National Cancer Institute NCI Cancer Bulletin: A Trusted Source for Cancer Research News
December 11, 2012 • Volume 9 / Number 24

NEWS

Ten Years of Tamoxifen Leads to Fewer Breast Cancer Recurrences, Improves Survival SABCS

Photo of people attending the 2012 San Antonio Breast Cancer Symposium (Photo by Todd Buchanan ©2012)

For some women with breast cancer, taking tamoxifen for 10 years after primary treatment (adjuvant therapy) leads to a greater reduction in breast cancer recurrences and deaths than taking the drug for only 5 years, according to the results of a large international clinical trial.

The findings from the ATLAS trial—presented at the San Antonio Breast Cancer Symposium (SABCS) and published in The Lancet on December 5—are likely to change clinical practice, several researchers said. Read more >>

A MESSAGE TO READERS

NCI Cancer Bulletin Publication Break

The NCI Cancer Bulletin will not be published on December 25. Our next issue will be published on January 8, when we resume our usual biweekly publication schedule. 

To find stories from past issues, please visit our archive/search page.To suggest a cancer research topic that you would like to see covered in the coming year, send us your feedback here.

IN DEPTH

UPDATES

  • FDA Update

    • Abiraterone Approval Extended to Treat Late-Stage Prostate Cancer
    • Cabozantinib Approved to Treat Rare Type of Thyroid Cancer
  • Notes

    • New National Cancer Advisory Board Members Named
    • NCI Recognizes 12 Clinical Investigators with Leadership Awards
    • National Cancer Advisory Board Discusses NCI Funding Patterns, Program Updates
    • NCI FY2013 Budget Proposal Published Online
    • NCI E-Books Available on Mobile Website
    • Annual Report on NCI Disparities Research Released


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

Ten Years of Tamoxifen Reduces Breast Cancer Recurrences, Improves Survival

Photo of people attending the 2012 San Antonio Breast Cancer Symposium (Photo by Todd Buchanan ©2012)More than 7,500 people from more than 90 countries attended the 2012 San Antonio Breast Cancer Symposium, where findings from the ATLAS trial were presented. (Photo by Todd Buchanan ©2012)

For some women with breast cancer, taking adjuvant tamoxifen (Nolvadex) for 10 years after primary treatment leads to a greater reduction in breast cancer recurrences and deaths than taking the drug for only 5 years, according to the results of a large international clinical trial.

The findings from the ATLAS trial—presented at the San Antonio Breast Cancer Symposium (SABCS) and published in The Lancet on December 5—are likely to change clinical practice, several researchers said.

Nearly 7,000 women with early-stage, estrogen receptor-positive breast cancer were enrolled in the trial between 1996 and 2005. After taking tamoxifen for 5 years, participants were randomly assigned to continue taking tamoxifen for another 5 years or to stop taking it.

From 5 to 9 years after the women began tamoxifen therapy, there was little difference in outcomes between the two treatment groups. This finding is consistent with those from other trials of adjuvant tamoxifen therapy, which showed that 5 years of tamoxifen can substantially reduce the risk of the cancer returning and of cancer death in the next few years, what one of the trial investigators, Dr. Richard Gray of Oxford University, UK, called a "carryover effect."

The improved outcomes with longer tamoxifen use emerged only after the 10-year mark, Dr. Gray explained during an SABCS press briefing. Among the women who took tamoxifen for 10 years, the risk of breast cancer returning between 10 and 14 years after starting tamoxifen was 25 percent lower than it was among women who took it for 5 years, and the risk of dying from breast cancer was nearly 30 percent lower.

Overall, from 5 to 14 years after participants began tamoxifen treatment, the risk of the cancer returning and the risk of dying from breast cancer was lower in women who took tamoxifen for 10 years, compared with those who took it for 5 years. (See the table.)

Breast Cancer Recurrence and Death 5 to 14 Years after Beginning 
5 or 10 Years of Adjuvant Tamoxifen

 5 Years10 Years
Risk of Recurrence25.1 percent21.4 percent
Risk of Death from Breast Cancer15.0 percent12.2 percent

Tamoxifen can have side effects, including hot flashes, fatigue, and an increased risk of blood clots and endometrial cancer. But there was no substantial increase in serious side effects, including endometrial cancer incidence or death, in women who took tamoxifen for the longer period, Dr. Gray reported. The absolute increased risk of death from endometrial cancer in women who took tamoxifen for 10 years versus 5 years was 0.2 percent.

The risk-benefit ratio of any treatment must always be seriously considered, he stressed. But, in the case of extended tamoxifen treatment, he argued, the "risks are far smaller than the benefits."

At least one other trial of extended tamoxifen therapy reached the opposite conclusion to the ATLAS trial. This much smaller trial (about 1,200 patients) conducted in the United States by the National Surgical Adjuvant Breast and Bowel Project (NSABP), ran from the early 1980s to the mid-1990s. It found that continuing adjuvant treatment with tamoxifen beyond 5 years did not decrease breast cancer recurrences or deaths.

Why the trials had different findings is unclear. However, with its larger size and longer follow-up, the ATLAS results are more definitive, noted several researchers.

The ATLAS results will have "a major, immediate impact on premenopausal women" with early-stage, estrogen receptor-positive breast cancer, said Dr. Peter Ravdin of the University of Texas Health Sciences Center at San Antonio, who moderated the press briefing.

Among the women who took tamoxifen for 10 years, the risk of breast cancer returning between 10 and 14 years after starting tamoxifen was 25 percent lower than it was among women who took it for 5 years, and the risk of dying from breast cancer was nearly 30 percent lower.

That patient population represents a substantial number of women diagnosed with breast cancer in the United States each year, approximately 30,000 to 35,000 women. Postmenopausal women with early-stage, estrogen receptor-positive breast cancer are often treated with aromatase inhibitors after tamoxifen. However, aromatase inhibitors are not effective in premenopausal women, Dr. Ravdin explained, so tamoxifen is the standard of care in these patients.

"We can now tell [premenopausal patients] that clinical evidence shows that 10 years [of tamoxifen] is superior to 5 years," Dr. Ravdin said. "And I'm going to be comfortable doing that."

But the decision to use tamoxifen for the extended period is by no means clear cut, he stressed.

Women with a higher risk of their cancer returning long after adjuvant therapy ends, such as those whose cancers had infiltrated their lymph nodes or who had larger tumors, "will definitely be strong candidates for continuation of [tamoxifen] therapy," he said. But a woman at low risk of recurrence at any point "may very well rationally decide she doesn't want to take tamoxifen beyond 5 years," he added.

The findings may have implications for postmenopausal women as well, said Dr. Claudine Isaacs, co-director of the breast cancer program at Georgetown Lombardi Comprehensive Cancer Center.

