National Cancer Institute NCI Cancer Bulletin: A Trusted Source for Cancer Research News
January 11, 2011 • Volume 8 / Number 1

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250th Issue

NEWS

Continued Shortage of Chemotherapy Drugs Causing Concern

A serious shortage of commonly used chemotherapy drugs that began several years ago and worsened in 2010 is taking a toll on medical facilities and causing concerns among patients and doctors alike, according to representatives from government and professional groups. The continued shortfall is part of a more widespread shortage of drugs, including those frequently used in anesthesia and to treat dangerous infections, and has raised anxiety about patient care and clinical trials in which the drugs, many of them generic, are important components of treatment. Read more > >

COMMENTARY

Inside NCI: A Conversation with Dr. Barry Kramer about Cancer Screening

Watch the Inside NCI videoThe editor-in-chief of NCI's Physician Data Query (PDQ) Screening and Prevention Editorial Board talks about the types of effective cancer screening tests available and the risks that are sometimes associated with cancer screening. See the video > >

  

A MESSAGE TO READERS

View the 2010 NCI Cancer Bulletin reader survey results.

IN DEPTH

UPDATES

  • Notes

    • NCI Director Announces New Senior Staff Member
    • Recap of Last Month's President's Cancer Panel Meeting
    • In Memoriam: Susan Lowell Butler
    • 250 Issues and Counting!

Selected articles from past issues of the NCI Cancer Bulletin are available in Spanish.

The NCI Cancer Bulletin is produced by the National Cancer Institute (NCI), which was established in 1937. Through basic, clinical, and population-based biomedical research and training, NCI conducts and supports research that will lead to a future in which we can identify the environmental and genetic causes of cancer, prevent cancer before it starts, identify cancers that do develop at the earliest stage, eliminate cancers through innovative treatment interventions, and biologically control those cancers that we cannot eliminate so they become manageable, chronic diseases.

For more information about cancer, call 1-800-4-CANCER or visit http://www.cancer.gov.

NCI Cancer Bulletin staff can be reached at ncicancerbulletin@mail.nih.gov.

Featured Article

Continued Shortage of Chemotherapy Drugs Causing Concern

A serious shortage of commonly used chemotherapy drugs that began several years ago and worsened in 2010 is taking a toll on medical facilities and causing concerns among patients and doctors alike, according to representatives from government and professional groups. The continued shortfall is part of a more widespread shortage of drugs, including those frequently used in anesthesia and to treat dangerous infections, and has raised anxiety about patient care and clinical trials in which the drugs, many of them generic, are important components of treatment.

“We’ve heard a crescendo of complaints and concerns,” said Dr. Michael Link, a pediatric oncologist from the Stanford University School of Medicine and president-elect of the American Society of Clinical Oncology (ASCO). It’s not possible to quantify the extent of the impact on patient care, Dr. Link noted, but, based on what’s known, “it’s the worst shortage we’ve experienced in three decades. In terms of scope, it’s huge.”

All of the chemotherapy drugs involved in the shortage are in a category known as sterile injectables, explained Valerie Jensen, associate director of the Drug Shortage Program in the FDA’s Center for Drug Evaluation and Research. Sterile injectables, in fact, account for 77 percent of the overall shortage.

Drug shortages in the United States have worsened in the last 5 years, particularly in 2009 and 2010. Although drug shortages in the United States have continued to worsen over the past 4-5 years, the number of sterile injectables in short supply—particularly common chemotherapy drugs—increased dramatically from 2009 to 2010. (Data courtesy of FDA's Center for Drug Evaluation and Research)

Although production and quality issues have been chief reasons for the shortage, the problem can also be traced back to the business realities of manufacturing pharmaceuticals, Ms. Jensen explained via e-mail. This is particularly the case for sterile injectable chemotherapy drugs.
 
She explained that there used to be an adequate number of manufacturers for many of these sterile injectable drugs, but in recent years many of these companies have opted to stop producing the drugs “in favor of newer, more profitable products,” Ms. Jensen continued, “since firms have a limited number of production lines and can only make a certain number of products on the lines they have.”

For example, although eight companies had approval to produce leucovorin at one point, until very recently only two companies were still manufacturing the drug. The FDA recently granted another company approval to begin producing leucovorin, Ms. Jensen noted.

Cooperatively Tackling the Problem

In November, spurred by the extent of the problem and the lack of any relief in sight, ASCO co-sponsored a meeting with the American Society of Health-System Pharmacists (ASHP), the Institute for Safe Medication Practices (ISMP), and the American Society of Anesthesiologists to analyze the causes of the shortage, how best to address it, and how to prevent or mitigate such problems in the future. Officials from NCI and the FDA—who, like officials from ASHP, are closely tracking the shortage and have  a Web site that is updated daily with new information on the status of the drugs in short supply—attended the summit. A report of the proceedings was released on January 10.

