Unraveling the complexities of myeloma therapy

BY GUEST BLOGGER | DECEMBER 14, 2009

Diane Gambill, PhD, is CURE's senior scientific advisor and chief scientific officer for Physician's Education Resource and Cancer Information Group.

For years, debates over the right way to deliver therapies for cancer have included questions on whether to give one drug up front or two (or more), and whether to save your "best" drug for later if your disease returns. For myeloma, the emerging picture is that three drugs are better than two, and two are better than one such that using all your best drugs up front might be best. At this year's American Society of Hematology meeting, a plenary session paper showed that if a proven three-drug regimen is followed with additional therapy, termed maintenance therapy, patients do even better.

The study, conducted by Dr. Maria Mateos and colleagues in Spain, included 260 newly diagnosed patients who were at least 65 years old. The trial compared induction (or initial) therapy with Velcade/melphalan/prednisone (VMP) to Velcade/thalidomide/prednisone (VTP). One aim of the trial was to figure out whether you really need a type of drug called an anthracycline, so the comparator arm replaced the anthracycline melphalan with thalidomide, an immunomodulatory agent. One notable part of the design of this study was the use of Velcade on a weekly rather than twice-weekly schedule. The investigators wanted to know if by reducing the dose, they could reduce the overall adverse event profile without compromising efficacy.

The response rates were very similar between the two regimens in this part of the trial (80 percent versus 81 percent). VMP was associated with more hematologic toxicities, and VTP was associated with more cardiac toxicities. There was less Velcade-related peripheral neuropathy with the weekly schedule than you would expect to see with the twice-weekly schedule.

Once induction therapy was completed, patients in each arm were randomized to receive maintenance with either Velcade/prednisone (VP) or Velcade/thalidomide (VT). Adding maintenance therapy to the induction regimen increased the complete response rate, and the toxicity added by the extended therapy was low. The use of VT following either induction regimen improved progression-free survival by a statistically significant length of time compared to VP (not reached versus 33 months); however, this improvement did not translate into an increase in overall survival. Further, VMP followed by VT was found to be better than VTP followed by VP, which means the anthracycline (melphalan) component of induction therapy is important to keep.

The main take-home messages from this study are that a less intense regimen with follow-up maintenance therapy is safe and effective. These results reinforce the notion that duration of therapy is an important factor in getting the best results--if you can receive all of your planned therapy without dose reductions or skipping doses, your myeloma is more likely to respond--and that maintenance therapy adds to the benefit.

Trial tests new drugs, male breast cancer detailed

BY GUEST BLOGGER | DECEMBER 11, 2009

Every year, CURE invites one advocate who is attending the San Antonio Breast Cancer Symposium to serve as a guest blogger. This year readers will be hearing from Bev Parker, PhD, a 24-year breast cancer survivor who is attending the symposium for the seventh year.

Breast cancer advocates at the San Antonio symposium have many opportunities to be involved and to learn. Two of my favorites today were the I-SPY 2 trial and posters on male breast cancer.

Laura Esserman, MD, of the University of California at San Francisco, is the dedicated principal investigator of I-SPY 2, and Jane Perlmutter, PhD, is the tireless champion of advocate involvement (among many others spending countless hours on the trial). These two individuals hosted a breakfast today to educate interested advocates. I-SPY 2 features a random, adaptive, neoadjuvant design that involves testing investigational drugs in women whose locally advanced breast cancer is at high risk of recurrence.

Prior to surgery, these women will undergo standard chemotherapy, and as many as 80 percent will also be given investigational drugs. Tissue from the surgery will rapidly identify the drugs that increase the chance that no cancer remains (referred to as "pathological complete response").

Many drugs will be tried (among the first, a PARP inhibitor) and each will be tested on 20 to 120 patients, based on biomarker profiles. Patients will be followed for three to five years. This trial design allows for learning while doing, enables earlier drug approval, and drastically reduces costs.

The trial will be conducted throughout the country with about 15 open sites by May 2010. The drugs that increase the chance that women will have a pathological complete response will go into phase 3 testing. One exciting part is that advocates have been involved at every step along the way.

Male breast cancer comprises about 1 percent of breast cancer cases diagnosed each year in the U.S. Of the more than 1,000 posters presented this year at the symposium, five featured male breast cancer. One study was conducted in each of the following countries: Canada, Germany, Sweden, the U.K., and the U.S.

