Articles

Amgen Honored for Best Pipeline & Best New Drug

Do Insurers Spend Too Much on Administration and Too Little on Care?

The Effect of New Treatments on Cancer-related Bone Loss

Mixed results for targeted agents in breast cancer

This activity reviews the results of several studies presented at the 32nd Annual San Antonio Breast Cancer Symposium (SABCS) that assessed targeted therapy plus chemotherapy in patients with advanced breast cancer; these studies yielded mixed results. Upon reading the article, participants must correctly answer two multiple-choice questions to receive credit. 

Benefits of bevacizumab modest in metastatic disease

This activity reviews two studies presented at SABCS that showed only a limited increase in survival when bevacizumab was added to a chemotherapy regimen for patients with metastatic breast cancer. Upon reading the article, participants must correctly answer two multiple-choice questions to receive credit. 

HER2 combo boosts metastatic breast cancer survival

This activity is based on a study presented at SABCS that shows that a dual biologic attack on heavily pretreated metastatic breast cancer with lapatinib and trastuzumab may substantially prolong survival, without chemotherapy or endocrine therapy. Upon reading the article, participants must correctly answer two multiple-choice questions to receive credit. 

www.medpagetoday.com/MeetingCoverage/ SABCS/17536 

Vitamin D reduces aromatase inhibitor pain

This activity is based on a study presented at the 2009 American Society of Hematology (ASH) annual meeting that indicated that a highdose of vitamin D might relieve musculoskeletal pain caused by treatment of breast cancer with aromatase inhibitors. Upon reading the article, participants must correctly answer two multiple-choice questions to receive credit. 

*More SABCS CME opportunities are available at medpage Today at www.medpagetoday.com/ MeetingCoverage/SABCS.

Surgical approach to liver-limited metastatic colorectal cancer

Participants are required to read an E-Update in which experts write about recent liver-limited colon cancer advances. The update discusses biologic, surgical, and toxicity issues in liver-limited disease. Successful completion of a posttest with a passing score of 80% or better earns the participant the credits. The activity in its entirety should take approximately 2 hours to complete. 

Management of small renal masses: What is the best management option in this case? 

At the conclusion of this activity, participant will be able to contrast the benefits and pitfalls of specific management options for patients that present with an incidental renal mass, including radical nephrectomy, partial nephrectomy, energy ablation, and active surveillance; discuss the potential morbidity associated with active surveillance strategies, including the risk of local and metastatic progression; and explain issues of patient selection for appropriate management for a small renal mass. 

Innovations and challenges in renal cancer 

Following completion of this activity, participants should be able to discuss how recognized molecular targets in renal cancer are related to prognosis and current and future therapeutic approaches; discuss current approaches to prognostic classification in renal cancer as they relate to treatment selection and expectation; and assess recent clinical data for immunotherapies and targeted and anti-angiogenic therapies in renal cancer treatment.

Management of stage III, N2 NSCLC: A virtual thoracic oncology tumor board

This Webcast-based activity features a team of multidisciplinary medical experts in a virtual tumor reviewing the case of a 55-year-old man with stage III, N2 non—small cell lung cancer (NSCLC). The goal of this activity is to demonstrate the many different options available for staging and treating such cases by examining current and emerging strategies in the management of patients with lung cancer. After completing this activity, participants will understand how to assess, diagnose, and stage lung cancer using the newest staging systems, tumor node metastases classification, tumor location, performance status, and surgical respectability to determine the stage-specific treatment methods. Participants will also be able to describe the appropriate use of chemotherapeutic agents and radiation therapies in treatment strategies for lung cancer patients that improve outcomes through knowledge of their efficacy and safety, and integrate targeted therapies into more successful treatment regimens for patients with lung cancer by evaluating the safety and efficacy of these agents. 

Treatment paradigms in advanced non-small cell lung cancer: The evolving role of maintenance therapy 

This activity focuses on different treatments and therapies used to manage various stages of lung cancer. Upon completing this activity, participants should be able to use MAbs and EGFR/TK inhibitors in the front-line treatment of lung cancer. They should also have a better understanding of how to effectively use maintenance chemotherapy in the treatment of lung cancer. 

Review of evidence-based support for pretreatment imaging in melanoma

Upon completion of this activity, participants will be able to identify prognostic factors in patients with newly diagnosed melanoma; define the recommendations for pretreatment imaging from the National Comprehensive Cancer Network in patients with melanoma; describe the types of pretreatment imaging techniques used in patients with melanoma; describe imaging techniques for identifying regional lymph node metastases in patients with newly diagnosed melanoma; and describe biochemical tests used for assessing prognosis in patients with melanoma. 

http://cme.medscape.com/viewarticle/591010

A reappraisal of the significance of largest basal diameter of posterior uveal melanoma 

Upon completion of this activity, participants will be able to describe the features of uveal melanoma likely to be predicted by largest tumor diameter, identify the most common treatment strategies for uveal melanoma, describe mortality associated with chromosome deletions and gains in patients with uveal melanoma, and describe the histologic and demographic factors associated with metastatic death from uveal melanoma, describe the predictive value of largest tumor diameter for disease-specific mortality in patients with uveal melanoma. 

http://cme.medscape.com/viewarticle/711172

Saliva test for microRNA could detect oral cancer

This activity involves reading a short news story discussing a study that examined miRNAs in saliva as oral cancer biomarkers and answering two multiple-choice questions. Upon completing the activity, participants should be able to discuss the results of this study and review its relevance and significance in the broader context of clinical care. 