In the meantime, medical facilities and providers are doing their best to deal with the shortages. It’s clear, however, that the situation is taking a toll, particularly on smaller practices and centers. According to an ISMP survey of 1,800 health care professionals conducted in September, the risk of medical errors is on the rise as hospitals and other health care facilities cope with issues such as dosing or frequency of administration when forced by the shortage to use alternative drugs. More than one-third of respondents said the shortage had led to a medical error that could have harmed a patient.

For example, the drug etoposide, which is used to treat a number of cancers, including lung cancer, has been in short supply on and off for nearly 2 years. Of the four companies that manufacture it, only one has been able to cite a reason—manufacturing problems.

Typically the intravenous formulation of etoposide is preferred, explained Dr. Ali McBride, a clinical oncology pharmacist at Barnes-Jewish Hospital in St. Louis. Because of the shortage, however, oncologists frequently have been forced to resort to the oral formulation, “and that has led to dosing problems,” Dr. McBride said. Etoposide is also used for patients who undergo hematopoietic stem cell transplants, including children. In several cases, Dr. McBride said, treatments had to be delayed because the drug wasn’t available.

The shortage of two other commonly used chemotherapy agents, doxorubicin and cisplatin, is also emerging “as a real problem,” said Dr. Link. “Doxorubicin is very widely used, so the impact is enormous,” he continued, particularly because for a number of diseases, such as metastatic breast cancer, sarcomas, and lymphomas, doxorubicin is a mainstay of treatment. “Clinical trials have shown it to be a major part of the improvement in outcome,” he said.

With cisplatin, the biggest concern has been in testicular cancer, where its use is directly related to the extremely good survival rates seen with chemotherapy. The alternative, carboplatin, “lowers the cure rate in young men with testicular cancer by 10 to 15 percent,” explained Dr. Lawrence Einhorn of the Indiana University School of Medicine in a recent ASCO interview.

If a drug is in very short supply, it is typically reserved for patients who stand to benefit the most. In most cases, Dr. McBride said, “the priority is patients for whom the therapy is curative.”

The shortage’s impact on medical facilities appears to vary by facility type, noted Bona Benjamin, ASHP’s director of medication-use quality improvement. “Organizations like ambulatory infusion centers that don’t have the usage volume of large hospitals may receive proportionately less drug,” she explained, so some of them are feeling the shortage more acutely than larger medical centers.

Impact on Clinical Trials

Cancer clinical trials are also being affected by the shortage, although the full extent of the impact is unclear. NCI has been advising its clinical trials cooperative groups on how to proceed when a drug that is part of a treatment protocol is in short supply or not available at all.

“The highest priority when shortages occur is to ensure that all patients currently enrolled in the trial are treated appropriately,” explained Dr. Margaret Mooney of NCI’s Division of Cancer Treatment and Diagnosis. Federal regulations allow for trial leaders to deviate from the research protocol to ensure patient safety if there is an immediate hazard, such as when an essential component of the protocol therapy is not available. Those treatment modifications must be documented and communicated to the study patients and the Institutional Review Board (IRB) overseeing the trial, Dr. Mooney said.  

For new patients, she continued, trial sites must work with their local pharmacists to determine if they expect to have an adequate supply of the agents being used in the trial. If they don’t, accrual of new patients is temporarily halted. In cases where a shortage is expected to be prolonged, investigators may amend trial protocols—with IRB review and approval—when there are acceptable alternatives. That is handled on a trial-by-trial basis, Dr. Mooney said.

“It’s not a crisis, but we certainly have felt the effects,” said Dr. Jan Buckner of the Mayo Clinic and chair of the North Central Cancer Treatment Group (NCCTG). The cooperative group hasn’t been forced to stop any of its trials because of the shortage, Dr. Buckner noted, “but we have had to identify alternative regimens that we felt were therapeutically equivalent.”

The shortage has also forced NCCTG to be vigilant about having sufficient drugs on hand at trial sites before enrolling patients in a trial. “We’ve gotten calls from some of our sites asking for assistance with identifying suppliers [or] sharing drugs,” Dr. Buckner continued. “And our local pharmacies and institutions have been working cooperatively to ensure they have enough supplies on hand.”

Although lack of a drug in a study can slow or stop accrual to a clinical trial, Dr. Link said, the “looming problem” could be the analysis of data from trials in which many patients, because of a shortage, had to receive a drug that was not part of the original protocol. At this point, Dr. Mooney stressed, it’s very difficult to say how the shortage will affect the analysis of trials that had to rely heavily on alternative regimens.

