Gem, tax, dox and trabectedin for LMS

I know I'm leiomyosarcoma-centric! Eventually, I hope other volunteers will report developments in treating their subtypes. In the meantime, I want to discuss some LMS news that illustrates how confusing research can be for a patient trying to decide which chemo to do.

At ASCO, a poster from the French Sarcoma Group suggested that gemcitabine (Gemzar) + docetaxel (Taxotere) is not more effective than gemcitabine alone. One reason this matters is gemcitabine is less toxic than the g+d combo.

The study divided patients into those with uterine LMS and LMS that arose elsewhere. ULMS patients had better responses in general to the chemo, a pattern seen in other studies.

In contrast, a multi-center SARC trial in 2007 found g+d more effective than g alone in metastatic soft-tissue sarcoma, including LMS.

At a discussion session, Dr. Chris Ryan of Oregon Health & Science University in Portland, OR, noted that the French study had a relatively small number of patients. He said he wished there would be random trials comparing g+d to anthracyclines as a first-line treatment. Doxorubicin (Adriamycin) is an anthracycline that is often used as the first line of defense for LMS and some other sarcomas.

Another poster, from the UK, found g+d effective as a first-line treatment for metastatic LMS. But it didn’t compare g+d to g alone or doxorubicin.

Dr. Martee Hensley of Memorial Sloan-Kettering Cancer Center in New York reported on a SARC Phase 2 trial of adjuvant chemo for high-risk ULMS. Patients get four cycles of g+d, followed by four cycles of doxorubicin. The trial isn’t finished, but judging by the early data, she said, she expects patients to do better with adjuvant chemo. (See what I wrote about adjuvant chemo for soft-tissue sarcoma in general.)

To gain a better understanding, she said, doctors could do a trial in which some women got adjuvant chemo and others did not. The ones who didn't get chemo couldn’t get a placebo because they would know from the lack of side effects. Another option would be to compare adjuvant chemo with an aromatase inhibitor, she said, or to compare one chemo against another.

Dr. Hensley discussed problems with both the AJCC and FIGO staging systems for ULMS. She wants a nomogram that combines stage-specific variables with other factors. A good staging system matters because if you enroll patients who were going to do well anyway, it influences the results of a clinical trial, she said. From an MSKCC study:

Estimates of stage-specific PFS [progression-free survival] and OS [overall survival] for uterine LMS were altered substantially when using the AJCC versus FIGO staging system. Adjuvant treatment strategies should be tested in patients at substantial risk for disease progression and death. Neither the FIGO nor AJCC staging system is ideal for identifying such patients, suggesting a need for a uterine LMS-specific staging system to better target patients for trials of adjuvant therapies.

In other ASCO news, at least three studies noted again that trabectedin (also known as yondelis) has value in treating patients with liposarcoma and leiomyosarcoma. (Click here, here and here.)
-- Suzie Siegel

Putting the "sun" in the sunflower

We swelter in the sun at fundraisers, hoping to spread the word about services for people affected by sarcoma. This photo shows Judy Lehman, a retired school nurse practitioner, who helped me staff a table at Miles for Moffitt in Tampa last month.

More than 3,000 people participated in the race to raise money for research at the Moffitt Cancer Center, including a team called the Sarcoma Speed Demons.

Although the Sarcoma Alliance needs to raise money for itself, and we have our own fundraisers, we welcome the chance to participate in any event where we can give people information.

At Miles for Moffitt, I was grateful to the University of South Florida students who provided antiseptic gel, gloves and water so that I could catheterize in a portable toilet. (I had left my house without the proper supplies.) As more people with cancer survive, we will need to keep in mind their health needs as we plan events.

An example of that is Moffitt's fundraiser for sarcoma research July 18. We had planned on a morning at the beach, but the weather has been so scorching that the staff decided instead on bowling in air-conditioned comfort. Come join us! -- Suzie Siegel

With help from our friends

Last year, my friend Susan Snyder and her life partner, Doug Murray, cycled through the Columbia River Gorge as part of Jackson's Ride the Gorge, a fundraiser for the Northwest Sarcoma Foundation. At the start of the ride, they wore T-shirts with my photo and "Cruisin' for Suzie" written under it. On the back was a kid on a tricycle, looking over his shoulder and sticking out his tongue. He says, "Take THAT sarcoma!"

It is great to have friends. It is even better to have friends with a sense of humor.