This activity requires reading a short news story and answering two multiple-choice questions on an article published in the Journal of the National Cancer Institute that found that diets high in fat, especially fat from meat and dairy products, were linked to an increased risk of pancreatic cancer. Upon completing this educational program, participants should be able to discuss the results of this study with their patients and review the relevance and significance of the study in the broader context of clinical care. 

Improving outcomes in pancreatic cancer: Existing options and novel approaches

Upon completing this educational activity, participants should be able to discuss the diagnostics involved in the staging process for pancreatic cancer and how this knowledge provides opportunity to more accurately diagnose pancreatic cancer in early stages; incorporate national clinical guidelines regarding surgical resection and adjuvant therapy into management plans that address preoperative, intraoperative, and postoperative concerns; and discuss clinical trial data results from new combinations of existing treatments and novel targeted therapies for pancreatic cancer. 

www.mdedu.org/online/Pancreatic_Cancer.html

New treatment paradigms in pancreatic cancer

Upon completing this activity, participants should be able to apply an adjuvant treatment framework based on scientific studies, analyze the role of radiation therapy in locally advanced pancreatic cancer, demonstrate an understanding of the current treatment options for metastatic pancreatic cancer, appraise novel treatments currently being studied, and deliver optimal palliative care to patients with advanced pancreatic cancer. 

Clodronate improves survival in metastatic prostate cancer

Upon completing this activity, participants should be able to explain to patients that treatment with sodium clodronate improved overall survival in men with metastatic prostate cancer to bone. This finding is based on the results of a trial published in the August 11 issue of The Lancet Oncology. Upon reading the article, participants must correctly answer two multiple-choice questions to receive credit. 

Continuing Education Opportunities on the Web

Exercise Maintains Function, Improves QoL for Patients With Lymphoma

Ramucirumab is an investigational immunoglobin G1 (IgG1) monoclonal antibody (mAb) currently under development. It uses only human cells, allowing it to avoid many of the adverse effects associated with murine or chimeric mAbs. Ramucirumab binds to human VEGFR-2, thus blocking VEGF binding and thwarting the angiogenic process. It is thought that inhibiting VEGFR-2 might yield superior outcomes in several solid tumors. Ramucirumab has demonstrated activity in vitro and in murine models against leukemia and ovarian cancer cell lines and in phase I and II clinical trials against breast and gastric cancer. 

Ramucirumab inhibits VEGFR-2 expression from normal endothelial cells, as well as tumor endothelial cells, impairing endothelial healing and hypercoagulability. Preliminary data suggest that ramucirumab is well tolerated, with manageable adverse effects. The safety of ramucirumab has not been reported on extensively, however, and results from the many ongoing studies should shed light on this important area. Its specific targeting of VEGFR-2 suggests it may have a narrower adverse effects profile than broadspectrum TKIs. 

VEGF inhibition increases the risk of bleeding events, as seen with bevacizumab (Avastin), another mAb that inhibits VEGF expression. Hypertension and renal toxicities are also not unexpected with ramucirumab. Based on safety data from trials of bevacizumab, investigators decided to exclude certain patient populations from subsequent trials of ramucirumab. These include patients who have brain metastases, a recent history of thrombotic events, non-healing wounds/ulcers, major blood vessel encasement or invasion.

In this multicenter, multinational study sponsored by ImClone LLC, investigators plan to accrue 1113 patients with recurrent HER2-negative locally advanced or metastatic breast cancer (MBC) or inoperable breast cancer. Patients will be randomized to receive docetaxel plus the investigational agent ramucirumab or placebo. Patients must not have received prior therapy for their recurrence or MBC. Treatment will continue until evidence of progressive disease or unacceptable toxicity. Patients will be assessed every 6 weeks until progressive disease and every 6 months thereafter for at least 36 months after discontinuing the study. 

Investigators hope to assess overall survival of patients with metastatic gastric cancer (including cancers of the gastroesophageal junction) who are randomized to receive treatment with ramucirumab and best supportive care (BSC) or placebo and BSC. They plan to enroll 615 patients whose disease has progressed following first-line treatment with a platinum- or fluoropyrimidine-based chemotherapy regimen. Treatment will continue until evidence of progressive disease, unacceptable toxicity or failure to adhere to protocol. Secondary outcome measures include progression-free survival, objective response, duration of response, quality of life, and safety. 

Investigators seek to determine whether the investigational agent IMC-A12 or ramucirumab plus mitoxantrone and prednisone are effective in metastatic androgen-independent prostate cancer in patients whose disease has progressed after docetaxel-based chemotherapy. In this randomized study, 132 patients will be randomized to receive one of the two experimental drugs plus mitoxantrone and prednisone. Treatment will continue until evidence of disease progression, intolerable toxicities, or death. IGF-IR and VEGFR-2 mediated pathways may contribute to prostate cancer pathogenesis. Patients with other malignancies are excluded from participation. 

In this interventional open-label study sponsored by the National Cancer Institute and ImClone LLC, investigators plan to enroll 80 patients with brain and central nervous system tumors, particularly recurrent glioblastoma multiforme. One group will receive ramucirumab administered intravenously; the other group will receive anti-PDGFR alpha monoclonal antibody IMC-3G3. Both treatments will be continued until disease progression or unacceptable toxicity. The primary outcome measure for this trial is progression-free survival at 6 months. Secondary outcome measures include objective tumor response rate, overall survival, acute and late toxicities, and Pharmacokinetic and pharmacodynamic profiles and immunogenicity. 

