Gemcitabine after Pancreatic Cancer Surgery Improves Survival

Patients who received the chemotherapy drug gemcitabine after surgery for pancreatic cancer lived 2 months longer than patients who had surgery alone, according to the final results of a large, randomized clinical trial presented at the ASCO annual meeting last week.

Less than 20 percent of patients with pancreatic cancer are candidates for surgery, because the disease is often detected in the late stages. Gemcitabine has been a standard treatment for patients with advanced (and inoperable) pancreatic cancer for a decade. The new findings support use of the drug in the adjuvant setting.

"We have shown that this treatment more than doubles the overall survival 5 years after treatment," said Dr. Helmut Oettle of the Charité School of Medicine in Berlin, Germany, who presented the results.

The study included 368 patients who underwent surgery followed by 6 months of adjuvant gemcitabine treatment or surgery alone. In the gemcitabine group, 21 percent were alive at 5 years compared with 9 percent in the control group. Median survival in the gemcitabine group was 22.8 months compared with 20.2 months in the control group.

Preliminary results from the trial were reported at ASCO in 2005 and showed that post-surgery gemcitabine could delay a recurrence of the disease. These findings led to an increase in the use of the drug in the United States and Europe, according to the researchers.

"We can now say that giving this agent after surgery to patients with early stage disease will improve a patient's survival," commented Dr. Nicholas Petrelli of the Helen F. Graham Cancer Center at the meeting. "We couldn't say that before."

Cetuximab Plus Chemotherapy Extends Survival for Advanced Lung Cancer

Patients with advanced non-small-cell lung cancer (NSCLC) who received cetuximab (Erbitux) plus chemotherapy lived on average 5 weeks longer than patients who received chemotherapy alone, according to results reported at the ASCO annual meeting.

In the phase III FLEX trial, 1,125 patients with all types of NSCLC were randomly assigned to receive standard platinum-based chemotherapy alone or chemotherapy plus cetuximab. Nearly all of the patients had stage IV disease. Overall survival was higher for those who received cetuximab plus chemotherapy (11.3 months) compared with those who received chemotherapy alone (10.1 months).

The benefit of the combination therapy was seen in patients with all histological subtypes of NSCLC, including adenocarcinoma and squamous cell carcinoma, the two most common subtypes. The main side effect was an acne-like skin rash that could be managed.

"Patients with advanced NSCLC have limited treatment options and life expectancy is short, so the survival increase shown in this study is an important step for these patients," noted Dr. Robert Pirker, an associate professor of medicine at the Medical University of Vienna in Austria and the study's lead author.

The only other final-stage randomized trial to show a survival benefit in lung cancer was a 2005 study of bevacizumab (Avastin) plus chemotherapy. Unlike the current study, that trial did not include patients with squamous cell carcinoma.

Dr. Thomas Lynch of Massachusetts General Hospital, who commented on the findings at ASCO, said the study was well done and produced "a clinically meaningful benefit for a large population."

Zoledronic Acid Improves Early Breast Cancer Treatment

The addition of zoledronic acid (Zometa) to adjuvant endocrine therapy in premenopausal women with early stage breast cancer significantly improves clinical outcomes beyond those achieved with endocrine therapy alone, researchers reported at the ASCO annual meeting. The results are from a phase III randomized trial of 1,800 women conducted by the Austrian Breast and Colorectal Cancer Study Group.

Zoledronic acid, part of a class of drugs known as bisphosphonates, is already used to treat bone metastases, and this trial was conducted based on data from preclinical and early phase trials indicating that the drug can also shrink tumors and block metastatic activity. The results bear this out, said principal investigator Dr. Michael Gnant from the Medical University of Vienna.

Overall, the trial showed no difference in disease-free survival between women treated with tamoxifen or anastrozole. But the addition of zoledronic acid to either therapy decreased the risk of a disease-free survival event by 36 percent compared with hormone therapy alone, Dr. Gnant said. At a median follow-up of 60 months, overall disease-free survival was 92.4% and overall survival was 97.7%.

Women in the trial - all of whom were premenopausal with stage I or II breast cancer that was responsive to endocrine therapy - were treated with surgery and, if needed, radiation therapy. They also received the drug goserelin to temporarily suppress the function of the ovaries. Each was randomly assigned to one of four adjuvant therapy arms: tamoxifen alone, the aromatase inhibitor anastrozole alone, or either drug plus zoledronic acid. Treatment lasted 3 years.

The drug was also well tolerated, with no indication of increased risk of liver problems or damage to the jaw bone - two side effects which have been associated with higher doses of bisphosphonate drugs.