Looking forward, said Dr. Link, several common themes and suggested fixes emerged from the November summit on the shortage. Although some will require legislation or regulatory changes, others are more straightforward: “We definitely need to improve communication between the FDA, the drug manufacturers, and the suppliers,” he said.

As the global burden of cancer grows and the market for commonly used cancer drugs expands, Dr. McBride stressed, all of the stakeholders need to remain focused on this issue.

Carmen Phillips

Cancer Research Highlights

Another JAK2 Inhibitor Shows Promise against Myelofibrosis

An experimental drug designed to inhibit growth-promoting signals associated with a mutant form of the Janus-activated kinase 2 (JAK2) protein reduced clinical symptoms and led to durable responses in some patients with myelofibrosis, a disorder in which the bone marrow is replaced by fibrous tissue. The phase I dose-escalation study, published online in the Journal of Clinical Oncology on January 10, evaluated a selective JAK2 inhibitor called TG101348.

Fifty-nine patients were enrolled in the trial, including 28 in the dose-escalation phase. A substantial portion of patients experienced improvements in primary symptoms, including enlargement of the spleen. Myelofibrosis disrupts the production of blood cells, which can lead to severe anemia, weakness, fatigue, and frequently an enlarged spleen and liver.

There are no FDA-approved treatments for myelofibrosis, a debilitating chronic myeloproliferative disorder. The disease can arise independently (primary myelofibrosis) or develop late in the course of two more benign myeloproliferative disorders, essential thrombocythemia or polycythemia vera. Currently, patients with myelofibrosis receive palliative treatment meant to ease the symptoms of the disease.

Although TG101348 was generally well tolerated, the drug caused anemia in some patients, especially at higher doses. A follow-up trial is being planned to see whether adjusting the dose will allow patients to achieve the benefits without the anemia. A second planned trial will test the agent in patients with polycythemia vera.

“The take-home message of this study is that selective anti-JAK2 drugs such as TG101348 should be pursued further in polycythemia vera,” said the lead investigator, Dr. Ayalew Tefferi of the Mayo Clinic. Another message, he continued, is that the scientific community should be aware that the anti-JAK2 drugs tested to date are different from each other, in terms of both their therapeutic activity and their side effects. For example, patients at risk of anemia perhaps should consider drugs that do not have this side effect, he said.

In September 2010, researchers reported positive results from a trial testing an experimental agent known as INCB018424 in patients with advanced myelofibrosis. Unlike TG101348, INCB018424 inhibits JAK1 as well as JAK2. The development of JAK2 inhibitors followed the discovery, in 2005, of an activating mutation in the JAK2 gene in 90 percent of patients with polycythemia vera and 60 percent of patients with primary myelofibrosis or essential thrombocythemia.

An accompanying editorial notes that the development of JAK2 inhibitors “has ushered in a new era of targeted therapies” for myeloproliferative disorders that lack the Philadelphia chromosome. Patients usually see improvements in their symptoms within a month of starting therapy, and this improvement appears to be durable, wrote Dr. Srdan Verstovsek of the University of Texas M. D. Anderson Cancer Center. The drugs do not eradicate the malignant clone, however, and more research is needed to learn how best to use them, he added.

Treatment for Ductal Carcinoma In Situ Varies Substantially

Treatment for ductal carcinoma in situ (DCIS), a noninvasive condition that may progress to invasive breast cancer, varies substantially between surgeons, and this variation can affect the likelihood of disease recurrence, researchers reported online January 3 in the Journal of the National Cancer Institute.

The researchers, led by Dr. Andrew Dick from the nonprofit RAND Corporation, studied medical records from 994 women with DCIS who were treated in either Monroe County, NY, or at the Henry Ford Health System in Detroit. They collected data on disease characteristics, such as tumor size and the width of the surgical margins (i.e., the closeness of cancer cells to the edge of the excised tissue); treatments, including surgery, radiation therapy, and tamoxifen; and outcomes, primarily recurrence in the same breast.

Almost all women had breast-conserving surgery (BCS) as a first procedure, but more than half required at least one additional surgery—BCS or mastectomy—to remove residual cancer cells. Only 60 percent of women who had BCS as their final surgery received radiation therapy, despite evidence from clinical trials showing that adjuvant radiation therapy reduces disease recurrence.

The authors found that recurrence rates were lowest for women who had a mastectomy, highest for women who had BCS without radiation therapy, and intermediate for those who had BCS followed by radiation therapy. Women who had positive or close surgical margins after their last surgery were also more likely to have a recurrence than women whose surgical margins were free of cancer cells.