This year, the event will be July 18. Melissa Hill, the foundation's executive director, has been very supportive of the alliance. Also, please check out Susan's blog, Nature's Call.

-- Suzie Siegel

Adjuvant chemo

Medical oncologists in sarcoma still disagree over the value of adjuvant chemo for many subtypes, and that was apparent in a discussion at ASCO last month. The ASCO Daily News reported on it, but I'll add in some of my own notes.

Dr. George Demetri of the Dana-Farber Cancer Institute in Boston talked specifically about GIST, and if you're interested, I encourage you to click on the Daily News link above. The other two doctors in the session talked about chemo in general for other subtypes.

Session Chair Ian Robert Judson, MD, of the Royal Marsden Hospital, United Kingdom, noted that questions arise about the appropriateness of adjuvant therapies because of several factors. Soft tissue sarcomas are rare diseases, he explained, and there are conflicting data on the efficacy of chemotherapy as well as variations in clinical practice regarding the standard treatment for these diseases. ...

“We know that there are variations in response to these treatments among individuals, and unless we learn more about how to identify who is likely to benefit, we run the risk of administering a lot of unnecessary treatments with accompanying toxicity,” said Dr. Judson in an interview with ASCO Daily News.

He noted that the physician must take into account the individual patient’s level of risk tolerance, along with the best available evidence regarding the likelihood of benefit when deciding whether to initiate adjuvant therapy for these malignancies.

Robert S. Benjamin, MD, of M. D. Anderson Cancer Center, reviewed recent literature regarding adjuvant chemotherapy for soft tissue sarcomas. He noted that the Sarcoma Meta-analysis Collaboration in 1997 found that doxorubicin-based chemotherapy improved time to local and distant recurrence and overall recurrence-free survival; however, there was not a significant improvement in overall survival.

After the 1997 study, ifosfamide was added to doxorubicin, and that improved survival a little, he noted. Since then, other drugs have been developed or tried with sarcoma. He criticized a 2007 study by the EORTC, saying it was not representative of a global, random population.

He recommends neoadjuvant chemo, if possible, because it lets the oncologist judge whether the tumor is reacting to the chemo. In regard to adjuvant chemo, he would like to see doctors give more of it for a longer period of time.

“I don’t put much stock in the argument that chemotherapy doesn’t work,” he said. “We know that, yes, it works and no, it doesn’t work nearly well enough. So we need to give more of it, not less. Stage III sarcomas are such a bad group of tumors that, even though we know the treatment is going to be awful for the patient, not treating them is ethically unacceptable.”

Dr. Benjamin suggested that clinicians should not approach adjuvant therapy for soft tissue sarcomas using the same rules for breast cancer therapies because of broad differences between the diseases.

He noted that breast cancer is more common and more homogeneous than sarcoma and therefore results in larger studies and more numerous therapies, whereas there are limited options for sarcoma.

An abstract from the French Sarcoma Group, presented at last month's ASCO, found little benefit for grade 2 patients, but improved survival for those with grade 3.

-- Suzie Siegel

Different NCCN standards

        If a woman gets diagnosed with an abdominal sarcoma, her oncologist can check the National Comprehensive Cancer Network's soft-tissue sarcoma guidelines, written by some of the top doctors in sarcoma centers across the United States.

        If a woman gets diagnosed with the same sarcoma subtype in her uterus, her oncologist will be steered to the uterine neoplasms guidelines, written by top gynecologic oncologists.   

        The guidelines for uterine sarcomas recommend a patient get a physical exam every three months for two years, plus a chest X-ray annually. "CT/MRI as clinically indicated." This replaced the previous recommendation of: "Chest/abdomen/pelvis imaging every 3-6 mo for 2 y, then annually."

        Meanwhile, the soft-tissue sarcoma guidelines recommend a physical exam, plus CT scans of the abdomen/pelvis, every 3-6 months for 2-3 years for someone whose tumor started in the abdomen. "Consider chest imaging." These guidelines also have much more information on new drugs and genetics for sarcoma.

         I don't understand why there are different standards, nor do I understand why chest imaging is not recommended more highly, considering that some subtypes migrate to the lungs. 

        In 2005, I asked Dr. Robert Benjamin about the NCCN guidelines, and he said sarcoma doctors would write the ones for uterine sarcomas in the future. That future has not yet come. 