VEGF is a polypeptide found on chromosome 6p12. Cells trigger production of this protein to stimulate the growth of new blood vessels, a vital function that promotes healing when blood vessels are injured or occluded or when tissue is hypoxic. Various cellular receptors and oncogenes contribute to increased VEGF expression. VEGF overexpression sometimes leads to vascular disease or the unchecked growth of malignant tumors. 

Most cancerous tumors secrete VEGF, which signals angiogenesis and facilitates survival of a tumor’s existing vasculature. VEGF signaling enables tumors to establish their own vascular support network, securing an unimpeded supply of nutrients and oxygen. This facilitates tumor growth and infiltration into surrounding tissues. Tumor vasculature associated with high levels of VEGF expression is typically abnormal, with leaky pericytes, tortuousness, and hyperpermeability. The tumor’s immature and abnormal vessels can impede the effective delivery of anticancer compounds. 

Current understanding is that there are five VEGF ligands, identified as VEGF-A through VEGF-E. The first to be discovered was VEGF-A, which is considered the most critical to neovascularization and is typically referred to simply as VEGF. This protein binds to VEGF receptors (VEGFRs) 1 and 2 on the surface of endothelial cells (Figure). VEGFR-2 has also been found on the surface of tumor cells in some malignancies. The binding of VEGF to VEGFR-2 causes dimerization and activation through transphosphorylation. 

Endothelial cells in tumor blood vessels can express VEGFR-1, VEGFR-2, and VEGFR-3, though they primarily express VEGFR-2. The upregulation of VEGFR-2 is common during tumor formation and growth. VEGFR-2 expression is said to be 3- to 5-fold higher in tumor vasculature than in normal vasculature. It is believed that, of the three VEGFRs, only VEGFR-2 triggers intracellular signaling, making it a useful pathway to target for inhibition. 

Ramucirumab is an investigational immunoglobin G1 (IgG1) monoclonal antibody (mAb) currently under development. It uses only human cells, allowing it to avoid many of the adverse effects associated with murine or chimeric mAbs. Ramucirumab binds to human VEGFR-2, thus blocking VEGF binding and thwarting the angiogenic process.

Ramucirumab (IMC-1121B): A Novel Fully Human Monoclonal Antibody that Targets VEGFR-2

A study at the University of Texas M.D. Anderson Cancer Center has found that paclitaxel may significantly increase the risk of neuropathic pain in breast cancer survivors. Of 240 breast cancer patients surveyed who participated in clinical trials of paclitaxel between 1994 and 2001, 64% experienced neuropathic pain during treatment, while 27% were diagnosed post-treatment with chronic neuropathic pain. Researchers concluded that neuropathic pain at the time of chemotherapy could indicate a risk for chronic neuropathic pain and these patients should be regularly monitored after treatment. The study is published in the November issue of 

Many breast cancer survivors avoid eating soy because studies suggested it might induce estrogen-like activity. A study of 5000 Chinese breast cancer survivors published in the 

Journal of the American Medical Association

 says women should eat more soy, not less. The women were tracked for 4 years and those who ate the most soy had the lowest rates of recurrence and death regardless of whether the primary tumor was estrogen-positive or estrogen-negative. 

A panel formed to advise the FDA is deciding whether all or some of the 7 gadolinium-containing contrast dyes approved to enhance MRI images should be restricted to individuals without severe kidney problems. Among the drugs being debated are General Electric Co’s Omniscan, Bayer’s Magnevist, and Covidien Limited’s Optimark. The FDA has said that these products put patients with severe kidney disease at increased risk for the potentially fatal skin condition known as nephrogenic systemic fibrosis. The FDA updated labeling for these drugs in 2006 to warn against their use in these patients but use was still allowed at the physician’s discretion. Gadodiamide and gadoversetamide are considered two of the dyes with the highest risk for patients with impaired renal function. 

The University of Maryland’s School of Medicine transplanted donor kidneys from patients with kidney cancer into 5 individuals with end-stage renal failure. All these patients were at death’s door, waiting for a healthy donor. The surgeons removed all traces of the tumors from the cancer-riddled kidneys prior to surgery, and after 9 to 41 months, none of the renal patients has developed cancer. One died from an unrelated accident. Michael Phelan, who co-authored the study said, “The global increase in patients with end-stage renal disease” meant looking at other ways to increase the donor pool. 

FDA Requests Plan from Opioid Manufacturers

Sixteen pharmaceutical companies that manufacture a cumulative 24 painkillers—including optimorphine, oxycodone, and methadone&mdash;collaborated on a joint risk-management plan for preventing opioid abuse, which they submitted to the FDA. The regulatory agency ordered the companies to develop a plan to help stem the tide of deaths from painkiller overdose. The manufacturers suggested providing medication guides for patients and additional training for physicians on the appropriate uses for opioids. According to a 2007 survey, 5.2 million Americans admitted using painkillers inappropriately. Patients’ rights groups are worried that making requirements burdensome on physicians may inhibit them from prescribing the drugs to patients who genuinely need them.