The authors also found that treatments and surgical margin width varied widely among surgeons, leading to large variations in recurrence risk. The authors estimated that increasing surgeons' rates of radiation therapy use and decreasing the rates of positive or close margins could reduce 5- and 10-year recurrence rates by 15 to 30 percent.

The study could not determine whether these results were influenced by women’s potential preference for surgeons who are known for recommending less invasive treatment, by variation in decision making among surgeons, or by a lack of communication over the risks and benefits of each procedure. However, “because of the importance of treatment choice and margin status in predicting outcomes, these unexplained differences by surgeons could have profound implications for health outcomes,” the authors concluded.

Major Gene Mutation Identified in Lymphoma Tumors

Researchers have identified a recurring genetic mutation that drives the growth of some lymphoma tumors by activating multiple signaling pathways associated with cancer. The mutation, in a gene called MYD88, was found in nearly a third of patients with the activated B-cell-like (ABC) subtype of diffuse large B-cell lymphoma (DLBCL), which is the least curable form of DLBCL. Further experiments pointed to possible treatment strategies, Dr. Louis Staudt of NCI’s Center for Cancer Research and his colleagues reported December 22 in Nature.

The MYD88 protein normally plays a role in the body’s immune response. But the researchers found that the mutant form of MYD88, known as L265P, spontaneously assembles a protein complex that promotes the survival of lymphoma cells through the NF-κB and JAK-STAT3 signaling pathways. Twenty-nine percent of the 155 ABC DLBCL samples examined had the same MYD88 mutation, and the change was rare or absent in other kinds of DLBCL and other lymphomas. 

The researchers also found that blocking a component of the protein complex assembled by the L265P form of MYD88—a protein called IRAK4—caused lymphoma cells with the MYD88 mutation to die. Pharmaceutical companies are developing IRAK4 inhibitors to treat inflammatory and autoimmune diseases, and these agents could be tested in lymphoma, the researchers said.

To make the discovery, the researchers first identified genes that are required for the survival of ABC DLBCL (through a technique known as RNA interference). After identifying MYD88 and IRAK1 (a gene related to IRAK4) as essential genes, the researchers sequenced the genes in patient samples and found the recurring MYD88 mutation. The next step was to understand how the MYD88 mutation contributes to cancer.

“A major part of the story for DLBCL has now been solved,” said Dr. Staudt, noting that the MYD88 mutation is the most common mutation found in DLBCL to date. In effect, lymphoma cells “hijack” an immune regulator pathway for their malignant purposes, he continued. MYD88 may be frequently mutated, he speculated, because the mutation controls two major signaling pathways in cancer and “cancer cells like to get the most bang for their buck.”

A Conversation With

A Conversation with Dr. Barry Kramer about Cancer Screening

The editor-in-chief of NCI's Physician Data Query (PDQ) Screening and Prevention Editorial Board talks about the types of effective cancer screening tests available and the risks that are sometimes associated with cancer screening.

You must have flash installed and enabled to view the video.


Video produced and edited by Daniel Marmorstein and Sarah Curry

Spotlight

Survivorship
This article is in a series of stories related to cancer survivorship. Look for the symbol on the left in an upcoming issue for the next article in the series.

Preserving Fertility While Battling Cancer

Dr. Neeraj Arora and his daughter Shairee, who was conceived after he was treated for non-Hodgkin lymphoma. When Dr. Neeraj Arora was treated for non-Hodgkin lymphoma in his 20s, his doctors never mentioned that the treatment could leave him infertile. Fortunately it didn’t; his daughter Shairee turns 6 years old next month.

Dr. Neeraj Arora was a 25-year-old graduate student when he was diagnosed with non-Hodgkin lymphoma (NHL). His oncologist recommended aggressive chemotherapy and radiation, beginning immediately, to stem the rapid growth of the cancer.

One day, waiting in the doctor’s office for his next round of chemotherapy, he happened to pick up a booklet about NHL treatment. Infertility, he read, was a common side effect of the regimen he was receiving.

“My doctors somehow forgot to mention that,” Dr. Arora recalled. Single at the time, he hadn’t given a lot of thought to becoming a father, but it upset him that no one had considered the risk to his fertility worth mentioning.

It was 1994, and the ability to have children after cancer treatment wasn’t even a blip on the radar screen for oncologists who were considering risks they should discuss with their patients. The concept of cancer survivorship—of a life beyond cancer—was still in its infancy.

Guidelines for Conversation

The estimated number of cancer survivors of reproductive age in the United States is now approaching half a million. Although cancer treatments have evolved to cause fewer harmful side effects in these patients, radiation therapy and many chemotherapy agents can still damage fertility. (View a table with more details.)

The most frequent cause of impaired fertility in male cancer survivors is chemotherapy- or radiation-induced damage to sperm. The fertility of female survivors may be impaired by any treatment that damages immature eggs, affects the body’s hormonal balance, or injures the reproductive organs.