Below are some of the study conclusions, alphabetical by country:
>Most men were prescribed adjuvant endocrine therapy, usually tamoxifen. Despite increased use of endocrine therapy, overall survival has not changed significantly over time.
>Luminal A is the most common type of male breast cancer. It shows a significant improved outcome compared with basal-like tumors.

>No difference exists in the distribution of stage at diagnosis between male and female breast cancer.

>Subtle differences exist between male and female breast cancer regarding hormone receptor profiles.

>Men and women may share common risk factors for breast cancer. The biology of male breast cancer resembles the late onset and ER-positive type of female breast cancer.

Mortality rates for breast cancer have improved over time, but progress for men lagged behind that for women.

More tomorrow!

To read more articles from CURE's coverage of SABCS 2009, visit sabcs2009.curetoday.com.

Breast cancer in rural and urban areas

BY GUEST BLOGGER | DECEMBER 10, 2009

Every year, CURE invites one advocate who is attending the San Antonio Breast Cancer Symposium to serve as a guest blogger. This year readers will be hearing from Bev Parker, PhD, a 24-year breast cancer survivor who is attending the symposium for the seventh year.

The symposium got underway this morning with 9,000 participants, according to welcoming comments by C. Kent Osborne, MD. The day was filled with reports of fascinating research. I'll highlight the first plenary, which I found most noteworthy, and add some interesting points from other presentations.

The opening plenary was a lecture given by Valerie Beral, MD, of the University of Oxford. She discussed an epidemiological perspective on the causes and prevention of breast cancer. Rural areas in the world have much less breast cancer, but diagnoses increase rapidly with urbanization. Today, one million cases of breast cancer are diagnosed every year throughout the world. At the current rate of urbanization, that number is expected to be two million by 2040.

In rural areas, women on average have more babies, have them at younger ages, breastfeed more often, and breast feed longer than women in developed countries. Dr. Beral concluded that the incidence of breast cancer would be halved in developed countries if women maintained the same childbearing and lactation rates as those in undeveloped countries. She said that childbearing, lactation, and nutrition account for most, if not all, of the international differences in the incidence of breast cancer.

According to Dr. Beral, women in developed countries will not change their childbearing and lactation rates. However, if they maintained healthy BMIs, did not take hormone replacement therapy, and did not drink alcohol, breast cancer diagnoses would be reduced by 20 percent. To address childbearing issues, Dr. Beral stated that short-term exposure in early adulthood to hormones of late pregnancy and lactation would give lifelong protection against breast cancer. She suggested that developing a hormonal vaccine to be given at that point of life should be a goal for the large-scale prevention of breast cancer.

Below are some quick nuggets of information gleaned from various other presentation scattered throughout the day:

>BIG 1-98 showed prolonged overall survival, after a 76-month update, for women who switched from tamoxifen to letrozole after 3 to 4 years.

>The LACE study reported that 3 to 4 alcoholic drinks per week is associated with an increased risk of primary breast cancer in postmenopausal, overweight, and obese women.

>Women with a BMI greater than 25 have significantly high rates of breast cancer recurrence and death.

>Bisphosphonate use is associated with a 30 percent reduction in the risk of postmenopausal breast cancer after one year of use, and breast cancers that develop while taking bisphosphonates have a better prognosis.

>25 percent of breast cancer that is ER-negative at diagnosis can change to ER-positive at recurrence.

More tomorrow!

To read more articles from CURE's coverage of SABCS 2009, visit sabcs2009.curetoday.com.

In Other Words ... Communicating When Naked--My Perspective as a Patient

BY GUEST BLOGGER | DECEMBER 3, 2009

Helen Osborne, MEd, OTR/L, is a breast cancer survivor and the president of Health Literacy Consulting

Talking about health and other medical matters had always been easy for me. As an occupational therapist and health-literacy consultant, I felt confident and in charge of conversations no matter which professional hat I was wearing. But after a routine mammogram turned out not to be so routine, I felt more than hatless. I felt naked. Now I had to communicate not as a provider or consultant, but as a patient.

The diagnosis was DCIS (ductal carcinoma in situ, a very early-stage of breast cancer). Ironically, this was a condition I knew a good deal about. The year before, I'd written the National Cancer Institute booklet "Surgery Options for Women with Early Stage Breast Cancer". But as a patient, I became easily overwhelmed talking with doctors about my diagnosis and treatment options. Since the conversations concerned me directly, I was often so flooded with emotion that I had trouble thinking and remembering.