Postmenopausal women are often prescribed 5 years of adjuvant therapy with an aromatase inhibitor. (Some women, however, receive tamoxifen followed by an aromatase inhibitor over a 5-year period.) But, Dr. Isaacs noted, a fair number of women can't tolerate aromatase inhibitors because of their side effects, so the ATLAS results may lead some clinicians and their postmenopausal patients to consider whether an extended duration of adjuvant tamoxifen may be appropriate.

Even for postmenopausal women who can tolerate aromatase inhibitors, the ATLAS findings raise other questions, observed Dr. Trevor Powles of the Cancer Center London in an accompanying editorial in The Lancet.

"No data are available to suggest that [the aromatase inhibitor] letrozole for 5 years is better for long-term benefit than 10 years of tamoxifen, which has a proven effect in terms of long-term risk reduction of relapse and mortality," Dr. Powles wrote.

In a post on her "Chemobrain" blog, breast cancer survivor and cancer advocate AnneMarie Ciccarella urged women who are candidates for adjuvant tamoxifen, regardless of their menopausal status, to carefully consider their options. "Sit down with your doctor. Ask questions. Understand how this study impacts your own set of circumstances," she wrote. "Remember, there is no cookie cutter answer."

Carmen Phillips

Further reading: "In Breast Cancer, Moving Toward More Personalized Hormone Therapies"

Cancer Research Highlights

Chemotherapy after Surgery Improves Survival When Some Breast Cancers Return

Among women whose breast cancer has recurred but not spread beyond nearby tissues, those who received chemotherapy after surgery had better disease-free and overall survival, a new study shows. Patients with estrogen receptor (ER)-negative tumors appeared to derive the greatest benefit. The results, from the CALOR trial, were presented December 6 at the San Antonio Breast Cancer Symposium.

"This is the first randomized controlled study that shows that adjuvant chemotherapy works in these patients," Dr. Stefan Aebi, head of the division of medical oncology at Luzerner Kantonsspital in Lucerne, Switzerland, and CALOR co-chair, said in a press release.

Dr. Aebi and his colleagues randomly assigned 162 women who had a local or regional recurrence following prior breast-conserving surgery or a mastectomy to receive adjuvant chemotherapy or not (85 and 77 women, respectively). The trial organizers recommended the use of combination chemotherapy and treatment for 3 to 6 months, but the choice of chemotherapy regimen was left to the discretion of patients' physicians. Treating physicians could also give patients radiation therapy, hormone therapy, or anti-HER2 therapy as appropriate.

Although the trial accrued fewer patients than planned, statistically significant differences were observed. After a median of 5 years of follow-up, the risk of recurrence was 41 percent lower in women treated with chemotherapy than in women who did not receive chemotherapy. And the overall survival rate was higher among patients who received chemotherapy than among those who did not, leading to a 59 percent reduction in the risk of death. (See the table.)

Rate of Disease-Free and Overall Survival, with and without Chemotherapy

 

With 
Chemotherapy

Without 
Chemotherapy

P Value
(0.05 and smaller are statistically significant)

Disease-Free Survival at 5 Years

ER negative

ER positive

69 percent

67 percent

70 percent

57 percent

35 percent

69 percent

0.0455

0.007

0.87

Overall Survival at 5 Years

ER negative

ER positive

88 percent

79 percent

94 percent

76 percent

69 percent

80 percent

0.02

0.12

0.12

When stratified by tumor type, there was a striking difference in the disease-free survival rate between women with ER-negative tumors who received chemotherapy and those who did not. Women with ER-positive tumors received appropriate hormonal therapy, and there were very few recurrences in that group, regardless of whether they received chemotherapy. Therefore, the majority of benefit was seen in women with ER-negative tumors.

These results show a "dramatic improvement in ER-negative [disease] using common chemotherapy drugs," said Dr. Jo Anne Zujewski, head of Breast Cancer Therapeutics in NCI's Division of Cancer Treatment and Diagnosis, who was not involved in the study. "[This] will be practice changing for a small subset of patients."

This trial was funded in part by NCI (U10-CA-37377, U10-CA-69974, U10-CA-12027, U10-CA-69651, and CA-75362). 

New Targeted Treatment May Slow Disease in Patients with Advanced GIST

A new oral drug, regorafenib (Stivarga), may delay the progression of advanced gastrointestinal stromal tumors (GIST) that are resistant to treatment. Results from an international clinical trial published November 22 in The Lancet demonstrated that patients treated with regorafenib lived longer without their disease progressing than patients who received a placebo.

GIST is a relatively rare cancer that is driven, in most cases, by mutations that activate the KIT or PDGFRA kinase signaling pathways. Because this type of GIST is resistant to standard chemotherapy, most tumors are surgically removed if the disease has not spread.

The tyrosine kinase inhibitor imatinib (Gleevec) was the first drug approved for inoperable GIST. However, most GIST tumors develop resistance to imatinib after about 2 years of treatment. Patients with imatinib-resistant tumors are then treated with sunitinib (Sutent), but the disease usually develops resistance to sunitinib and progresses within 1 year. Patients with advanced GIST that is resistant to both imatinib and sunitinib have no other standard treatment options.

Based on results from an earlier phase II trial, Dr. George D. Demetri of the Dana-Farber Cancer Institute and his colleagues compared regorafenib with placebo in patients with metastatic or inoperable GIST who had been treated previously with imatinib and sunitinib. Regorafenib, which inhibits multiple kinases, was approved in September for metastatic colorectal cancer.

The randomized, placebo-controlled phase III trial included 199 patients with advanced GIST, of whom 133 were randomly assigned to receive regorafenib and 66 to receive a placebo. Those who received regorafenib lived without their cancer progressing for a median of 4.8 months, compared with 0.9 months among patients who received a placebo. There was no difference in overall survival between the patients who initially received regorafenib and those who received the placebo. The authors suggested, however, that this could have been due to crossover: 85 percent of patients assigned to receive the placebo crossed over to receive regorafenib after their disease progressed.

All patients who received regorafenib experienced side effects. Just over 60 percent reported a severe drug-related adverse event, compared with 14 percent of patients who received the placebo.

"The case for routine use of this drug in patients who have failed imatinib and sunitinib is strong," the authors of an accompanying editorial wrote. Dr. Demetri said, "It's encouraging to have developed this third targeted drug to manage a disease that was uniformly untreatable before 2000."

The maker of the drug, Bayer Healthcare Pharmaceuticals, has filed for Food and Drug Administration approval of regorafenib to treat GIST.

This trial was funded in part by Bayer HealthCare Pharmaceuticals and NCI (Gastrointestinal Cancer SPORE Grant 1P50CA127003-05).

Study Explores Why Double Mastectomy Rate Is on the Rise

New results from a population-based study show that about 75 percent of women diagnosed with cancer in one breast who chose to have a double mastectomy did so despite being at low risk of developing a new cancer in the unaffected (contralateral) breast. Greater degree of worry about cancer recurrence was associated with removing the breast not affected by cancer, known as contralateral prophylactic mastectomy (CPM).