You must have flash installed and enabled to view the video.


Video produced and edited by Sarah Curry

In 2006 the American Society of Clinical Oncology published guidelines recommending that oncologists discuss with all patients of reproductive age the possibility of treatment-related infertility, as well as options for preserving fertility, and provide them with referrals to reproductive specialists. Recent surveys, however, have found that fewer than half of oncologists in the United States are following these guidelines and that even oncologists who regularly discuss the risk of infertility with patients rarely refer them to reproductive specialists.

The potential impact of cancer treatment on fertility “has not been at the forefront of what oncologists think they need to discuss with patients and families up front,” said Dr. Peter H. Shaw, who directs the Adolescent and Young Adult Oncology Program at Children’s Hospital of Pittsburgh. “But it needs to be discussed right off the bat, once you have the diagnosis.”

Elissa Bantug was 23 years old when she was diagnosed with breast cancer in 2005. She had one child already and wanted a larger family. The doctors who she consulted dismissed her questions about the likely effects of treatment on her fertility. “One oncologist said to me, ‘Elissa, do you want to have kids or do you want to live? Because that’s what we’re dealing with,’” she recalled.

Bantug’s experience echoes survey findings that suggest oncologists may place a lower value than patients do on the risk of future infertility. In such surveys, many oncologists say they feel ill informed about fertility preservation and worry that discussing it will place an added burden on patients who are already stressed because of their cancer diagnosis.

But studies suggest that cancer patients are very concerned about risks to their fertility and want to know how these risks can be mitigated.

“To ensure quality of survivorship, informed dialogues about patients’ concerns and desires for their future need to be part of the initial treatment planning process,” said Dr. Julia Rowland, director of NCI’s Office of Cancer Survivorship. Moreover, she noted, if discussions about fertility do not happen until after cancer treatment has been completed, it “is generally too late to preserve reproductive options.”

Researching Options

Resources on Fertility Preservation for Cancer Survivors

Oncofertility Consortium
NIH-supported interdisciplinary research consortium exploring relationships between health, disease, survivorship, and fertility preservation in young cancer patients
 
MyOncofertility.org
Patient education resource provided by the Oncofertility Consortium
 
Fertile Hope
Nonprofit organization affiliated with the Lance Armstrong Foundation that provides information and support to cancer patients and survivors at risk for infertility

American Society of Clinical Oncology
Recommendations on fertility preservation in people treated for cancer

Options for preserving cancer patients’ ability to have biological children depend on many factors, including the patient’s sex, age, type of cancer, and type of treatment. Most procedures remain experimental. Only two are well established and known to be effective: for men, freezing and banking sperm; for women, freezing and banking embryos.

Most options, whether established or experimental, are costly and unlikely to be covered by health insurance. And most of these options must be undertaken before or during cancer treatment. Patients who have just received a cancer diagnosis usually have a very brief window of time in which to decide whether to pursue fertility preservation—and, if so, to determine which procedure is most appropriate for their circumstances.

To help patients navigate the maze of fertility preservation options, NCI-supported researchers are developing Web-based decision aids that educate patients about cancer’s effects on fertility, explain the pros and cons of different fertility-preservation procedures, and help them clarify their values so that they can reach a decision they are comfortable with.

“It’s a complicated decision,” said Dr. Christine M. Duffy of Brown University and Rhode Island Hospital in Providence, who is developing a fertility preservation decision aid for women with breast cancer. “Often there is no obvious best choice. It depends on your values, on how important it is for you to have children, on how much you’re willing to go through.”

These factors are incorporated in a decision-aid tool on sperm banking that Dr. Leslie R. Schover of the University of Texas M. D. Anderson Cancer Center in Houston has pilot tested. The decision aid is part of a comprehensive educational tool about sperm banking for patients, families, and health care professionals.

Through a series of questions, patients are encouraged to think about things they may never have considered, Dr. Schover explained, such as whether they would feel sad if they never had a child or whether their family would accept a child born from donor insemination. In pilot testing, patients who used the decision aid were less conflicted about the decisions they made on sperm banking than patients who did not use it.

Against the Odds

Patrick McArthur can attest to the benefits of an informed, carefully considered decision about fertility in the wake of cancer. Diagnosed with locally advanced lymphoblastic lymphoma (a type of NHL) in 2005 when he was 25 years old, he was counseled by a nurse about the possible effects of his treatment on fertility and about the option of freezing and banking sperm. “I knew immediately that I wanted that insurance policy,” he said.

Health Outcomes in Children of Cancer Survivors

Cancer survivors may have a strong desire for children, but they may worry that their cancer treatment could lead to health problems, such as birth defects or genetic abnormalities, for their offspring.