Conversations eventually got easier, and over time I learned what I needed to learn. I also learned, through no choice of my own, about being a patient. Here are some of the lessons I came away with after communicating "naked." Understanding them, whether you're a patient or a provider, can make a difference in how each of you works with the other.

What Patients Need to Do

Show up. This sounds so simple yet can be so hard to do. As a patient, it takes courage to show up for medical appointments when fearing news you don't want to hear or dreading procedures you don't want to have. I'd muster courage by asking my husband or friend to go with me, or having a private "pity party" before appointments and then rewarding myself later for showing up.

Some of the most courageous women I've ever met sat beside me in the waiting room when I went for radiation treatments. We chatted, but usually not about our diagnoses or prognoses. Instead, we talked about the ordinary parts of our lives, such as our commute that morning or what we did over the weekend. We supported each other yet didn't need words to share our experiences as patients.

Create your own medical record. As a health-literacy consultant, I sometimes speak to consumers about health communication. One recommendation I make is that people create their own notebooks with important medical information. But did I take my own advice? No, at least not until it felt like medical matters were way out of control. Creating my own medical record turned out to be one of the most important things I did. My medical record is in a three-ring binder that includes:
     >Medical reports. I included copies of pathology reports and discharge instructions. Having these so available not only helped me but, at times, also my providers. I remember an early-morning procedure that was almost delayed because the specialist didn't have (or couldn't find) a copy of my surgeon's referral. But thanks to my notebook, I had a copy of the report she needed.
     >Doctors. I had so many appointments at different facilities that sometimes I felt like a "secret shopper" of medical matters. To keep track of all these providers, I had a section in my notebook for information about each doctor, including a photo (if available), contact information, and directions to his or her office.
     >Questions. At home, I could think of lots (and lots) of questions I wanted to ask my doctors. But when wearing just a hospital johnny, I struggled to remember any of them. To help, I would make a list of all my questions beforehand so that later all I needed to do was write down the answers.
     >Notes to me. I found it comforting to write occasional notes and stories about how I felt and what I observed. Not only did they defuse my emotions at the time, but now these notes serve as powerful reminders of my patient experience. I didn't know then what I would do with them, but now they're the core of what I'm writing to you.
     >Important papers. Many providers asked me similar questions about medications and allergies. I got tired of repeating myself, and so I made a master medication list which each office could copy. I also kept my signed healthcare proxy in the notebook for any health provider who requested it.
     >Kind words. People were amazingly wonderful. I treasure their support and caring, though honestly couldn't always remember who did what. To help, I made a list of their gifts and other niceties with space to note when I thanked them.
     >Zippered pouch. I found that a three-hole-punch zippered pouch was a most handy addition to my notebook. I used it as a catch-all for my patient identification cards and doctors' business cards. And when I got tired of fumbling around for a pen to take notes during appointments, I added one to my trusty zippered pouch.

Learn only as much as you want to know. What probably surprised me most during this time was that, as a patient, I did not want a lot of "outside" information from the Internet or books. I trusted my doctors to tell me what I needed to know. I also found outside information somewhat scary, as I tended to focus on the worst-case scenarios. I checked with other patients and learned that many of us set limits on how much information we want to have.

Be in charge of communication. Life changes forever when you are diagnosed with a serious illness. But I knew from the start that I did not want this diagnosis to be my sole identity. Being in charge of communication was an important way for me to preserve my sense of self. One way I did so was with something I called "breast-free zones." These were times (often at meals) I opted to discuss topics other than my anatomy. Setting limits on the conversation not only helped me but also others who worried about what to say.

Another way I was in charge of communication was by sending out periodic group emails to family and friends with updates about my medical matters. For the sake of everyone's privacy, I entered their addresses as "bcc" (or blind carbon copy) so others could not see who I was writing to.

Be nice to yourself. Similar to the story of Hansel and Gretel, who marked their path with breadcrumbs, I placed treats along my treatment path. Some were small, such as buying my favorite coffee on the way to radiation treatments. Other treats were bigger, including a celebratory party to toast good friends and good health.

Reprinted with permission from On Call magazine and published by boston.com/Monster, a division of Boston Globe Media. You can find all of Osborne's articles at the Health Literacy Consulting website, www.healthliteracy.com.