Researchers at the University of Melbourne, Australia, and the University of Innsbruck, Austria, are studying kangaroos’ response to ultraviolet light exposure in the laboratory to figure out why kangaroos do not get melanoma. They have found that kangaroos produce an enzyme that repairs DNA damage after sun exposure. Other animals also produce similar enzymes, but humans do not. The researchers said they’ve discovered a number of new chemicals in their studies and hope to someday be able to replicate these. 

 granted orphan drug status by the FDA for Abraxane (Nab-paclitaxel) in stage IIB-IV melanoma. Abraxane is already approved for breast cancer and was granted orphan drug status in September for pancreatic cancer. Abraxis plans to test Abraxane in a phase III study versus dacarbazine in patients with chemotherapy-naïve advanced melanoma. 

 has been approved by the FDA to treat cutaneous T-cell lymphoma. Istodax is a new injectable medication, and 35% of patients in two clinical studies demonstrated tumor responses lasting a median of 11 to 15 months. In addition, 6% had complete response. 

 new drug application for CEQ508 has been approved, allowing the company to move forward with trials of the drug in patients with familial adenomatous polyposis. This trial will be the first ever for an orally administered RNA interference drug in humans. Based on proprietary tkRNAi technology, CEQ508 targets beta-catenin, a key oncogene in colonic polyp formation and the progression of polyps to colorectal cancer. 

 has been granted to KRX-0401, also known as Perifosine. The drug is in phase II mid-stage clinical development for multiple tumor types; investigators are preparing to commence a phase III late-stage trial for multiple myeloma. Earlier this year, the FDA gave Perifosine orphan drug designation. AEterna Zentaris of Quebec, Canada, and Keryx Biopharmaceuticals Inc of New York are partnering on the drug in North America. 

 and Renal Drugs Advisory Committee recommended 11 to 1 that the FDA approve Novartis’ Afinitor (everolimus) to prevent organ rejection in patients who have undergone kidney transplants. An advisory panel suggested that the company adopt a risk-management plan to minimize the drug’s potential side effects. 

 biopharmaceutical company Teva is seeking FDA approval of a Biologics License Application for XMO2 (marketed in Europe under the name TevaGrastim) for the treatment of chemotherapyinduced neutropenia. The drug is a biosimilar of Amgen’s Neupogen (filgrastim). The FDA does not currently have an established pathway for securing regulatory approval of a biosimilar drug, and Amgen may legally oppose the filing. 

Capsule summaries of current issues and developments in breast cancer, kidney disease, supportive care, and melanoma are presented, as well as timely updates on FDA actions and approvals.

News Briefs & FDA Updates

In the current national healthcare reform debate, few issues have generated more opinions and greater confusion than the value of cancer screening such as for prostate and breast cancer. Breast cancer mortality has decreased by 27% since the early 1990s, likely the result of earlier diagnosis with screening and better treatment options. Nevertheless, skepticism has recently been voiced about the value of breast cancer screening, which, along with persistent financial and educational barriers, has led to a decline in mammography screening rates despite clear recommendations from the American Cancer Society and several medical professional organizations.* The federally funded US Preventive Services Task Force (USPSTF) has until now fully supported such recommendations. Mysteriously, and reading somewhat like a John Grisham or Dan Brown novel, the USPSTF has reversed several long-held key recommendations for breast cancer screening. Despite little new data and no change in estimates of benefit and harm, the USPSTF now recommends against screening in the 40- to 49-year age group, screening in older women only every other year instead of annually, and explicitly recommends against teaching women breast self-examination (BSE). So, why has the USPSTF reversed its positions on such important issues that fly in the face of other US recommendations including their own? 

A few clinical trials have updated their results, and one new study in the 40- to 49-year age group from the United Kingdom reports an estimated reduction in the risk of breast cancer mortality at 10 years of 17%, virtually identical to that of earlier trials considered by the USPSTF. In fact, in the most recent trial, adjustment for incomplete adherence with screening led to an achievable reduction in breast cancer mortality in women aged 40 to 49 years of nearly 25%. After considering potential harm from false positive results and low-level radiation exposure, the net benefit was found to exceed any harm over a broad range of assumptions. 

The USPSTF now considers this reduction in mortality to be “small” in this age group, which they balance against “moderate” potential harm from unnecessary biopsies. Most oncologists would consider a treatment reducing breast cancer mortality by 15% to 25% a breakthrough. While there is no evidence that occasional negative biopsies cost lives, failure to diagnose early-stage breast cancer does. While recent advances have focused on less surgery and a more personalized approach, we are not yet able to safely identify patients with breast cancer who do not require treatment. It is premature and somewhat reckless to suggest that some invasive breast cancers are not life threatening and do not require treatment. The USPSTF now recommends screening older women every 2 years rather than annually. While the clinical trials varied in the screening interval from every year to more than 2 years, it is not possible to directly compare the value or loss of benefit to less frequent screening in those trials. While such a change could save costs in the short term, the additional confusion and uncertainty may lead to further declines in screening rates, while even a small increase in more advanced disease may have an eventual adverse effect on both women’s lives and healthcare costs. 

Perhaps the most puzzling change in recommendations from the USPSTF relates to BSE, which, despite no new data, they now explicitly recommend that women NOT be taught. While it is true that two large trials on this subject found no reduction in mortality, they were conducted in very different cultures and health systems and have questionable relevance to a US setting. While the potential for harm and costs are negligible, countless women have found their cancer through self-examination months or even years before it would have likely come to medical attention at a more advanced stage. Why would the USPSTF recommend against patients being taught a simple, safe, and inexpensive procedure that may be life saving? Go figure. 

While some will conclude that these misguided recommendations are an early attempt to ration healthcare, they more likely reflect the need for input from practicing cancer specialists with expertise in the diagnosis and treatment of breast cancer. Whatever the cause, these new and conflicting recommendations are likely to lead to greater confusion and reduced breast cancer screening, reversing decades of effort to reduce the devastating impact of advanced breast cancer on the lives of tens of thousands of women in this country each year. Should the Center for Medicare and Medicaid Services and other insurers act on these new recommendations, reversing hard-fought reimbursement policies for breast cancer screening, it will be a major step backward, not forward, in the war against cancer. Efforts to improve the survival and quality of life for women with breast cancer require the rational application of all effective strategies in a cost-effective manner, including breast cancer screening. 