Dr. Sarah Hawley of the University of Michigan presented the findings, from a patient survey and analysis of SEER cancer registry data, November 30 at the American Society of Clinical Oncology's (ASCO) Quality Care Symposium in San Diego.

Only a small percentage of women diagnosed with breast cancer have clinical risk factors known to increase their chances of developing a new cancer in the unaffected breast—that is, mutations in the BRCA1 or BRCA2 genes and/or a strong family history of breast or ovarian cancer. Yet several studies, including a previous analysis of SEER data, show that rates of CPM among U.S. women with breast cancer are rising.

To investigate why women may choose CPM, Dr. Hawley and her colleagues surveyed roughly 1,500 ethnically and racially diverse women diagnosed with breast cancer that had been reported to the Detroit and Los Angeles SEER registries. Of the 564 women who received mastectomies, 107 had CPM. The remaining women had breast conserving surgery.

When the researchers compared survey responses in the two groups of women, they found that those who reported being "very worried" about recurrence were about twice as likely to have CPM as those who reported being "somewhat worried" or "not at all worried."

In addition, women who reported that they had tested positive for BRCA1 or BRCA2 mutations were about 10 times more likely to undergo CPM than those who did not have a mutation, and those having two or more first-degree relatives with breast cancer were about 4.5 times more likely to undergo CPM than those who did not have a strong family history of the disease. Although CPM reduces the risk of developing a new cancer in the unaffected breast for women with these clinical risk factors, the procedure has not been shown to reduce the risk of a recurrence of the original cancer.

"Our results suggest that many women are choosing a double mastectomy who really don't need it," Dr. Hawley said. "We want to make sure that women choose CPM…with a good, clear understanding of what it's doing and not doing in terms of risks and benefits…. What you do is a personal decision, but it should be an informed one."

Dr. Hawley and her colleagues are still analyzing the survey data and have not yet examined some other possible reasons that women may be opting for CPM.

"This study suggests that we should re-examine how we communicate with our patients regarding the decision of whether to undergo prophylactic mastectomy," said Dr. Jyoti Patel, an oncologist at Northwestern University who moderated a November 30 ASCO press briefing at the symposium.

This study was funded by NCI (CA088370 and CA109696).

Further reading: "Preventive Double Mastectomies Increasing Despite Some Concerns"

Higher Dose of Breast Cancer Drug Associated with Longer Survival

Women with advanced breast cancer who receive a higher dose of the drug fulvestrant (Faslodex) live longer than women who receive a lower dose, according to updated findings from a large clinical trial. The higher dose, 500 mg, has been in clinical use for a decade, but the new results provide evidence of a survival benefit for some women.

The trial, called CONFIRM, tested the two doses of fulvestrant in postmenopausal women with estrogen receptor (ER)-positive metastatic breast cancer whose cancer had recurred or progressed after previous treatment with endocrine therapy, such as tamoxifen (Nolvadex). Women who received 500 mg of fulvestrant lived for a median of 26.4 months, whereas women who received 250 mg lived for a median of 22.3 months, a statistically significant difference of more than 4 months.

The findings were presented December 5 at the San Antonio Breast Cancer Symposium (SABCS).

More than 700 women were enrolled in the international trial, which randomly assigned participants to receive 500 mg of fulvestrant or 250 mg, the dose initially approved by the Food and Drug Administration (FDA) in 2002.

The FDA approved the 500 mg dose in 2010, based on initial results from the CONFIRM trial that showed a statistically significant improvement in progression-free survival. Overall survival was also improved in the high-dose group, but the difference at that time was not statistically significant.

With longer follow-up, the overall survival benefit became statistically significant. But, the overall survival finding is from an unplanned exploratory analysis, warned the trial's lead investigator, Dr. Angelo Di Leo of the Hospital of Prato in Italy, during an SABCS press briefing.

Even so, when the results of the initial and updated analyses are compared, the two analyses "are perfectly consistent," he continued, "leading to the same conclusion that there is an increased benefit in terms of survival for patients receiving 500 mg" of fulvestrant.

Women who received the higher fulvestrant dose had a slightly higher rate of adverse side effects (8.9 percent versus 6.7 percent), but the difference was not statistically significant.

Following the FDA's 2010 approval, the 500 mg dose became the standard of care for this patient group, "so this study does not change current practice," said Dr. Claudine Isaacs of the Georgetown Lombardi Comprehensive Cancer Center. "However, it does provide further support for this dose and suggests that it may have a survival benefit."

Noninvasive Test for Kidney Cancer May Lessen Need for Surgery

According to a recent study, a new radioactive tracer agent can be used with positron emission tomography/computed tomography (PET/CT) to accurately detect clear cell renal cell carcinomas (ccRCC), the most common type of kidney cancer. The open-label study, conducted at 14 medical centers, was published December 3 in the Journal of Clinical Oncology.

"This study represents (to the best of our knowledge) the first clinical validation of a molecular imaging biomarker for malignancy," the researchers wrote.

The researchers compared results from two imaging methods in 195 patients with renal masses who were scheduled for kidney resections (nephrectomies): iodine-124 (124I)-girentuximab PET/CT and contrast-enhanced CT scans (CECT). 124I-girentuximab binds to an antigen that is found on the cell surface of nearly all ccRCC.

The investigators, led by Dr. Chaitanya Divgi of Columbia University Medical Center, reported that the 124I-girentuximab PET/CT tests were more sensitive than CECT (average sensitivity of 86.2 percent versus 75.5 percent) and more specific (average specificity of 85.9 percent versus 46.8 percent) for detecting ccRCC tumors.

If these results are confirmed by additional studies and the test is approved by the Food and Drug Administration, the new diagnostic test could lessen the need for more invasive procedures, including needle biopsies and nephrectomies, that currently are used to evaluate suspicious renal masses, the researchers suggested. 124I-girentuximab PET/CT may help practitioners decide how best to treat a patient and may have particular benefit for patients who are frail, elderly, or have other health conditions that make surgery risky, they commented.

Special Report

Experimental Drug Shows Promise against Drug-Resistant Leukemias

American Society of Hematology logo

An experimental drug called ponatinib may be a new treatment option for patients with chronic myeloid leukemia (CML) that is resistant to other therapies, researchers said Sunday at the American Society of Hematology (ASH) annual meeting in Atlanta. Patients with a type of acute lymphoblastic leukemia (ALL) that resists current treatments may also benefit from ponatinib.

The drug was designed to inhibit a range of mutant forms of the BCR-ABL fusion protein that are associated with drug resistance, as well as the unaltered form of the protein. This protein, which is derived from a genetic abnormality known as the Philadelphia chromosome, spurs the overproduction of white blood cells, a hallmark of CML.

"Ponatinib seems to be a very good treatment for patients who have run out of options because the other available drugs have failed," said Dr. Jorge Cortes of the University of Texas MD Anderson Cancer Center, one of the lead investigators. "The drug had a very high response rate in our studies, which included heavily pretreated patients."