      -- Suzie Siegel

SARC creating unified database

          SARC will build a database of tissue specimens stored at M.D. Anderson Cancer Center in Houston. The WWWW Foundation has more information: 

The QuadW board and the Tichenor family have combined to provide a three-year $687,500 grant to the Sarcoma Alliance for Research through Collaboration (SARC) to create a unified clinical trial database system.

The database will consolidate findings from the clinical trials of multiple research institutions, allowing remote data entry and access for current trials. Researchers will be able to customize the user interface to suit individual trials and access data from previous trials and combine it in flexible ways with current research data.

SARC is a primary resource for sarcoma researchers and clinicians. As a collaborative effort of leading cancer centers, SARC guides the development of clinical trial protocols and provides a forum for reporting and evaluating the results of those trials.

          SARC Treasurer Bob Benjamin, chair of Anderson's Sarcoma Center, discussed the database last month before the annual meeting of the American Society of Clinical Oncology (ASCO) in Orlando. Dr. Benjamin said the data should be collected this year, with tissue samples and imaging tests gathered together next year.

          I'm grateful to those who made this happen. If you want more information on the need for tissue banks, I wrote this article previously. -- Suzie Siegel

Women under-represented in clinical trials

This is a news release from the University of Michigan, and I'm posting it verbatim because I think it's really interesting. -- Suzie Siegel

Women are under-represented in clinical cancer research published in high-impact journals, according to a new study by researchers at the University of Michigan Comprehensive Cancer Center.

Taking into account the incidence of particular types of cancer among women, studies included a smaller proportion of women than should be expected. The analysis looked specifically at studies of cancer types that were not gender specific, including [sarcoma,] colon cancer, oral cancers, lung cancer, brain tumors and lymphomas.

The authors looked at 661 prospective clinical studies with more than 1 million total participants. Results of this study appear online in the journal Cancer and will be published in the July 15 print issue.

“In the vast majority of individual studies we analyzed, fewer women were enrolled than we would expect given the proportion of women diagnosed with the type of cancer being studied. We’re seeing it across the board in all cancer types,” says study author Reshma Jagsi, M.D., D.Phil., assistant professor of radiation oncology at the U-M Medical School.

“It’s so important that women are appropriately represented in research. We know there are biological differences between the sexes, as well as social and cultural differences. Studies need to be able to assess whether there are differences in responses to treatment, for example, between women and men,” she adds.

The National Institutes of Health’s Revitalization Act of 1993 explicitly calls out the importance of including women in clinical research, noting that clinical trials should enroll adequate numbers of women to allow for subgroup analysis.

The U-M researchers found that studies reporting government funding did include higher numbers of women participants, but the impact was modest – 41 percent, compared to 37 percent for studies not receiving government funding.

Traditionally, researchers were told not to include people of vulnerable populations in their studies. This group included women of childbearing age. “By protecting them from research, we’re excluding them,” Jagsi notes.

Previous studies have found some barriers to clinical trial participation are lack of information, fear and a perception of interfering with personal responsibilities, such as child care.

“Sometimes participating in research studies can be time intensive. Women today are often stretched very thin trying to deal with the balance between domestic responsibilities, their cancer diagnosis, and often a career as well. They may be particularly likely to find clinical trials too burdensome. In that case, researchers should consider providing compensation to help with transportation or child care expenses,” Jagsi says.

This under-representation of women is not necessarily the result of conscious decisions, points out senior author Peter Ubel, M.D., director of the Center for Behavioral and Decision Sciences in Medicine at U-M.

“Clinical researchers are not purposely trying to exclude women from their studies. All the more reason they need to consciously and earnestly revise their recruitment methods to give more women a chance to volunteer,” Ubel says.

Methodology: The researchers looked at all original clinical cancer research published in five top oncology journals and three top general medical journals in 2006. The journals included were the New England Journal of Medicine, the Journal of the American Medical Association, the Lancet, the Journal of Clinical Oncology, the Journal of the National Cancer Institute, Lancet Oncology, Clinical Cancer Research and Cancer. Articles were analyzed to determine factors including the number of participants, gender of participants, type of cancer and funding source.

The percent of women was summarized in two ways: The overall percent of women from all studies; and the average percent from each study that were women. The first method gives greater weight to larger studies, while the second method allows each study to have equal weight. Women’s representation was lower than expected, based on general population incidence data, according to both analyses.