*American College of Physicians, the National Comprehensive Cancer Network, the American Medical Association, the American Academy of Family Physicians, the American College of Obstetrics and Gynecology, the Canadian Task Force on Preventive Health Care.

Prevention and Treatment of Venous Thromboembolism in Patients with Cancer

, MPH, FRCP (Edin) is Professor of Medicine and Director of Health Services, Effectiveness and Outcomes Research in Oncology at Duke University and the Duke Comprehensive Cancer Center, where he is also Senior Fellow at the Duke Center for Clinical Health Policy Research. Dr Lyman serves as a member of both the ASCO Cancer Education and Health Services Committees, chairing the Methodology Subcommittee as well leading several clinical practice guideline panels, including the recent ASCO Guideline on 

. Dr Lyman is a member of the Oncology Drug Advisory Committee (ODAC) to the US Food and Drug Administration. He is Editor-In-Chief of 

. He is also on the editorial advisory board of 

. The recent media coverage of the United States Preventive Services Taskforce (USPST) mammography guidelines alludes to the “controversy” within the medical community regarding the value of mammography in screening women in the 40- to 50-year age range. First, there is no controversy; second, this is not a political issue. The subject places well-informed physicians in a better position to address their patients’ needs by explaining the nature of the debate to inquiring patients. 

Our Role in How the Mass Media Covers Cancer Stories

There was a time when oncologists learned the latest information about potential risks of cancer and new treatment ideas at major cancer meetings. Nowadays, we’re likely to first learn about these issues from a news report—and often in the business section!&mdash;or from patients directly. What is particularly challenging is that these stories are often reported in extreme terms: Coffee Prevents Cancer! Coffee is Poisonous! Miracle Cancer Treatment Discovered! In fact, if you only watched the headlines, you might think a new miracle cancer treatment was ready to hit the shelves just about every week. 

This leaves oncologists with the unenviable task of needing to apply context when our patients respond breathlessly to the typically unjustified promises or fears these stories generate. Oprah, the network news science correspondent, or even a 

 report may lead our patients to believe that the next big breakthrough is right around the corner, forcing us to act as that wet blanket reminding them of the big difference between encouraging early lab-based work in cell cultures or mice and validated clinical research in real human cancer patients. 

I give credit to the authors of a recent editorial in the 

 by Woloshin and colleagues (2009;101(23):1595) for highlighting the problems with how the media handle reporting about cancer. It describes reasons why far too much new information is presented in such sensationalized terms. The authors note that willful misrepresentation in hopes of generating viewership/readership is part of the issue; another is the fact that many journalists lack the knowledge required to place the findings in the proper context. 

Many of our research reports only reference the relative risk or benefit (ie, 30% higher risk of developing cancer or 20% improvement in survival) without noting the effects in absolute terms. If a press release is deliberately ambiguous, it’s the fault of the investigators or those writing the press release if journalists merely echo what they see, highlighting a “20% improvement” without noting the limitation that this difference may amount to only 3 weeks in absolute terms or that a doubling of risk of developing a rare cancer may mean that the risk escalates from 0.1% to 0.2% over a person’s lifetime. 

Another common media practice is to obtain a quote or two, often from the person who led the research effort. When you think about it, it would be hard to find anyone more likely to be biased about the importance of the work than the person who led the study. I consider it particularly frustrating and potentially unethical for an investigator involved in very early research that is years away from being vetted in appropriate clinical trials to declare that the work represents a breakthrough for cancer patients. This may just be a case of investigators who cannot be objective because it is their research (just as most of us think our own children are smart and beautiful), or it may be motivated by the desire to leverage the attention into more research funding and an opportunity to achieve greater recognition in the field. If an opinion is sought from someone unlikely to be impartial, it makes sense to corroborate or counterbalance the investigator’s self-congratulatory commentary with an alternative view from another expert in the field. 

Another recommendation included in the editorial is that journals demand that investigators describe the limitations of their own work and/or that the journal offer some context for the data. The Annals of Internal Medicine has recently started to pursue such a policy, but they are ahead of the curve in this respect. There are certainly some journalists who demonstrate the sophistication and dedication to cover the gray areas of a topic and highlight the limitations of early research. We should strive to educate journalists on how to vet a story and provide greater balance. Meanwhile, medical researchers could generate coverage that is more evenhanded by offering more context and less grandstanding. We need to convey to the general public the need to be wary of simplistic spoon-fed solutions, whether they represent fear-mongering or tout this week’s miracle cancer treatment. Dispelling the myth of the definitive, easy answer in oncology is about as much fun as telling kids that there really isn’t a Santa Claus. But these are our patients, and it is our responsibility to treat them with something other than magical wishes. 

 is a medical oncologist and medical director of the Thoracic Oncology Program at the Swedish Cancer Institute in Seattle, Washington. He also serves as president of the nonprofit organization Global Resource for Advancing Cancer Education (GRACE), 

Breast Density & Not Age the Best Predictor of Mammography’s Usefulness

The recent media coverage of the United States Preventive Services Taskforce (USPST) mammography guidelines alludes to the “controversy” within the medical community regarding the value of mammography in screening women in the 40- to 50-year age range. First, there is no controversy; second, this is not a political issue. The subject places well-informed physicians in a better position to address their patients’ needs by explaining the nature of the debate to inquiring patients. 