The findings are from an ongoing phase II trial that included nearly 500 patients with relapsed or resistant CML or Philadelphia chromosome-positive ALL, which also expresses BCR-ABL. Ninety percent of the participants had previously received at least two BCR-ABL inhibitors, such as imatinib (Gleevec), dasatinib (Sprycel), or nilotinib (Tasigna).

Resistance to these drugs often occurs because of mutations in the BCR-ABL protein. Because of its chemical structure, ponatinib appears to be effective against all known mutations in BCR-ABL, including a mutation known as T315I, which is present in about 20 percent of patients with CML.

Consistent Results

Overall, the new results were consistent with those of a recent phase I clinical trial led by the same researchers. That study, which appeared in the November 29 issue of New England Journal of Medicine (NEJM), enrolled 81 patients with resistant blood cancers, including 65 with CML and 5 with Philadelphia chromosome-positive ALL.

In both trials, most patients experienced a complete hematologic response (all blood counts normal) while being treated with ponatinib, a pill taken once daily. More important, many patients achieved a complete cytogenetic response (no residual cells with the Philadelphia chromosome identified), the researchers noted.

"During the [phase I] trial, it was exciting to see responses in patients whose disease had progressed on all currently available treatments," said co-author Dr. Michael Deininger of the University of Utah Huntsman Cancer Institute. "The activity of this drug in these difficult-to-treat patients is really remarkable."

The side effects of ponatinib include a dose-related inflammation of the pancreas, which was manageable in nearly all cases, the researchers said. Another side effect was skin rashes, which were also generally manageable.

The results are "very encouraging," commented Dr. John M. Goldman of Imperial College London in an accompanying editorial in NEJM. He noted that ponatinib was a third-generation tyrosine kinase inhibitor that "could prove to be the best of the bunch for managing CML."

New Treatments Needed

The Food and Drug Administration (FDA) is reviewing ponatinib as a treatment for CML or Philadelphia chromosome-positive ALL that is resistant or does not respond to current therapies. (Update: The FDA approved ponatinib for these uses on December 14, 2012.) 

Considerable progress has been made in the treatment of CML since imatinib was introduced in the late 1990s, but new treatments are needed. "As good as current treatments for CML are, some patients don't do well over the long term," Dr. Cortes noted.

In about 25 percent of patients with CML, the disease does not respond to or becomes resistant to imatinib. Resistance is often caused by mutations in the BCR-ABL protein that prevent imatinib from binding to the BCR-ABL protein. About half of these patients benefit from the second-generation BCR-ABL inhibitors, dasatinib and nilotinib. But in many patients who initially respond to these inhibitors, the disease eventually becomes resistant to them as well.

An illustration showing how ponatinib fits into the targeted protein and an image of ponatinib's triple bond (Courtesy of the New England Journal of Medicine ©2012)Panel A: Ponatinib (blue and yellow spheres) fits in the binding cavity of the targeted protein (indicated by a mesh pattern). Panel B: The triple bond (yellow) is a unique structural feature of ponatinib (blue) that allows the drug to overcome the limitations of other BCR-ABL inhibitors. (Courtesy of the New England Journal of Medicine ©2012)

Ponatinib was an attractive drug to evaluate in the clinic, Dr. Cortes explained, because it was molecularly designed to overcome these limitations. "The drug has performed as we had hoped; it was very effective," he said.

More research is needed to determine how long responses to ponatinib will last and whether the drug causes toxic effects with long-term use. There are no data available on the use of ponatinib in the first-line setting, although a clinical trial has been launched to compare the efficacy of ponatinib and imatinib in patients with newly diagnosed CML in the chronic phase.

"If ponatinib gains regulatory approval, we may soon have a very good treatment for patients after the failure of dasatinib and nilotinib," said Dr. Deininger.

Ponatinib may have other uses as well. The drug targets a number of tyrosine kinases in addition to BCR-ABL, including KIT, PDGFRA, FGFR1, and FLT3, and may help treat tumors with mutations in the genes that make these proteins, Dr. Goldman noted.

"Ponatinib may turn out to be another step forward in the march toward real success with molecularly targeted therapy for cancer," he concluded.

Edward R. Winstead

This research was supported in part by the National Institutes of Health (CA016672).

Spotlight

Comparative Oncology: Man's Best Friend in More Ways than One

Adapted from an article that originally appeared in CCR Connections.

Prince (Photo courtesy of Frances and Peter Way) Prince (Photo courtesy of Frances and Peter Way)

It was nearly Christmas when Prince, an amiable, 9-year-old Labrador retriever was diagnosed with oral malignant melanoma. His owners, Frances and Peter Way, wanted the best treatment for their companion, so when veterinarians at Colorado State University's (CSU) Animal Cancer Center suggested a clinical trial, the Ways readily agreed.

Prince's melanoma was very aggressive, similar in many ways to human melanoma, and the Animal Cancer Center was part of a consortium, sponsored by the Comparative Oncology Program (COP) in NCI's Center for Cancer Research (CCR), through which dogs are treated with experimental therapies to prepare for their use in human clinical trials. Prince was treated with a new immunotherapy and achieved a robust response, living for almost a year.

"That's a lot longer than we think he would have otherwise," said Peter Way, from Fort Collins, CO. "We were hoping for a cure, but we also knew this would help the science, and I was glad that Prince could participate. It fit his spirit and his attitude; he was a great dog."

Addressing a Lost Opportunity

To date, the COP has treated more than 150 dogs over the course of nine clinical trials conducted through the Comparative Oncology Trials Consortium (COTC), a collaborative network of 20 veterinary schools around the country overseen by Dr. Melissa Paoloni. Dr. Chand Khanna conceived of the COP while he was a postdoctoral fellow in CCR, in the lab of Dr. Lee J. Helman.

At the time, Dr. Khanna was working on tumor metastasis and osteosarcoma, a bone cancer that occurs in pediatric patients and is also common in dogs. "It became clear to me that there would be great value in including pet animals with cancer within our CCR studies," he said. "There are very few human cancers that don't also occur naturally in pet animals. To me, not learning from their cancers to help inform human clinical trials seemed like a lost opportunity."

In 2004, with backing from Dr. Helman and Dr. Carl Barrett, then chief of CCR's Pediatric Oncology Branch and CCR's director, respectively, Dr. Khanna established the COP. Its mission, Dr. Khanna explained, is to improve the assessment of novel treatments for humans by treating pet animals—primarily dogs with naturally occurring cancers—while also trying to give these animals better quality of life by offering them the benefit of cutting-edge research and experimental therapies.

"The ultimate goal was for NCI to engage the drug development community and to lead a consortium of veterinary schools in a program to supply clinical research results that might accelerate new human treatments, and simultaneously help pet animals with cancer," Dr. Khanna said.

