patients with PML received a median of six rituximab doses prior to diagnosis; the median time from last rituximab dose to PML diagnosis was 5.5 months. Patients presented with confusion/disorientation, motor weakness/hemiparesis, poor motor coordination and speech or vision changes. Most cases were identified with MRI and JC virus detection in the cerebrospinal fluid or by brain biopsy or autopsy.

The fatality rate among PML cases diagnosed within three months of last rituximab dose was 100% compared with 84% among PML cases diagnosed more than three months after last rituximab dose, yielding a case-fatality rate of 90%.

“It’s important that both patients and doctors know of the link between PML and rituximab. As rituximab therapy diffuses outside of oncology to nonmalignant or noncancer fields, doctors will be less familiar with rituximab and PML, so there is a good chance there will be an important educational and safety need for this very important drug,” Bennett said.

(This is cool...) The RADAR project began in 1998 and is comprised of a multidisciplinary team based at Northwestern University, though the group is connected internationally. Their goal is to identify, understand and report on hematology/oncology–related near-fatal adverse drug reactions. According to Bennett, this is particularly difficult in oncology due to the toxic nature of most cancer treatments and requires a high level of expertise and physician know-how.

Currently, Bennett and his colleagues at the RADAR project are working to help Genentech further explore the association between rituximab and PML. They hope to complete a large, international, prospective, case-control, epidemiologic study to identify risk factors for PML.

* * *


A new drug to treat RHEUMATOID ARTHRITIS reduces joint inflammation in severe cases while causing only mild to moderate side effects, according to a report from the first clinical trial of the drug on humans.

Masitinib, which is being developed by AB Science pharmaceuticals, is supposed to halt the activity of mast cells, a part of the immune system believed to be involved in the start and progression of RA. The French trial involved 43 people with arthritis that other treatments failed to help.

"We are encouraged from this study that masitinib not only appears to be effective, but that within the first three months of treatment, the worst of its side effects were over, possibly making it suitable for long-term treatment regimens," one of the researchers said. The next step will be placebo-controlled trials.

* * *

To end this month's newsletter on a bright note ...


By Charlene Laino, WebMD Health News

For the first time, a vaccine that trains the immune system to seek out and attack cancer cells has been shown to shrink tumors in people with melanoma.

In a study of 185 melanoma patients, the experimental vaccine also extended the time that people remained free of cancer.

There are even indications that people given the vaccine live longer, but patients need to be followed longer before researchers can be sure, says Patrick Hwu, MD, head of melanoma medical oncology at the University of Texas M.D. Anderson Cancer Center in Houston.

Unlike the vaccine that helps prevent cervical cancer in healthy women, the melanoma vaccine is designed to help people who already have cancer. The vaccine is given along with interleukin-2, or IL-2, the standard treatment for melanoma. IL-2 stimulates the immune system to attack and kill cancer cells. Tumors shrink in one in four patients with advanced melanoma who get this treatment.

The vaccine contains a substance, called gp100, that is on the surface of melanoma cells. The idea is that the immune system will see this as a threat and incite an even stronger attack against cancer cells. "The vaccine is capable of taking immune system soldiers to boot camp. Then, interleukin-2 multiplies them into an army," said Hwu.

Melanoma is the deadliest form of skin cancer. This year in the U.S., there will be an estimated 68,720 new cases and 8,650 deaths from the disease, according to the American Cancer Society.

In the study, people with advanced melanoma were given the vaccine or a placebo injection, followed by four days of intravenous interleukin-2 treatment. This was repeated every three weeks until the tumor shrank or the cancer progressed.

Tumors shrank in 22% of patients given the vaccine plus interleukin-2, compared with 10% of those given interleukin-2 alone. The vaccine also extended the time until the cancer started growing, from about one-and-a-half months for interleukin-2 alone to nearly three months for the one-two punch.

That may not sound like much, but cancer advances are made in baby steps, says Len Lichtenfeld, MD, deputy medical director of the American Cancer Society.

Lichtenfeld tells WebMD that there's reason for "cautious optimism." A lot of cancer vaccines that seemed promising in early studies haven't panned out, he says.

Louis M. Weiner, MD, head of the Lombardi Comprehensive Cancer Center in Washington, D.C., says the vaccine study is the latest in a series showing that the immune system can be mobilized to attack cancer. "Many of us believe that a combined approach that includes an immune system attack on cancer cells will ultimately prove to be most useful in controlling cancers such as melanoma."

Hwu says the next step is to try to reproduce the findings in a longer, larger study. Also, his team hopes to add yet another punch -- in the form of an agent that takes the brakes off the immune system. Then, the immune system soldiers can proliferate with impunity, hopefully killing even more cancer cells, he explains.

* * *

And last, but definitely not least ...


Palladia (toceranib phosphate) is the first drug to be approved by the U.S. Food and Drug Administration specifically to treat CANCER in dogs, the agency said in a news release Wednesday.

The drug has been sanctioned to treat canine cutaneous mast cell tumors, which account for about one in five cases of skin tumors in dogs.

While these tumors may appear small, they can be life-threatening if not treated and removed, the FDA said. Palladia, among a class of drugs called tyrosine kinase inhibitors, kills tumor cells and cuts off the tumors' blood supply.

The drug's side effects may include diarrhea, loss of appetite, weight loss and bloody stools.

Palladia is produced by New York City-based Pfizer Animal Health Inc.


And if you have any thoughts of how this newsletter could be improved, please email me directly, at

Elaine Jesmer

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