We know that data-driven studies show mammography can prevent death from breast cancer in 25% to 30% of appropriately screened women. We also know that mammography is not infallible and misses 1 in 5 of even palpable breast cancers. Most missed cancers are in women under age 50. To that end, the shift in screening from film mammography to digital mammography best improved the detection rate of breast cancers in this age group. However, when the population benefit of screening mammography is addressed in an impartial, data-driven manner, the information revealed by the USPST is correct: mammography, as we have always known, is not as reliable in women under age 50 as it is in women older than age 50. The question for well-informed physicians is how to use this information wisely. 

The limitations of mammography have less to do with age than with the density of the woman’s breast. Until recently, when research has begun to elucidate the primacy of breast density on the risk of breast cancer, age alone was used to define the risk of breast cancer. Yet, because dense breast tissue is more often noted in women under 50, the accuracy of mammograms in younger women is inferior to that seen in older woman, whose dense breast tissue has undergone the typical postmenopausal changes that make the breast more fatty, less dense, and therefore easier to “see through.” 

Many women under age 50 have fatty breast tissue, and mammography in these women proves as reliable and accurate as it tends to be in older women. The converse may also be true. A 60-year-old woman on hormone replacement therapy may have such dense breast tissue that her mammogram may not be very accurate compared with other women her age. Yet her exceptional examination does not render screening mammography useless for other women in her age group. 

Physicians must be aware of the limitations of mammography and design a screening strategy that best suits an individual woman’s risk of breast cancer. Once a risk assessment is obtained, the physician can decide whether mammography is useful as part of her overall preventive strategy, regardless of age. If a patient’s mammogram shows fatty, easy-to-see-through breast tissue, mammography should be part of her individual risk prevention strategy. If she has a very dense breast and mammograms add little benefit, she needs a better strategy that perhaps uses mammograms every 2 years or longer or involves other ancillary examinations until the mammogram’s informative value improves with age-related declines in breast density. The USPST recommendations are cost-effective population studies that must be used as one more piece of data available to physicians who must then make screening recommendations for the individual patient. 

, PhD, FACS is an associate professor with the Division of Surgical Oncology, Department of Surgery, and an attending surgeon at the Olson Women’s Center at the University of Nebraska Medical Center in Omaha. He is also a member of the editorial advisory board for 

CT Scans Increase Patients’ Risk of Cancer 

Imaging specialists with the University of California in San Francisco (UCSF) say routine computed tomography (CT) scanning is associated with a 1 in 80 chance of developing cancer in certain groups. According to the investigators, radiation doses from CT scanning are higher than previously thought and vary between procedures. 

“In day-to-day clinical practice, we found signifi- cant variation in the radiation doses for the same type of CT procedures within institutions and across institutions,” said lead investigator Rebecca Smith- Bindman, MD, professor of radiology at UCSF. 

According to the researchers, approximately 70 million CT procedures are performed annually, up from 3 million in 1980. The process is typically much faster than it used to be, but Dr Smith- Bindman described this as a “double-edged sword.” She explained, “Because the images can be obtained so quickly, it has been very tempting to do multiphase studies...increas[ing] the radiation dose.” 

The UCSF team looked at the 11 most frequently ordered CT procedures and assessed radiation exposure associated with each. Then they calculated the potential risk of cancer related to each procedure. The review involved 1119 patients treated at four institutions in the San Francisco Bay Area in a 5-month period. All the procedures involved the head and neck, chest, or abdomen and pelvis. 

They measured a mean 13-fold variation between the lowest and highest radiation doses delivered with one CT procedure. The number of CT scans required to cause cancer was greater for women than for men, which Dr Smith- Bindman said was what the investigators had expected. Age was also a factor. 

The estimated cancer incidence for women was 1 in 270 for a CT coronary angiogram at age 40 years; in men, the same procedure was associated with an estimated 1 in 600 incidence. CT scans of the head were associated with far lower rates of cancer, at 1 in 8100 for 40-year-old women and 1 in 11,080 for men of the same age. Patients less than age 20, however, had nearly double the risk. “The risk associated with obtaining a CT is routinely quoted as around 1 in 1000 patients who undergo CT will get cancer,” Dr Smith-Bindman said. “In our study, the risk of getting cancer in certain groups of patients for certain kinds of scans was as high as 1 in 80.” 

The dose of radiation delivered with a single CT scan was as high as 74 mammograms or 442 chest radiographs. To minimize patients’ exposure, the investigators recommended reducing unnecessary studies or those not likely to affect clinical decision-making. They suggested standardization for CT scanners regarding low-dose and lower-dose protocols and the adoption of federal standards for radiation doses across patients and facilities, as well as FDA oversight on the performance of CT scans. The study was published in the 

Medroxyprogesterone Decreases Hot Flushes in Prostate Cancer 

Researchers from University Hospital in Poitiers, France, published a study online at the 

 Website that says medroxyprogesterone helps reduce hot flushes in men receiving androgen suppression for prostate cancer. 

In a double-blind trial, 919 men were treated for 6 months with 11.25 mg of leuprorelin, an androgen suppressor, for prostate cancer. In the sixth month, the 311 men who requested treatment for hot flushes or reported experiencing 14 or more hot flushes during the preceding week were randomized to receive daily treatment with 75 mg of venlafaxine (n = 102), 20 mg of medroxyprogesterone acetate (n = 108), or 100 mg of cyproterone acetate (n = 101). 