A Logical Partnership

According to Dr. Khanna, enrolling pet dogs in clinical trials has the potential to offer some key insights into human drug research. Dogs routinely develop osteosarcoma, lymphoma, bladder cancer, head and neck cancer, malignant melanoma, and mammary cancer. Moreover, human and canine cancers are very similar with respect to their genetics and biological features.

It became clear to me that there would be great value in including pet animals with cancer within our CCR studies.

—Dr. Chand Khanna

On a practical level, the compressed life span of a dog and the more rapid course of cancer progression make it easier for scientists to evaluate the benefit of novel cancer therapy in a short period of time. Repeat biopsies are often easier to perform in dogs than they are in people, making canine pre- and post-dosing tissue studies to investigate drug-target interactions feasible.

Additionally, thanks to the public release of the canine genome sequence in 2005, scientists can now understand the molecular changes that are associated with a treatment response and a treatment failure. And finally, the COTC studies spontaneously occurring tumors in pet dogs, which are far more similar to human cancer than tumors induced artificially in lab mice.

"It's also important to note that the COTC provides cutting-edge cancer treatment to pets whose owners might not otherwise be able to help them," said Dr. Paoloni. "It can cost thousands of dollars to pay for cancer therapy in a dog, and unfortunately that puts it out of reach for many families. So, our efforts can help both human and veterinary cancer patients."

Comparative Oncology Program Trials

Prince was enrolled in a study of two immunocytokine fusion proteins in tumor-bearing dogs, which aimed to define optimal doses and early indications of antitumor activity. "He'd get a monthly injection and then periodic blood work," said Dr. Susan Lana, chief of Clinical Oncology at Colorado State University Veterinary Teaching Hospital and Animal Cancer Center. "And we would follow the tumor as he progressed. Prince was a good candidate because, although his tumor was large, he was healthy in all other respects."

Led by Dr. Paoloni, COTC's first study investigated the safety and effectiveness of using a virus (or phage) to deliver tumor necrosis factor (TNF)—an inflammatory cytokine—directly into tumor blood vessels by intravenous dosing. TNF-alpha was already approved for local administration in human melanoma and soft tissue sarcoma, but with systemic dosing, human patients ran a high risk of hypotension and other cardiovascular reactions.

The phage was designed to avoid that problem by targeting a molecular marker on tumor blood vessels. Thus, the phage would theoretically spare normal vasculature and avoid cardiovascular and other toxicities. However, it was not practical to test the phage in healthy animals without cancer because animals lacking the tumor marker would simply excrete the phage.

Human and canine cancers are very similar with respect to their genetics and biological features.

During the trial, COTC scientists at five participating universities tested the phage in a pair of sequential studies. Those data are now being used as a basis for the first phase I clinical trial in humans, Dr. Paoloni noted.

According to Dr. Khanna, many COTC studies strive to predict appropriate human doses of new cancer drugs. "We want to know the relationship between dose and effect at a molecular level." Furthermore, he said, "There is a great need to answer simple questions that would optimize the success of future human trials. This can be as simple as: When is the best time to conduct a biopsy after dosing to see if a drug did what it was intended to do?"

In a pilot study that is nearing completion, COTC is investigating the feasibility of collecting, processing, and analyzing tissues from multiple sites for molecular markers in under a week, a clinically necessary timeline. According to Dr. Paoloni, this particular study will confirm COTC's future ability to participate in large-scale, molecular research in personalized medicine.

"It's crucially important that we can process tissues and generate accurate molecular readouts quickly," Dr. Paoloni said. "There are many examples of failures that may occur with sample processing in the era of targeted cancer therapy. You cannot underestimate how important it is to be able to collect samples correctly—otherwise the promise of personalized medicine will be difficult to realize."

Dr. Lana agreed, pointing out that in a "non-clinical world" it might take months to generate that kind of information. "Patients with cancer can't wait that long," she said.

This pilot study, Dr. Paoloni said, precedes a trial planned to determine if appropriate therapies can be prescribed on the basis of molecular profiling. Two more trials involve new areas of research for COTC investigators: one aims to determine whether advanced imaging technologies can predict molecular results obtained from tumor biopsies, and a second is focused on discovering the novel mechanism of action for a compound currently in the clinic.

Asked about long term plans for COTC, Dr. Paoloni envisions the future this way: "Essentially, we want to demonstrate the utility of this model so effectively that large pharmaceutical companies begin to develop their own comparative oncology programs. In that case, the COTC's role would be to oversee and advise on trials run by the pharmaceutical industry."

The Way family's opinion is that Prince was an active partner in the COP's research.

"It wasn't easy," they said. "Although we worked with great veterinarians in the program, it was emotionally hard to go through it. But we thought the program could benefit a lot of people, and that was important to us. We all have friends or family who have struggled with or died of cancer, and this was a positive thing for us and our dog to do."

Featured Clinical Trial

Treating Patients with High-Risk Smoldering Myeloma

Name of the Trial
Phase III Randomized Study of Lenalidomide Versus Observation Alone in Patients with Asymptomatic High-Risk Smoldering Multiple Myeloma (ECOG-E3A06). See the protocol summary.

Dr. Sagar LonialDr. Sagar Lonial

Principal Investigator
Dr. Sagar Lonial, Eastern Cooperative Oncology Group

Why This Trial Is Important
Multiple myeloma is a blood cancer characterized by the accumulation of plasma cells in the bone marrow (bone marrow plasmacytosis), monoclonal protein (M protein) in the blood and/or urine, and symptoms such as anemia, kidney damage, elevated calcium levels in the blood (hypercalcemia), and bone lesions. Although multiple myeloma can be treated, it cannot be cured with current therapies.

Occasionally people are found to have some level of bone marrow plasmacytosis and/or M protein, but they do not have the symptoms characteristic of multiple myeloma. Depending on the amount of M protein in the blood or the number of plasma cells in the bone marrow, these people are said to have either a benign condition known as MGUS or smoldering multiple myeloma. People with smoldering myeloma face a greater likelihood of progression to symptomatic myeloma.

Historically, multiple myeloma has been treated with very intense therapies, such as cytotoxic chemotherapy and stem cell transplantation, which carry a high risk of adverse side effects. Therefore, people with smoldering myeloma, many of whom may not need therapy for many years (if at all), are not treated until symptoms warrant it. Instead, they are managed with careful observation.

"Any time you have a patient who has no symptoms and give them a treatment, you run the risk of exposing them to side effects," Dr. Lonial explained. "It's hard to take a patient who feels well and make them better."

The development of newer, less toxic targeted drugs for multiple myeloma, however, has generated considerable interest among doctors and patients, raising hopes that treating smoldering myeloma could delay, or even prevent, progression to symptomatic disease.

"Organ damage has historically been the benchmark that we look for before we initiate treatment for myeloma," Dr. Lonial said. But by the time organ damage occurs, he continued, the disease is already causing problems, and symptoms, particularly bone lesions, can be painful and debilitating. "What we want to do is take those patients with a very high risk of progressing in a short time and see if we can prevent the kind of bad events—such as bone fractures, kidney failure, serious infections—associated with the conversion from smoldering to symptomatic myeloma.

