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Sept. 1 Issue Transcript

Issue 17 of the Journal of the National Cancer Institute includes a commentary on the use of combination versus sequential chemotherapy in metastatic breast cancer and a study and accompanying editorial on the cost-effectiveness of cetuximab in metastatic colorectal cancer. This issue also includes research on an antibody that showed anticancer activity in ovarian cancer cell lines and a study and accompanying editorial on the overestimation of the benefits of cancer screening. In the last study, researchers evaluated whether non-skin cancer was independently associated with vulnerability and frailty in older people.

Considering Combination versus Sequential Chemotherapy in Metastatic Breast Cancer

Both combination and sequential single-agent chemotherapy are reasonable options to treat metastatic breast cancer, but the choice between the two should ultimately be based on patient- and disease-related factors, according to a commentary published online August 5

Whether to use several chemotherapy drugs simultaneously or single agents sequentially, one after the other, is a controversial issue. To explore this question, the European School of Oncology Metastatic Breast Cancer Task Force held an open debate on the relative benefits of combination versus sequential therapy at the 6th European Breast Cancer Conference.

Fatima Cardoso, of the Jules Bordet Institute in Brussels, and colleagues summarize the recommendations of that task force, which includes the use of sequential chemotherapy with a single agent for patients with advanced metastatic breast cancer without rapid progression or life-threatening metastasis, and for those who do not need rapid symptom or disease control.

The authors do not take one side over the other. Instead, they discuss the contributions and caveats of existing data on the two therapies. They do, however, note that because metastatic breast cancer is incurable, quality of life and overall survival should be the endpoints against which any systemic therapy is evaluated.

Cost-Effectiveness of Cetuximab in Metastatic Colorectal Cancer

From a health-care system perspective, it may be more efficient to use the drug cetuximab only in colorectal cancer patients whose tumors have a wild-type KRAS gene, according to a study published online August 7.

Earlier, patients whose tumors harbored wild-type KRAS were found to have a higher survival advantage when treated with cetuximab in a randomized trial by the National Cancer Institute of Canada Clinical Trials Group.

Nicole Mittmann, of the HOPE Research Centre Sunnybrook Health Sciences Centre, in Toronto, and colleagues used prospectively collected resource utilization and health utility data from that trial to conduct a cost-effectiveness analysis to determine the costs per life-year gained and costs per quality-adjusted life-year gained.

Mean survival times for the study arms were calculated over an 18- to 19-month period for all patients in the study and for patients whose tumors had wild-type KRAS.

For all patients, cetuximab showed very high incremental cost-effectiveness ratios—meaning it was very costly in relation benefits—compared with best supportive care. The incremental cost-effectiveness ratios were, however, more favorable for patients whose tumors harbored wild-type KRAS.

In an accompanying editorial, Robin Yabroff, of the Division of Cancer Control and Population Science, National Cancer Institute in Bethesda, Md., and Deborah Schrag, of the Dana

Antibody Linked to Chemotherapy Drug Inhibits Ovarian Cancer in Lab

A novel anticancer agent, consisting of a monoclonal antibody linked to a chemotherapy drug, showed substantial antitumor activity in ovarian cancer cell lines and in mice, according to a study published online July 29.

The agent, known as an immunoconjugate, targets a protein, EphA2, which is overexpressed in many human cancers but is absent or expressed at low levels in normal tissues.

Anil K. Sood, of The University of Texas M.D. Anderson Cancer Center in Houston, and colleagues tested the immunoconjugate in ovarian cancer cell lines, where it bound to cells with high levels of EphA2 but not to those without the protein. In mice, the EphA2 immunoconjugate inhibited tumor growth by 85%–98% compared with that in mice treated with a control immunoconjugate, a highly statistically significant difference. In cell lines, its antitumor effects were also statistically significantly related to decreased proliferation and increased apoptosis of tumor cells.

Chemotherapy drugs typically affect both tumor and normal tissues, which can result in side effects. The immunoconjugate tested in this study allows for highly selective delivery of chemotherapy.

The Public Overestimates Benefits of Cancer Screening, Survey Finds

A public survey conducted in Europe found that the vast majority of people overestimate the life-saving benefits of breast and prostate cancer screening, according to a new study published online August 11.

Gerd Gigerenzer, of the Max Planck Institute for Human Development in Berlin, and colleagues conducted a survey of over 10,200 people from nine European countries to assess perceptions of cancer-specific mortality reduction associated with mammography and prostate-specific antigen screening, and to determine the sources of information they rely on.

The authors found that the majority of participants have a dramatic overestimation of the benefits of such tests, and that doctors and other sources of information appear to have little impact on improving knowledge of the level of benefit. Ninety-two percent of women overestimated the benefit of mammography screening by at least one order of magnitude or reported they did not know; 89% of men overestimated the benefit of prostate-specific antigen screening or did not know.

In an accompanying editorial, Lisa M. Schwartz, and Steven Woloshin, of the Dartmouth Institute for Health Policy & Clinical Practice in Hanover, N.H., point out that accurate screening messages should be more prominent and include risks associated with overdiagnosis and overtreatment.

The editorialists call some of the researchers’ methods biased toward overe

Older Cancer Patients Have More Frailty Than Other Seniors

Older people with a history of cancer are more likely to have disabilities and be frail and vulnerable than older adults who have not had cancer, according to a study published online July 29.

The prevalence of frailty and vulnerability among older cancer patients will pose an increasing challenge for physicians as the population ages. By the year 2030, persons who are older than 65 years are projected to make up 70% of cancer patients and have 65% of cancer deaths.

Supriya Gupta Mohile., from the James P. Wilmot Cancer Center at the University of Rochester in N.Y., and colleagues used data in the 2003 Medicare Current Beneficiary Survey to evaluate whether non-skin cancer was independently associated with vulnerability and frailty. They found that survey respondents with a history of non-skin cancer had statistically significantly more limitations in the activities of daily living and other measures of frailty and vulnerability than those who had not had cancer.
The authors conclude that their study “establishes the increased baseline prevalence of factors among cancer patients that have been associated with adverse health outcomes…” They also note that the study is “a first step in highlighting the importance of “staging the aging” among cancer patients by the use of geriatric assessment.”