Research findings to date suggest, however, that although infants born to survivors of childhood cancer may be at higher risk for premature birth and low birth weight, they are no more likely than other children to suffer from birth defects, genetic disorders, or chromosomal abnormalities.

An attorney in San Antonio, TX, McArthur is now the father of a baby girl, who was conceived naturally and born in June 2010. “My wife and I decided to try for a natural conception, knowing that if it didn’t happen we had the banked sperm as a backup,” he said.

Four years after her initial breast cancer diagnosis (and following treatment for a recurrence in 2007), Elissa Bantug and her husband consulted fertility specialists to see if it would be possible for her to get pregnant. “They warned me that it would be very difficult,” she recalled. But against the odds, she conceived right away. Her baby daughter turned 1 in October 2010. Bantug is now project coordinator of the Breast Cancer Survivorship Program at Johns Hopkins Sidney Kimmel Comprehensive Cancer Center in Baltimore.

Dr. Arora, now a program director in NCI’s Division of Cancer Control and Population Sciences, is the father of a little girl who will turn 6 next month. “Given what I now know about the toxicity of the intense chemotherapy I received,” he said, “I consider the birth of my daughter to be a miracle.”

To help address some of the issues related to fertility preservation decisions and other areas relevant to young survivors, NCI, with support from the Lance Armstrong Foundation, has sponsored the Adolescent and Young Adult Health Outcomes and Patient Experience (AYA HOPE) Study. Data are forthcoming from this population-based cohort of young survivors identified through SEER cancer registries.

Eleanor Mayfield

New Options for Preserving Fertility in Children

Children who are diagnosed with cancer before they reach puberty now have extremely good odds of surviving their cancer. But the treatments that save their lives may destroy their ability to have their own children. Currently no standard fertility preservation options exist for these children.

Adolescent boys and young men can opt to have their semen frozen and preserved in a sperm bank. Younger boys, however, do not yet produce sperm, although their testicular tissue contains immature cells that will eventually produce sperm.

Prepubescent girls’ ovaries contain immature eggs, or follicles, that are not yet capable of being fertilized, so egg freezing—a rapidly developing but still experimental fertility preservation option for adolescent girls and young women—isn’t feasible for younger girls.

Researchers at the Children’s Hospital of Philadelphia, led by Dr. Jill Ginsberg, are studying testicular tissue banking as a fertility preservation option for prepubescent boys. A biopsy is performed to remove a small piece of one testicle. Half of the specimen is frozen for possible future use by the patient. The other half is sent to the lab of Dr. Ralph Brinster at the University of Pennsylvania School of Veterinary Medicine, who has successfully developed a method of growing sperm stem cells in culture, reimplanting them, and restoring fertility in male rats. Dr. Brinster is now attempting to apply this technology to human sperm stem cells.

Biopsies have been performed on 23 boys so far, said Dr. Ginsberg. “In most cases, the parents of prepubescent boys are willing to agree to the procedure and are grateful for the opportunity,” she said, “even though there is no certainty that the preserved tissue will be useful to their sons in the future.”

Nine centers participating in the NIH-funded Oncofertility Consortium are offering ovarian tissue banking to prepubescent girls in an experimental protocol. One of the patients’ ovaries, or a section of one ovary, is removed. As in the testicular tissue banking study, most of the specimen is frozen for the patient’s possible future use, while a portion is used for research on optimizing techniques for freezing and thawing ovarian tissue for use in transplantation or in vitro follicle maturation.

“Although it is still at an experimental stage, in vitro follicle maturation may provide an important new option for preserving fertility in young women and girls with cancer,” said Dr. Teresa Woodruff, director of the Oncofertility Consortium.

Featured Clinical Trial

Comparing First-Line Therapies for Mucinous Ovarian or Fallopian Tube Cancer

Name of the Trial
Phase III Study of Carboplatin and Paclitaxel with Versus without Bevacizumab Compared to Oxaliplatin and Capecitabine with Versus without Bevacizumab as First-Line Therapy in Patients with Newly Diagnosed Stage II-IV or Recurrent Stage I Mucinous Epithelial Ovarian or Fallopian Tube Cancer (GOG-0241).  See the protocol summary.

Dr. David Gershenson Dr. David Gershenson

Principal Investigators
Dr. David Gershenson and Dr. Richard Penson, Gynecologic Oncology Group (GOG)

Why This Trial Is Important
Mucinous ovarian cancer is a rare type of ovarian epithelial cancer, representing less than 5 percent of the roughly 21,000 cases of ovarian cancer diagnosed each year in the United States. This type of ovarian cancer tends to be detected earlier than the more common serous type of ovarian epithelial cancer, leading to a generally favorable prognosis. However, women with more advanced mucinous ovarian tumors typically fare worse than those with more advanced serous ovarian tumors. Researchers believe one possible explanation for this discrepancy is that mucinous ovarian cancer is biologically different from the serous type and is more similar to cancers of the gastrointestinal (GI) tract, such as colorectal or appendiceal cancers.  