"The availability of newer agents that are not only more active than chemotherapy but that also produce fewer side effects has encouraged us to revisit this concept of intervening earlier in a cohort of smoldering myeloma patients," said Dr. Lonial. "Furthermore, we are better at identifying those patients most likely to transform in a short period of time, and thus can focus more on the most 'at risk' population. These two developments, better treatment and improved identification of those who may gain the most from early intervention, have provided the impetus for investigators to try again to treat smoldering myeloma patients in the context of a clinical trial."

In this phase III clinical trial, patients with smoldering myeloma classified as high risk for progression will be randomly assigned to undergo standard observation or six 4-week courses of treatment with the drug lenalidomide, which will be taken daily for the first 3 weeks of each course. Lenalidomide is a targeted drug that disrupts the formation of new blood vessels (angiogenesis) and modulates the immune response to cancer cells. It was approved in 2006 to treat multiple myeloma based on studies that showed it delayed disease progression in patients who had progressed on or not responded to previous treatment.

"Our primary endpoint in this study is progression-free survival, or the difference in the time it takes to convert to symptomatic myeloma; however, an important secondary endpoint is quality of life," Dr. Lonial said. "We need to find out if there are side effects that make treatment unrealistic. If patients go longer before converting to symptomatic multiple myeloma but they end up having a poor quality of life, is that a worthwhile balance?"

For More Information
See the lists of eligibility 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/featured.

Profiles in Cancer Research

Dr. Titia de Lange: Telomere Function and Cancer

Leon Hess Professor 
Director, Anderson Center for Cancer Research
Rockefeller University

Dr. Titia de Lange Dr. Titia de Lange

When Titia de Lange was about 16 years old and living in Holland, she saw an electron microscope image of a chromosome in a Dutch newspaper. Seeing that image changed her life.

"I remember being completely struck by it," said Dr. de Lange. "Massive amounts of DNA were packaged in all of these endless loops. And our genetic information had to function within this element; that is how it has to work.

"But how could it work?" she said. "Everything I've done in my career goes back to that image and to that question."

Dr. de Lange began pursuing the answer as an undergraduate student. Organic chemistry was what she really wanted to focus on, but because there weren't many women in the field, and perhaps also because her grandmother was a biologist (who earned a Ph.D. in 1911), she chose biology instead.

Eventually, she found her way back to the molecular realm, first working with Dr. Richard Flavell, her undergraduate advisor at the National Institute for Medical Research in Mill Hill, London, and then with Dr. Piet Borst, her thesis advisor at the University of Amsterdam, who showed her how to manipulate DNA and to clone genes.

She then accepted a postdoctoral position in Dr. Harold Varmus' laboratory at the University of California, San Francisco, to learn more about genome instability in cancer. It was there that Dr. de Lange eventually focused her work on telomeres, which are long stretches of repeated nucleotide sequences that are found at the ends of linear chromosomes.

The End-Protection Problem

When a cell divides, it must copy its genetic information so that each daughter cell has its own set of instructions. But a small amount of DNA is lost from the ends of a chromosome each time it is replicated. The bits that are left off are part of the telomeres, which protect the chromosomes themselves from being degraded. Telomeres also prevent the ends of different chromosomes from fusing with each other.

In most normal cells, telomere degradation continues for 20 or 30 cell divisions until they become too short, at which point the cell stops dividing and eventually dies. In this sense, telomeres limit the lifespan of cells. In embryonic and adult stem cells, as well as many cancer cells, an enzyme called telomerase replenishes the telomere repeats lost during replication, keeping the cells alive indefinitely.

If telomeres don't work correctly, the chromosome becomes unstable, which can lead to DNA mutations, wholesale losses, and rearrangement of chromosomes that are characteristic of some cancers.

Chromosomes from a normal cell with unfused telomeres, and chromosomes from a cell in which the TRF2 protein in shelterin has been deleted, resulting in fused telomeres. The telomeres at the ends of normal chromosomes (left) are protected by a protein complex called shelterin, which helps chromosomes remain stable. When any of the proteins that compose shelterin are missing (right), the ends of telomeres can become fused or experience other changes that disrupt the normal growth cycle of the cell, in some cases leading to cancer.

Dr. de Lange studies the molecular and cell biology of telomeres and how telomere function is altered in cancer. In the early 1990s, after joining the faculty at Rockefeller University, she identified a binding factor on telomeres that she called TRF. Over the next 10 years, she and others isolated five more proteins that work together with this binding factor to form a complex named shelterin.

DNA has magnet-like stickiness and recombines easily when one end gets close to the end of a neighboring chromosome, which can cause structural rearrangements such as fusions and translocations. By protecting chromosome ends, shelterin prevents such rearrangements. It also keeps telomeres safely hidden from the machinery in the cell that would otherwise mistake them for chromosome breaks that need to be repaired.

The need to keep telomeres hidden so that chromosomes remain stable is known as the end-protection problem, and work in Dr. de Lange's laboratory has made substantial progress in terms of describing it.

"Now the question," she said, "is how does the [shelterin] complex do this? It's not trivial. Six proteins and six pathways mean six tricks. We think one trick is the t-loop"—physically, the telomere end is tucked back into itself as a loop, a finding that she and her collaborator, Dr. Jack Griffith at the University of North Carolina, Chapel Hill, first published in 1999—"but that would only take care of two pathways, and we still need to understand the other four. We have a big task ahead of us to figure out mechanistically how this complex does such a clever job."

Targeting Telomeres in Oncology: NCI's Investment

In principle, the telomeres of cancer cells should be an ideal target for cancer treatment. The enzyme telomerase is inactive in most adult cells, aside from stem cells, but about 80 to 95 percent of cancer cells use telomerase to extend their telomeres and to attain immortality. Other cancer cells use something called the ALT pathway to attain immortality.

"If we can selectively figure out how to block the mechanisms by which cancer cells overcome their natural limits, that would be almost like a magic bullet," said Dr. Richard Pelroy, program director in NCI's Division of Cancer Biology.

Several agents that target the enzyme telomerase are being tested in clinical trials, including small-molecule inhibitors, immunotherapies, and viral therapies. So far, none has shown the level of effectiveness that is hoped for, Dr. Pelroy said. "We need more-detailed molecular and mechanistic knowledge of what is happening at the telomeres during normal division and abnormal division."

To that end, NCI is funding basic research grants in this area, hoping to learn more about the risk factors that are associated with telomere dysfunction and cancer, as well as to refine the approach for targeting this potentially vulnerable feature of cancer cells.

Her recent work has described cellular features that may one day be used to home in on cells that use something other than expression of telomerase—namely, a process called the alternative lengthening of telomeres, or ALT, pathway—to prevent their own death. (See the sidebar.)