Acupuncture Tested in Cancer Patients after Neck Surgery

For patients with head and neck cancers who undergo a surgical procedure known as neck dissection, acupuncture may help reduce pain and improve functioning afterward, according to preliminary findings from a randomized trial presented as a poster at ASCO.

"Acupuncture appears to be a promising treatment for these patients, and more research is warranted," said Dr. David Pfister of Memorial Sloan-Kettering Cancer Center, who discussed the results at ASCO. Conventional treatments have limited success in helping patients following neck dissections, he noted, and "there is plenty of room for improvement."

The study included 34 patients who received acupuncture and 36 who received standard care with pain medication and physical therapy. In the experimental group, four sessions of acupuncture were administered over the course of a month. A standard set of acupuncture points was used for each patient, and more specialized points were selected depending on the pain for each individual.

Thirty-nine percent of the patients who received acupuncture had significant improvements in pain and function, compared with only 7 percent who experienced improvement in the standard care group, according to assessments using a measure called the Constant-Murley scale. Some patients in the acupuncture group had significant relief of dry mouth, while no relief was observed in the patients receiving standard care.

Future studies may include a group that receives "sham" acupuncture to control for the placebo effect.

Protein Biomarkers Point to Early Stage Pancreatic Cancer

Researchers have discovered proteins in blood that reliably indicate early stage pancreatic cancer, according to a report June 10 in PLoS Medicine. Although more research is needed before an actual diagnostic test could be developed, the study's lead author, Dr. Samir Hanash from the Fred Hutchinson Cancer Research Center, said the study represents a "breakthrough in the application of advanced proteomic technologies and mouse models to cancer-biomarker discovery."

The mouse model used in the study was genetically engineered to mimic the course of pancreatic cancer in humans, from development of precancerous lesions through advanced disease. Using proteomic technologies, the researchers identified a panel of five proteins - LCN2, REG1A, REG3, TIMP1, and IGFBP4 - consistently found in mice with precancerous growths called pancreatic intraepithelial neoplasia, but not in mice with full-blown cancer or healthy control mice.

To validate the five-protein panel, they tested it against blood samples from 13 people in an unrelated cancer prevention study who developed pancreatic cancer within a year of donating the sample. The researchers were "blinded" to which samples came from cancer patients and controls. The five-protein panel consistently identified samples from the patients who developed cancer, and when it was combined with another protein marker, CA19.9, which is elevated in up to 80 percent of newly diagnosed pancreatic cancer patients, the test was even more accurate.

The next steps include studies to validate the biomarker panel's performance in distinguishing between pancreatitis (inflammation of the pancreas) and pancreatic cancer - under the auspices of NCI's Early Detection Research Network (which also partly funded this current study, along with NCI's Mouse Models of Human Cancers Consortium) - and continued studies to assess its value in early detection among those at high risk of pancreatic cancer.

Initial Costs of Cancer Treatment on the Rise

In the first study to examine trends in the costs of specific components of initial cancer care in the United States, investigators found that Medicare payments for initial treatment rose significantly for breast, colorectal, and lung cancer patients but dropped slightly for prostate cancer patients between 1991 and 2002. These results, published online June 10 in the Journal of the National Cancer Institute, highlight the financial challenges to Medicare posed by the rising number of cancer patients in the United States as the population ages, the study authors said.

The investigators used the linked Surveillance, Epidemiology, and End Results-Medicare data from 306,709 newly diagnosed breast, colorectal, lung, and prostate cancer patients age 65 or older. Specific services evaluated included cancer-related surgery, chemotherapy, radiation therapy, and hospitalizations during the initial treatment period (defined as from 2 months prior to 12 months following diagnosis). The investigators assessed the proportion of patients who were hospitalized, received cancer-related surgery, chemotherapy, and radiation therapy, as well as the average cost per patient for those services.

After adjusting for inflation, the investigators found that between 1991 and 2002 the average cost per patient rose $7,139, $5,345, and $4,189 for lung, colorectal, and breast cancer, respectively. Prostate cancer costs decreased by $196, due to a decline in the use of radical prostatectomy. The most significant increases were due to the percentage of breast, lung, and colorectal cancer patients receiving chemotherapy and the average cost per patient for chemotherapy. Over this time period the proportion of breast and prostate cancer patients receiving radiation therapy increased, as did the cost of radiation therapy. However, hospitalizations during the initial treatment period accounted for the greatest portion of total Medicare payments.

The study ended before the introduction of new, more expensive chemotherapies and targeted therapies such as erlotinib and bevacizumab, noted the authors. "Evaluation of the impact of these new agents on total Medicare expenditures for initial cancer care will be a priority for future research," said the lead author, Dr. Joan Warren from NCI's Division of Cancer Control and Population Sciences.