Because of the similarities between primary mucinous ovarian tumors and GI cancers, GOG researchers want to know if using combination chemotherapy with the drugs capecitabine and oxaliplatin, which is standard for advanced colorectal cancer, will improve the overall survival of women with advanced mucinous ovarian cancer compared with the current standard chemotherapy combination used for ovarian epithelial cancer, carboplatin plus paclitaxel. They also want to know if adding the antibody bevacizumab to either regimen will benefit patients. Bevacizumab has been shown to improve outcomes in colorectal cancer when added to capecitabine/oxaliplatin and in ovarian epithelial cancer in general when added to paclitaxel/carboplatin.

In this trial, which is being conducted in both the United States and the United Kingdom, women with stage II to IV or recurrent stage I mucinous epithelial ovarian or fallopian tube cancer will be randomly assigned to receive either paclitaxel/carboplatin with or without bevacizumab or oxaliplatin/capecitabine with or without bevacizumab. In addition to looking for differences in overall survival, doctors will monitor the patients in the four treatment groups for differences in progression-free survival, tumor response rates, drug toxicity, and quality of life.  

“The GOG Rare Tumor Committee, which guided the development of this study in the United States, is really focused on trying to develop better therapies for rare ovarian tumors because we don’t believe they should be lumped in with the more common high-grade serous ovarian cancers,” said Dr. Gershenson. “The purpose of this study is to try to identify a more effective and active treatment against mucinous carcinoma of the ovary.

 “We really know a lot less about the molecular biology of mucinous ovarian tumors than we do about other rare ovarian tumors,” Dr. Gershenson added. “So another important aspect of this study is the collection of tissue for a tissue repository that we can use in the future to perform studies to learn more about the biology and genetics of mucinous carcinoma of the ovaries.”

For More Information
See the lists of entry criteria and trial contact information or call the NCI's Cancer Information Service at 1-800-4-CANCER (1-800-422-6237). The toll-free call is confidential.

An archive of "Featured Clinical Trial" columns is available at http://www.cancer.gov/clinicaltrials/ft-all-featured-trials.

Cancer Center Profile

The Kimmel Cancer Center at Thomas Jefferson University

Director: Dr. Richard Pestell • 233 S. 10th Street, Philadelphia, PA 19107
Phone: 1-888-955-1212 • Web site: http://www.kimmelcancercenter.org

Background

The Kimmel Cancer Center at Thomas Jefferson University The Kimmel Cancer Center at Thomas Jefferson University

The Kimmel Cancer Center (KCC) at Thomas Jefferson University, in Philadelphia, was founded in 1991 and became an NCI-designated Cancer Center in 1996. It conducts oncology research and supports patient care, education, and health information services for Thomas Jefferson University, Thomas Jefferson University Hospital, Methodist Hospital, and the Kimmel Cancer Center Network, which includes 22 hospital and practice partners and provides services to more than 12,000 newly diagnosed cancer patients each year.

Research

The KCC’s mission is to make transformational cellular and molecular biology discoveries about the malignancy process and the individual’s response to it; effectively translate the latest research discoveries into clinical trials to provide the highest quality of care to all patients, including those from diverse ethnic and racial populations; and to provide expert and humanitarian care to cancer patients, their families, and those at risk for getting the disease.

The KCC comprises seven research programs that support this mission, four focused on basic and translational science (Cancer Cell Biology & Signaling, Molecular Biology & Genetics, Immunological Mechanisms in Cancer, and Endocrine Mechanisms & Hormone Action in Cancer), two that concentrate on translational and clinical components of cancer care (Radiation Research & Translational Biology and Gastrointestinal Cancer), and one evolving program that focuses on population studies. Along with the Kimmel Cancer Center Network partners, the KCC offers patients access to more than 100 active clinical trials.

The KCC is dedicated to producing a new generation of talented scientists and participates in four NIH/NCI training grants for graduate students and post-doctoral fellows. Of the more than 120 Ph.D. candidates enrolled in the College of Graduate Studies at Thomas Jefferson University, approximately 81 are working with KCC mentors. Also, a large proportion of the 160 post-doctoral fellows on campus are involved in KCC research programs.