Science for the Right Reasons

Dr. de Lange's research has brought her accolades and wide recognition. During the last 12 or so years, "she's virtually defined the field of telomere protection," said Dr. Richard Pelroy, program director in the DNA and Chromosome Aberrations Branch of NCI's Division of Cancer Biology. "It was known that cells must be able to detect telomere dysfunction and deal with it in order to have normal cell division," he explained, "but the discussion was merely conceptual before her work."

For Dr. de Lange, life as a scientist is much easier now than it was when she first started down the path. As a young scientist, she had very little money and no laboratory assistance. "Nobody cared about telomeres," she said. "It was backwater research. We had meetings on telomeres in the early '90s—unofficial meetings, of course—and there were literally fewer than a dozen people who attended them."

What she did have, she said, was intuition and enthusiasm. "I loved telomeres," she said. "This is very important, to love something to death and be willing to do something important for it." That is the message that she tries to impress on everyone who works with her: Find your love in science first, and then good things will follow.

"She is 100 percent, fully dedicated," said Dr. Dirk Hockemeyer, an assistant professor at the University of California, Berkeley, who first worked with Dr. de Lange as an undergraduate exchange student from Germany and returned to earn his Ph.D. under her mentorship. "She's interested in really understanding how things work, and she won't let go until she's figured them out," he said. Dr. Hockemeyer recalled an example from 2006, when Dr. de Lange took a sabbatical from teaching so that she could work at the bench in her own laboratory and continue experiments that she had started 10 years earlier.

"She taught me to be happy with science for the right reasons," said Dr. Nadya Dimitrova, who did her Ph.D. work with Dr. de Lange. Dr. Dimitrova recalled that when she was writing her graduate thesis, Dr. de Lange "returned the draft to me and said that my conclusion and discussion weren't brave enough. 'You need to take this opportunity to say everything that you think…your whole model and hypothesis that goes even beyond your findings.' So, I started it all over and wrote a discussion that was far reaching and even prescient in some ways, and I'm very proud of that to this day."

Dr. de Lange doesn't believe that science has to be high risk in order to be satisfying, and she's careful not to pontificate about what one must do to attain success. But she does have one bit of advice for people who are considering careers in basic research.

"If you do a project just because you anticipate a high payoff, and you don't love the underlying science," she said, "I don't think you'll be able to sustain it. My advice is to find your own niche, one that you truly like, and then it doesn't matter so much. You'll do high-risk stuff, you'll do low-risk stuff, whatever is needed."

Which is exactly what happened in her case.

"I thought there would be bigger things to pursue eventually, but we're still working on telomeres," she said. "It's a much more complex and interesting subject than I ever could have anticipated."

Brittany Moya del Pino

FDA Update

Abiraterone Approval Extended to Treat Late-Stage Prostate Cancer

Men with castration-resistant prostate cancer that has spread can now be treated with abiraterone acetate (Zytiga) before receiving chemotherapy. The Food and Drug Administration (FDA) expanded the approved use of abiraterone on December 10.

The FDA initially approved abiraterone in April 2011 for use in patients whose prostate cancer had progressed after treatment with the chemotherapy docetaxel. Abiraterone is a pill that reduces testosterone production.

Testosterone stimulates the growth of prostate tumors, so drugs or surgery that reduce testosterone production or block testosterone’s effects are used to slow the growth of prostate cancer. However, most prostate cancers eventually become resistant to these treatments. These castration-resistant cancers continue to grow even when levels of testosterone are very low. Abiraterone is designed to treat these tumors by inhibiting the production of androgen in the testes, adrenal glands, and prostate cancer tumors themselves.

Abiraterone’s safety and effectiveness for its expanded use were established in a clinical study of 1,088 men with late-stage castration-resistant prostate cancer who had not previously been treated with chemotherapy. Participants received either abiraterone or a placebo (both in combination with the corticosteroid prednisone).

The study was designed to measure the length of time a patient lived before death (overall survival) and the length of time a patient lived without further tumor growth as assessed by imaging studies (radiographic progression-free survival, or rPFS).

Interim results from the study were published December 10 in the New England Journal of Medicine. According to an updated analysis cited in the FDA news release, patients who received abiraterone had a median overall survival of 35.3 months compared with 30.1 months for those receiving the placebo. The updated results, which have yet to be published, also showed abiraterone improved rPFS. The median rPFS was 8.3 months in the placebo group and had not yet been reached for patients treated with abiraterone at the time of analysis.

The most common side effects reported included fatigue, joint swelling or discomfort, swelling caused by fluid retention, hot flashes, diarrhea, vomiting, cough, high blood pressure, shortness of breath, urinary tract infection, and bruising.

The most common laboratory abnormalities included low red blood cell count; high levels of the enzyme alkaline phosphatase, which can be a sign of other serious medical problems; high levels of fatty acids, sugar, and liver enzymes in the blood; and low levels of lymphocytes, phosphorous, and potassium in the blood.

Cabozantinib Approved to Treat Rare Type of Thyroid Cancer

The Food and Drug Administration (FDA) approved cabozantinib (Cometriq) to treat medullary thyroid cancer that has spread to other parts of the body.

Medullary thyroid cancer is a rare type of thyroid cancer. The disease develops in cells in the thyroid gland that make a hormone called calcitonin, which helps maintain a healthy level of calcium in the blood. Cabozantinib is a kinase inhibitor that blocks abnormal kinase proteins involved in the development and growth of medullary cancer cells.

“Prior to today’s approval and the approval of [vandetanib] in April 2011, patients with this rare and difficult-to-treat disease had limited therapeutic treatment options,” Dr. Richard Pazdur, director of FDA’s Office of Hematology and Oncology Products, said in a news release.

The safety and effectiveness of cabozantinib were established in a clinical study that included 330 patients with medullary thyroid cancer. Patients treated with cabozantinib lived longer without the cancer progressing, and some experienced tumor shrinkage.

Patients who were given cabozantinib lived a median of 11.2 months without tumor growth compared with a median of 4 months for patients receiving a placebo. In 27 percent of patients treated with cabozantinib, tumors shrank, with the response lasting for a median of nearly 15 months, whereas none of the tumors shrank in patients who received a placebo. Treatment with cabozantinib did not extend patients’ lives.

The drug was approved with a boxed warning alerting patients and health care professionals that severe and fatal bleeding and perforations and fistulas in the colon occurred in some patients.

The most common side effects included diarrhea, inflammation or sores of the mouth, hand-foot syndrome, nausea, fatigue, new or worsening high blood pressure, and abdominal pain and constipation. The most common laboratory abnormalities included increases in liver enzymes, low calcium and phosphorus levels, and decreased white blood cells and platelets.