To assess the number of hot flushes, patients were asked to record them in a diary for 1 week before randomization. They also completed a quality-of-life questionnaire before each visit. Data were compared to baseline evaluations and assessments at 4 weeks, 8 weeks, and 12 weeks post-randomization. Patients who received at least 1 dose of the study treatment were included in the efficacy analysis; 2 patients were excluded from the efficacy analysis for deviating from protocol. 

Investigators reported a 47% drop in median daily hot flushes 1 month after randomization. Cyproterone and medroxyprogesterone were associated with significantly larger declines in the incidence of hot flushes compared with venlafaxine (P <.001). There was no significant difference in the occurrence of hot flushes between the cyproterone and medroxyprogesterone groups, but the authors noted that “cyproterone is a recognized treatment in prostate cancer and its use could interfere with hormonal therapy.” Thus, they suggested medroxyprogesterone be considered as a “standard treatment for men undergoing androgen suppression for prostate cancer.” 

Five patients in the medroxyprogesterone group experienced serious adverse effects compared with 4 in the venlafaxine group and 7 in the cyproterone group. They noted that the short follow-up in the study and the potential effect of steroidal antiandrogens on prostate cancer were limitations to this study. 

FDA Weighs Erlotinib as Maintenance Therapy in NSCLC 

The FDA has decided to convene a panel of outside experts to assess the effectiveness of erlotinib (Tarceva) as a maintenance therapy for patients with non—small cell lung cancer (NSCLC) compared with currently available treatments. In an FDA review, regulators agreed that erlotinib, manufactured by OSI Pharmaceuticals, slows lung cancer progression and prolongs survival when used after chemotherapy. 

OSI has petitioned the FDA to approve erlotinib as a maintenance therapy or to stop the spread of cancer in patients who are responsive to their chemotherapy regimen. It is currently approved as a second-line treatment for progressive NSCLC following chemotherapy. 

The FDA reviewed data from a study of 889 patients who started erlotinib or placebo immediately after chemotherapy. Those taking erlotinib experienced stable disease for at least 3 months. This was a 1-month improvement compared with the patients who received placebo. 

According to the FDA, “The main issue concerns other available treatment options,” such as pemetrexed (Alimta), which was approved earlier this year as maintenance therapy for NSCLC; and docetaxel (Taxotere), which has been shown to improve survival in lung cancer by 3 months when treatment is initiated after signs of progression following stable disease on chemotherapy. Erlotinib has also demonstrated similar efficacy when initiated after disease has resumed progression, which means overall survival (OS) appears to be longer with delayed erlotinib than with immediate erlotinib. 

The FDA also said that patients with EGFR-negative tumors had poorer OS rates in the erlotinib arm. The reviewers said this might be a consideration in any approval decision. In addition, erlotinib was less effective in patients with squamous histology. 

The Duke Clinical Research Institute published data from a study that found patients with a new cancer diagnosis have problems sleeping. Kevin Weinfurt, PhD, associate professor in the departments of psychiatry and behavioral sciences and psychology and neuroscience at Duke said, “Our study found that when it comes to overall impact upon quality of life, sleep disruption is highly significant.” According to the investigators, earlier studies suggest that nearly half of all people with cancer report sleep disruption and that the problem often persists after treatment has concluded. 

Dr Weinfurt and colleagues mailed invitations to patients listed in the University’s tumor registry, inviting them to participate in focus groups. The study included 10 focus groups with 6 to 12 participants in each one. Seven groups included only patients in active treatment; the remaining 3 comprised patients who had finished treatment. 

Many patients considered sleep disruption to be a major problem. Notable causes included hot flashes and night sweats. Others had difficulty finding a comfortable sleeping position due to tenderness from a surgical site, radiation burns, or medical devices (eg, ports, tubing, or ostomy). Anxiety was another factor. 

The investigators said some of the treatments for cancer, including hormonal therapies and chemotherapy, have side effects associated with insomnia and fatigue. Being immunocompromised is also related to insomnia. The patients said lack of sleep at night contributed to daytime tiredness and difficulty with concentration. The researchers concluded by saying there is not enough evidence to “guide the management of insomnia in patients with cancer,” and they recommended more attention be devoted to this issue. Results were published in 

Advanced Care Planning Associated with More Practical Coping Skills in

Advanced care planning has become something of a controversial issue. Opponents of healthcare insurance reform have misbranded end-of-life discussions as “death panels.” The Catholic Church recently weighed in, with the U.S. Conference of Bishops ruling that Catholic hospitals should ignore advanced care directives that refuse medically assisted nutrition and hydration for patients who are not “imminently dying.” Some medical and psychological experts oppose advanced care planning out of concerns that discussing death will increase stress levels in patients with a terminal illness. A study presented at the 51st ASH Annual Meeting, however, found that patients with hematologic malignancies who participate in advanced care planning are no more likely to have psychosocial problems than their counterparts who lack an advanced care plan. 

Only 10% of Americans have an advanced care plan, a document that address end-of-life choices and typically includes a living will and designates a healthcare proxy (the person authorized to make healthcare choices for the patient should he or she become incapacitated). An advanced care plan might describe the patient’s wishes regarding resuscitation or other life-sustaining measures. 

According to researchers from the University of Nebraska Medical Center in Omaha and Fred Hutchinson Cancer Research Center in Seattle, previous studies suggest only 50% of patients with a hematologic cancer create an advanced care plan prior to a high-risk procedure like stem cell transplantation. Earlier data also show that those most likely to die are least likely to have a plan in place. 