A preview of hot topics from the world’s leading hematology conference

BY GUEST BLOGGER | NOVEMBER 24, 2009

Diane Gambill, PhD, is CURE's senior scientific advisor and chief scientific officer for Physician's Education Resource and Cancer Information Group.

As senior scientific adviser for CURE, I am constantly looking for new, cutting-edge information from the clinical research arena that I can share with our readers. In early December, I'll be tweeting "live" from the American Society for Hematology meeting in New Orleans so that we can share this information with you as it happens! Follow us on Twitter @cure_magazine, and sign up for one of our blood cancer e-newsletters to get the latest news from the meeting. We'll give you a first look at information that is expected to change the way some blood cancers are treated and give you a glimpse at interesting research expected to improve the way we treat blood cancers in the near future. Here's a sneak peek at some of the news from this year's meeting, which starts December 5:

> Great strides continue to be made in understanding the biology and natural history of blood cancers. These advances allow clinicians to choose so-called risk-adapted treatments for patients. Interestingly, the individualized approach to managing blood cancers has fostered advances in relatively rare diseases, and it promises to be an interesting year for new treatment strategies for patients with relatively uncommon blood cancers.

> A study from Italy on acute promyelocytic leukemia (APL) was chosen for the plenary session, where the most important studies from this year's ASH meeting will be featured. APL is related to acute myeloid leukemia and the myelodysplastic syndromes. You can read more about MDS in CURE's feature, "Treatment Boost for MDS," from 2006.

> Two new drugs have recently been approved for T-cell lymphoma (TCL), a relatively rare type of lymphoma. For peripheral TCL, Folotyn (pralatrexate) is the first drug approved for this enigmatic disease. (Read more about the approval here.) There will be new information available on clinical trials with Folotyn, including how clinicians can manage adverse events from this drug. For cutaneous TCL, a new histone deacetylase inhibitor called Istodax (romidepsin) is now available, and we will hearing more about how this agent can be used in the clinic. (Read more about the approval of Istodax here.)

Look for more from CURE on these and other exciting new findings in the more common lymphomas, leukemias, and myeloma as the stories unfold the first week in December. We look forward to your comments and questions!

PARP inhibitors prime example of acceleration in drug discovery

BY GUEST BLOGGER | AUGUST 3, 2009

Diane Gambill, PhD, is CURE's senior scientific advisor and chief scientific officer for Physician's Education Resource and Cancer Information Group.

You may be wondering how PARP inhibitors burst onto the oncology scene with seemingly little prelude. The other day, CURE's managing editor, Melissa Weber, reminded me that I had made a bold prediction a couple of years ago regarding the PARP inhibitors. At the time, I was very enthusiastic about the early data on PARP inhibition, especially because the science behind it made so much sense to me (look for a feature on PARP inhibition in the next issue of CURE). I advised Melissa to keep an eye on this field for important developments in the near future. Now PARP is one of the most "Googled" cancer-related words on the Web.

The events leading up to this year's much-publicized presentation on PARP inhibitors in breast cancer (see CURE's coverage of ASCO 2009) represent the dramatic acceleration in drug development timelines. Several key advances have primed the bench-to-bedside revolution in cancer research over the past decade. Applying the power of computing to automating lab processes and analyzing large volumes of data is probably the lynch pin of the bench-to-bedside revolution. In the mid 80s, it became possible to sequence a single gene, but it could take several years to confirm just one gene sequence! With high throughput technology, the timelines are now compressed to mere days (not quite fitting into a 48-minute CSI episode ... but close).

Comparing a commonly used cancer drug, Taxol, to the PARP inhibitors brings these advances into focus. Taxol was discovered in 1967 and first presented at a research meeting the same year. This discovery was part of an NCI program established in 1955 to systematically search for natural products--essentially a hunt-and-peck method for drug discovery. It was 25 years later that Taxol was approved by the FDA for treating cancer in the clinic. (You can read more about the Taxol in The Discovery of Taxol from CURE's Winter 2006 issue).

PARP inhibition as an antitumor strategy first emerged from the laboratory around 1994. About four years ago, clinical investigations were undertaken with some of the first-generation inhibitors, and today a phase III trial is already under way. These are indeed exciting times for both researchers and patients.

Many agents now on the market have been discovered and approved on somewhat shorter timelines than Taxol, but the discovery-to-bedside timeline for the PARP inhibitors is quite remarkable--probably more so because of the promising results presented in this year's ASCO plenary session in breast cancer.

So, what about my next prediction? Stay tuned ...