Notes

New National Cancer Advisory Board Members Named

Last week, President Barack Obama announced his intent to appoint the following individuals to the National Cancer Advisory Board (NCAB):

  • Dr. David Christiani, Elkan Blout Professor of Environmental Genetics, Harvard School of Public Health
  • Dr. Judy E. Garber, director of the Center for Cancer Genetics and Prevention, Dana-Farber Cancer Institute
  • Dr. Liz Jaffee, co-director of the Gastrointestinal Cancers Program, Sidney Kimmel Comprehensive Cancer Center
  • Dr. Beth Karlan, Board of Governors' endowed chair in Gynecologic Oncology, Cedars-Sinai Medical Center
  • Dr. Mack Roach III, professor of Radiation Oncology and Urology, University of California, San Francisco
  • Dr. Charles Sawyers, chair of the Human Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center

The NCAB is an 18-member advisory body that meets quarterly and advises the Department of Health and Human Services secretary and the NCI director on NCI activities.

NCI Recognizes 12 Clinical Investigators with Leadership Awards

NCI has announced the recipients of this year's Cancer Clinical Investigator Team Leadership Awards. These awards recognize 12 highly exceptional clinical investigators for their contributions to the advancement of clinical research through collaborative team science:

  • Dr. Lyudmila Bazhenova, UC San Diego Moores Cancer Center
  • Dr. Lisa Bomgaars, Dan L. Duncan Cancer Center
  • Dr. Alberto Broniscer, St. Jude Children's Research Hospital
  • Dr. Daniel DeAngelo, Dana-Farber Cancer Institute        
  • Dr. Konstantin Dragnev, Dartmouth-Hitchcock Norris Cotton Cancer Center
  • Dr. Shirish Gadgeel, Barbara Ann Karmanos Cancer Institute
  • Dr. Shannon Puhalla, University of Pittsburgh Cancer Institute
  • Dr. Bart Scott, Fred Hutchinson Cancer Research Center
  • Dr. B. Douglas Smith, Sidney Kimmel Comprehensive Cancer Center
  • Dr. Jonathan Strosberg, H. Lee Moffitt Cancer Center & Research Institute
  • Dr. Antoinette Tan, Cancer Institute of New Jersey
  • Dr. Jason Zell, Chao Family Comprehensive Cancer Center        

Designed for mid-level clinical investigators, these 2-year awards provide recognition and up to $50,000 in funding for those who lead cancer research programs and clinical trials at NCI-designated cancer centers. The funding is provided to the recipient's institution and is applied toward the investigator's salary, fringe benefits, and associated facilities and administrative costs. Recipients are expected to devote 10 to 15 percent of their time to the activities associated with the award.

The awardees are all actively engaged in NCI-funded collaborative clinical trials and collaborate freely across disciplines, institutions, and programs to advance the design and conduct of cancer clinical trials. The clinical researchers also serve as mentors and academic role models for trainees and junior faculty interested in clinical research and clinical trials.

This annual award opportunity, now in its fourth year, is the result of the recommendations of NCI's Clinical Trials Working Group (CTWG). The working group was established to advise the institute on methods to improve and enhance publicly funded cancer clinical trials.

Learn more about how NCI is restructuring the national cancer clinical trials enterprise online.

National Cancer Advisory Board Discusses NCI Funding Patterns, Program Updates

On November 28 and 29, the National Cancer Advisory Board (NCAB) met on the NIH main campus in Bethesda, MD.

NCI Director Dr. Harold Varmus opened the meeting with several updates, including the search for new leaders for the Division of Cancer Epidemiology and Genetics (DCEG), Center for Cancer Genomics, Center for Bioinformatics and Information Technology, and Center for Cancer Research's Medical Oncology Branch. He also spoke at some length about funding patterns, noting that about 15 percent of R01 applications and 10 percent of R21 applications were funded in 2012 and that the rate for renewals was about twice as high.

Dr. Varmus concluded his remarks with brief updates on several items, including the Recalcitrant Cancer Research Act of 2012, Provocative Questions Project, and the future of The Cancer Genome Atlas.

NCI Deputy Director Dr. Douglas Lowy then spoke about the need to increase human papillomavirus vaccination rates to prevent cervical cancer in the United States and elsewhere. He mentioned the Lasker Foundation's cervical cancer initiative and noted that Mexico will now offer the vaccine to all fifth-grade girls. "What governments decide to do could have immense impact," he said.

Dr. James Doroshow, director of NCI's Division of Cancer Treatment and Diagnosis, gave a brief update on the changes to the cooperative group program, noting that applications for the National Clinical Trials Network are due in mid-January. He also explained a new initiative on molecular identification that will take data from targeted drug trials in which fewer than 10 percent of patients had a response and try to identify why those patients responded.

The board also heard updates on DCEG, the Pancreatic Cancer Working Group, Frederick National Laboratory for Cancer Research, the Division of Cancer Prevention, and the NCI Community Oncology Research Program, a new program that will combine NCI's three community-based research networks.

The agenda and an archived videocast of the proceedings are available online. Videocasts of past meetings are available here.

NCI FY2013 Budget Proposal Published Online

cover of The National Cancer Program: Managing the Nation's Resesarch Portfolio–2013 NCI recently released The National Cancer Program: Managing the Nation's Research Portfolio, a request for support for fiscal year 2013.

This report, which constitutes NCI's annual plan and budget proposal for current and future cancer programs, is presented directly to the president and Congress. The document summarizes many of the contributions that NCI has made to cancer research and their practical consequences.

This year's report also describes some of NCI's broad research programs that address a wide range of cancers and their underlying biological properties, and it discusses five specific types of cancer that exemplify the various strategies to address the different diseases and the progress being made.

NCI E-Books Available on Mobile Website

e-book reader E-book versions of many popular NCI patient education publications are now available on NCI's mobile website, m.cancer.gov, making it easier to download and read them on a smartphone, tablet, or e-reader.

  • On your device, go to the E-Book  Library to see a list of currently available e-books.
  • Click the title of an e-book. The next page will have two links for that title: one for Kindle and one for other e-readers (Nook, Sony e-Reader, Kobo, etc.).
  • Click the format that will work with your device, or click a reader app on your smartphone or tablet to download and open the file.

New e-books are being added frequently, so check NCI's e-book page often.

Annual Report on NCI Disparities Research Released

cover of NCI Center to Reduce Cancer Health Disparities: Annual Report for Fiscal Year 2011NCI's Center to Reduce Cancer Health Disparities (CRCHD) has just released its Annual Report for Fiscal Year 2011. The new report describes the impact of CRCHD's efforts to enhance the understanding of the biological and nonbiological causes of cancer health disparities, increase the diversity of the cancer research workforce, and reduce the unequal burden of cancer that still exists in this country.

The report also outlines CRCHD's fiscal year 2011 programs, and selected projects, investigators, and partnerships that represent the variety of research addressing different cancers, training, and community outreach efforts supported by NCI/CRCHD grant mechanisms.

The investigators, projects, and partnerships profiled in the report illustrate the range of efforts and significant strides being made to address the goal of eliminating disparities.