Researchers analyzed data for 293 patients with blood cancers in the HEMA-COMM (Hematology Communications) study, which evaluated communication between physicians and their patients. Patients were considered to have an advanced care plan if they had a living will and a designated healthcare proxy; those lacking one or both of these provisions were considered not to have an advanced care plan. Based on self-reporting, 149 (51%) were found to have an advanced care plan. Patients with advanced care plans tended to be older (a median of 56 years vs 52 years for those without plans) and have higher incomes. They were more likely to have a leukemia or myelodysplastic syndrome diagnosis and to have undergone prior cancer treatment. 

In addition to comparing the psychosocial wellbeing (ie, coping, depression/anxiety, denial, social support, and quality of life) of patients with and without advanced care plans, the retrospective study also sought to uncover ways to encourage patients to engage in advanced care planning. Depression and anxiety were measured with the Hospital Anxiety and Depression Scale (HADS), coping was assessed with the BRIEF-COPE scale, social support was evaluated using the MOS-SS scale, and quality of life was assessed with the MOS-SF36 scale. Researchers also looked at denial. 

Psychosocial wellbeing was found to be relatively equal between the two groups, except for coping. Patients that had advanced care plans were more likely to practice problem-focused coping methods, such as taking advice, seeking moral support from or talking about their feelings with others, maintaining a positive outlook, and actively working to address the problem. The authors defined “problem-focused coping” as actions taken to alter the source of stress, which they said “predominates when a person feels that something constructive can be done to affect the outcome of events.” Patients without advanced care plans often resorted to emotion-focused coping patterns, including denial, behavioral or mental disengagement, turning to religion, self-blame, and substance abuse. 

Based on estimates of life expectancy and cure rates from their physicians, patients anticipated to have a worse prognosis were more likely to have an advanced care plan and discuss end-of-life wishes with a physician. Nearly one-third (30%) of those with a plan discussed their end-of-life wishes with a physician, 62% discussed wishes for life support use with family, and 8% did not discuss their wishes with anyone. 

The researchers concluded that patients with problem-focused coping patterns were more likely to engage in advanced care planning, possibly reflecting a “realistic or pragmatic view of clinical outcomes.” They may be more likely to recognize the need for an advanced care plan because of an unfavorable prognosis. 

Lead author Fausto R. Loberiza Jr, MD, associate professor at the University of Nebraska Medical Center, said he believes this practicality may be one avenue for increasing patient participation in advanced care planning. In a press release, Dr Loberiza said, “In order to increase engagement in advanced care planning, it is important to focus on the practical importance of advanced care planning regardless of prognosis, and deemphasize the emotional aspects of advanced care planning.” He suggested such an approach might be more appealing to patients “regardless of coping style.” He added that advanced care planning is important for all individuals. “We hope that more people engage in this important process,” he concluded.

A selection of essays and articles that discusses such issues as breast cancer screening recommendations, the oncologist's role in how mass media reports about cancer, patients' increased risk of cancer from CT scans, insomnia in cancer patients, and the association of advanced care planning with more practical coping skills in patients with hematologic malignancies.


News & Opinion

The National Cancer Institute, in collaboration with the CDC and the American Cancer Society, recently reported that fewer men and women are dying from cancer each year in the United States. According to the report, cancer rates have declined more than 18% in men and 11% in women since the early 1990s, largely because of reductions in the death rates for lung, prostate, and colon cancer in men; and colon and breast cancer in women. 

No one would argue that this is not welcome news. At the same time, it is widely acknowledged that we are a long way from curing or preventing most cancers. Recently on National Public Radio (NPR), Dr John Marshall, director of the Ruesch Center for the Cure of Gastrointestinal Cancers at the Lombardi Comprehensive Cancer Center at Georgetown University, asked a good question: Why aren’t we more upset about it? 

Dr Marshall pointed out that AIDS only came to national attention in the late 1980s, but advocacy groups sprang up immediately to demand more funding for HIV/AIDS research. In addition, enrolling in a clinical trial is almost de rigueur for people with HIV/AIDS. Dr Marshall also noted that 60% to 70% of children with cancer are enrolled in clinical trials by their parents. This has resulted in a much faster rate of progress against pediatric cancers as compared with progress in treating cancers in adults. If parents are willing to enroll their children in trials, why is the rate of clinical trial participation for adults with cancer a paltry 5% to 10%? 

It almost seems like society has become largely desensitized to the steady drip of adult cancer deaths, and too few consider finding new and better treatments an urgent imperative—until they or a loved one receives a cancer diagnosis. While there has been progress against certain types of cancer, our ability to cure people remains hampered by a lack of understanding of the etiology and biology of the vast majority of neoplasms, as well as a shortage of eff ective treatments. We need to counteract the relative indiff erence by proactively lobbying for more funding to increase bench research and encourage patients to participate in clinical trials by emphasizing the benefits for both themselves and for posterity. 

In October, President Obama declared H1N1 a national emergency. The CDC had reported that as many as 6000 Americans died from H1N1 between April and October 2009. Over that same period, more than 270,000 people died of cancer, based on the American Cancer Society’s estimate of 1500 cancer deaths per day in the United States in 2009. As every plumber knows, a steady drip adds up to a lot of water and should never be ignored: one faucet dripping 30 times a minute wastes 2 gallons of water per day or 1041 gallons per year. We need to work harder to convince the country that, with more than 11 million people in this country living with cancer in a given year, it is a national emergency. 

The National Cancer Institute, in collaboration with the CDC and the American Cancer Society, recently reported that fewer men and women are dying from cancer each year in the United States.

December 2009 | Oncology & Biotech News