Patient Care

The internationally renowned clinical teams at the KCC treat virtually every type of cancer, with multidisciplinary centers that focus on brain tumors, breast cancer, colon and rectal cancers, gynecologic tumors, liver cancer, lung cancer, pancreatic cancer and related diseases, and urologic cancers. The KCC has also recently opened a new consultative service focused on treating senior adults who have cancer. The affiliated Thomas Jefferson University Hospital has been recognized by Blue Cross & Blue Shield as a Blue Distinction Center for Complex and Rare Cancers for offering the best practices and standards of cancer care.

The KCC also offers a variety of support groups and programs for patients, such as Back In The Saddle, a program to help patients transition back from treatment to normal life; the Buddy Program, where patients are paired with a partner who understands what it’s like to be diagnosed with cancer; the Caregiver Connection, a support group for people who take care of someone going through cancer treatment; and Coffee and Conversation, a group that allows young adults to talk about things like treatment side effects, relationships, and employment.

Notes

NCI Director Announces New Senior Staff Member

John Czajkowski John Czajkowski

Dr. Harold Varmus recently announced the appointment of new staff leadership in the NCI Office of the Director. John Czajkowski will fill the post of deputy director for management. Czajkowski comes to NCI from the U.S. Department of the Treasury’s Office of the Inspector General, where he served as director of the Office of Management, a position that included responsibilities as chief financial officer and chief information officer, as well as management of personnel, acquisitions, space, and security.

Prior to his time at the Department of the Treasury, Czajkowski held senior positions in the U.S. Office of Personnel Management from 2003 to 2008. He also served for 8 years at NIH, including senior management positions in the Office of the Director, Center for Scientific Review, and Center for Information Technology. Since 2007, Czajkowski has held an adjunct faculty position at American University’s School of Public Affairs. Czajkowski has a degree in economics from the University of Maryland, Baltimore County and a Masters of Public Administration from American University.

Recap of Last Month’s President's Cancer Panel Meeting

The President’s Cancer Panel held the third meeting of its 2010–2011 series, The Future of Cancer Research: Accelerating Scientific Innovation, on December 14 in Bethesda, MD. The meeting included expert testimony and discussion about opportunities to accelerate progress within the National Cancer Program (NCP), particularly through the Internet and other technologies. NCI Director Dr. Harold Varmus was one of the speakers at the meeting.

Participants highlighted emerging models of clinical research that are revolutionizing the ways in which research projects are planned and carried out. Many organizations are using Internet-based and other technologies to engage patients in clinical research, for example, given the widespread and increasing access to broadband Internet and wireless mobile devices, which allow people to manage and share health information more easily.

Panelists noted that these technologies undoubtedly have the potential to support public health advances, but that they are not likely to improve health outcomes directly. Health professionals still play an essential role in communicating information to patients and supporting patient decision-making, they explained.

The panelists also stressed that efforts to promote team science through multi-institutional and cross-disciplinary collaborations are vital in supporting transformative cancer research. However, such far-reaching collaborations have logistical challenges.

Meeting participants emphasized the need for improved coordination within the NCP to maximize its efficiency and to enhance data and information sharing across institutions and with the public. “The scientific community needs to embrace the idea of making our knowledge fully accessible to everyone—the public and everybody else,” Dr. Varmus said.

The Panel will summarize findings and recommendations from this meeting, along with the other meetings in the series, in its 2010–2011 Annual Report to the President of the United States.

In Memoriam: Susan Lowell Butler

Susan Lowell Butler, the executive director of the D.C. Cancer Consortium, who was featured in a recent Bulletin article and a related video about ovarian cancer, died on December 18 at her home in Alexandria, VA. She was 66 years old.

Ms. Butler was first diagnosed with ovarian and breast cancer in 1995. She was successfully treated and in remission for 13 years. After her diagnosis, she helped found the Ovarian Cancer National Alliance, an advocacy and support group for women who have ovarian cancer. Ms. Butler also served on the Director’s Consumer Liaison Group for NCI and on the advisory committee of the NIH Clinical Center.

Ms. Butler was an avid supporter of clinical trials to improve treatment options for cancer patients. “It’s a very different world today for patients undergoing cancer treatment,” she said, reflecting on her cancer experience in the 1990s and her recent recurrence. “Nope, we don’t have a cure. But we have quality of life in a way that we sure didn’t back then.”

250 Issues and Counting!

With this issue, NCI’s award-winning online newsletter, the NCI Cancer Bulletin, has published 250 issues since its launch in January 2004.

Each year, Federal and contract staff in NCI’s Office of Communications and Education produce 24 issues of the Bulletin. More than 50,000 researchers, clinicians, cancer survivors, advocates, and other health professionals from around the world subscribe, and others follow our coverage through our RSS and Twitter feeds.  

For a look back at some of our coverage of news and events for each 50 issues, click the following links: