Sunitinib Linked to Heart Failure and Hypertension

Patients taking sunitinib (Sutent) should be monitored for cardiovascular side effects such as hypertension and signs of heart failure, especially those patients with a history of coronary artery disease or cardiac risk factors, a team of oncologists and cardiologists said last month in The Lancet. The recommendation is based on evidence of cardiac side effects among some patients taking sunitinib to treat gastrointestinal stromal tumors (GIST). Sunitinib is approved to treat advanced renal cell carcinoma and metastatic GIST after resistance to imatinib (Gleevec) develops.

Dr. Ming Hui Chen of Harvard Medical School and her colleagues retrospectively analyzed the medical records of 75 GIST patients treated at the Dana-Farber Cancer Institute during a phase I/II study. A total of 11 percent of patients had a cardiovascular event - two patients had heart attacks and six others experienced heart failure. In addition, 47 percent of patients developed hypertension - systolic and diastolic blood pressure increased during the first cycle of treatment - and 20 percent had reduced heart function.

Most cardiac problems including hypertension were manageable and the majority of patients with heart failure resumed sunitinib therapy. Histories of coronary artery disease and/or hypertension were predictors of cardiovascular events.

Cardiac side effects have been reported for other successful targeted cancer drugs such as trastuzumab (Herceptin) and bevacizumab (Avastin). The study supports a growing view that oncologists and cardiologists need to work together to identify the cardiac side effects of new, targeted drugs and to manage cardiac health throughout therapy.

"The paradigm remains to treat the cancer while caring for the heart," said Dr. Chen, a cardiologist who specializes in the cardiac health of adult cancer patients. She noted that although the cardiotoxicity in this study was not seen in phase III trials, the patients may be more similar to patients in the general population now being treated with sunitinib.

A letter in the January 3 New England Journal of Medicine reports on 14 patients with metastatic renal cell carcinoma who also experienced rapid, marked increases in blood pressure during treatment with sunitinib. The effect was revealed by home blood-pressure monitoring and had been missed during routine office visits.

"Our study suggests that rapid and large increases in blood pressure should be anticipated in patients who are treated with sunitinib," conclude the authors from Hôpital Européen Georges Pompidou in Paris.

Cancer Doctors May Need Training on Empathy Skills

Cancer specialists (oncologists) may need additional training to encourage patients to express their concerns and negative emotions and to respond empathically to these concerns, researchers recommended in a study published December 20, 2007, in the Journal of Clinical Oncology.

The report presented data from the Studying Communication in Oncologist-Patient Encounters (SCOPE) project, an NCI-funded, three-site study from Duke University, the Durham Veterans Affairs Medical Center, and the University of Pittsburgh. It is based on results from 398 clinic conversations between 51 oncologists and 270 patients with advanced cancer. The study found that the oncologists encountered few empathic opportunities during their patient meetings (37 percent of visits) and responded with empathic statements infrequently (only 22 percent of the time).

Empathic responses are important in cancer care because "patients have less anxiety and depression and report greater satisfaction and adherence to therapy," the researchers noted. The study found that female patients were more likely to disclose painful emotions to female oncologists. In addition, younger oncologists and those who rated their orientation as more socioemotional than technical were more likely to respond with empathic statements.

"Oncologists and patients need to work to create an alliance conducive to patients expressing their emotions," the researchers suggested. Although the oncologists expressed high levels of confidence in addressing emotions, they may need more training to recognize emotions and to learn how to respond to patient concerns. "Many empathic opportunities were indirect and patients may be more satisfied if they can learn how to express their emotions more directly so that oncologists can respond appropriately," the authors noted.

Biomarkers Linked to DCIS Outcomes

Ductal carcinoma in situ (DCIS), where abnormal cells are found in the lining of a breast duct, is usually treated with surgical lumpectomy, followed by radiation, chemotherapy, a combination of the two, or surveillance. Most women undergoing these treatments will not experience a recurrence, but in 15 to 30 percent of women, a new tumor will develop within 10 years, and about half of these will be invasive breast cancers. To help clinicians determine whether DCIS is likely or unlikely to follow this course, researchers at the University of California, San Francisco, and the Bay Area Breast Cancer Specialized Program of Research Excellence (SPORE) have identified biomarkers associated with invasiveness. Their results appear in the November 12, 2007, Cancer Cell.

Using lumpectomy samples from 70 women who were diagnosed with DCIS and then followed for more than 10 years (180 months), the researchers looked at several markers associated with stress-induced senescence or proliferation. They compared the profiles of these markers in women whose DCIS did not progress to those in women for whom the DCIS did progress.

The results showed that in samples containing proliferating cells identified using Ki67 proliferation marker, overexpression of stress-activated p16 and/or COX-2 proteins reflects abnormal response to cellular stress and predicts subsequent tumor events within the first decade after the initial DCIS diagnosis. Low expression of Ki67 (regardless of the p16 and COX-2 status) usually indicates favorable prognosis. Other findings include observation of post-transcriptional rather than transcriptional regulation of COX-2 expression in a subset of HER-2-positive tumors.

The authors conclude that when tissue shows stress activation and deregulation of p16 and Rb signaling, this "may represent a defining signature of basal-like carcinogenesis that can be assayed [before] the development of invasive disease," with opportunities for prevention years before an invasive tumor actually occurs.

Older Breast Cancer Survivors Less Likely to Adhere to Follow-Up

Two new studies have revealed that older breast cancer patients who are more likely to experience recurrence are less likely to undergo recommended follow-up mammography and adhere to prescribed medications. In the clinical trials that lead to treatment and follow-up guidelines for breast cancer, older women are usually underrepresented due to eligibility criteria or comorbid conditions. But two recent community-based studies that focused on breast cancer survivors over the age of 65 addressed specific questions related to the behavior and outcomes of this group, using participants in health systems that collaborate through the NCI-funded HMO Cancer Research Network (CRN).

The first study, published online December 1, 2007, in the Journal of General Internal Medicine, looked at surveillance mammography among women who were diagnosed with stage 2 or earlier breast cancer. Most of the 1,762 women in the study were older than 70. After 4 years of follow-up, the study showed that women at the highest risk of recurrence - those who were diagnosed at stage 2 and those who had breast-conserving surgery without radiation - were the least likely to have recommended mammograms. Other factors associated with this trend included age older than 80 and nonwhite ethnicity.

The second study, published ahead of print in the Journal of Clinical Oncology on December 10, 2007, reviewed tamoxifen use by 961 women during a 5-year follow-up period after treatment. The results showed that 49 percent of these women stopped taking tamoxifen within this time. Women over the age of 75, as well as those who had comorbid conditions, breast-conserving surgery without radiotherapy, and those in whom tumor estrogen-receptor status was unknown, were the most likely to discontinue use. Reasons for stopping in the first year most often related to side effects of the drug.

In both papers, the authors noted that by understanding the risk of nonadherence to recommended follow-up procedures, clinicians may be able to tailor their care of this patient group.

More information on collaborative research opportunities and NCI's CRN resource can be found at http://crn.cancer.gov/about/work.html.

Trial Shows Some Benefit of Adjuvant Chemo for Early Colorectal Cancer

A large European trial designed to determine the value of adjuvant chemotherapy after surgery for stage II colorectal cancer has found that patients receive "small but definite benefit" in both survival and risk of recurrence, say researchers at the University of Birmingham in England.

The QUick And Simple And Reliable (QUASAR) Trial Collaborative Group, led by Dr. Richard Gray, reported results on 3,239 patients after 5.5 years median follow-up in the December 15, 2007, Lancet. Compared with observation alone, patients receiving chemotherapy had an 18-percent reduction in risk of death, which, in a population whose mortality rate is about 20 percent, conferred an absolute reduction of 3.6 percent at 5 years. The 22-percent reduction in risk of recurrence occurred almost completely in the first 2 years, and then leveled off.

"Chemotherapy seems to prevent a proportion of recurrences and deaths rather than just delaying them," wrote the authors, "which makes the life-years gained more substantial, especially for younger patients."

Drs. David Cunningham and Naureen Starling of the Royal Marsden Hospital in Surrey wrote in an editorial that the QUASAR results do not fully resolve all of the issues in this population, and that "identification of patients most likely to benefit from therapy remains important." Subgroup analyses are underway.

Better information about these groups, they wrote, may help patients and physicians assess the risk/benefit ratio among the three options currently in use: fluorouracil with oxaliplatin, fluoropyrimidine, or observation. These newer drugs and combinations have largely supplanted the drugs tested in QUASAR.