NCI Cancer Bulletin: A Trusted Source for Cancer Research NewsNCI Cancer Bulletin: A Trusted Source for Cancer Research News
May 17, 2005 • Volume 2 / Number 20 E-Mail This Document  |  Download PDF  |  Bulletin Archive/Search  |  Subscribe

The information and links on this page are no longer being updated and are provided for reference purposes only.

Cancer Research HighlightsCancer Research Highlights

Drug Reduces Transfusions for Some with Bone Marrow Disorder

A clinical trial of the drug lenalidomide (Revlimid) for a bone marrow disorder has found that it helped a particular subgroup of patients avoid the blood transfusions used to treat the disease, according to preliminary results from a clinical trial presented at the ASCO annual meeting.

All 148 patients in the study had a form of myelodysplastic syndrome (MDS) and a genetic flaw - the deletion of DNA from chromosome 5, which occurs in 18 to 25 percent of cases. The study was launched after earlier results suggested that the chromosomal deletion may predispose patients to respond to lenalidomide.

After 24 weeks, 64 percent of the patients in the study no longer needed a transfusion. In addition, 70 percent of those who responded had fewer bone marrow cells with the chromosomal deletion, while the deletion was undetectable in 44 percent of responders. For the patients who responded, it took about a month to avoid dependence on blood transfusions. The study is ongoing, and after a median follow-up of 9 months, 91 percent of the responders continued to respond.

Dr. Alan List of the H. Lee Moffitt Cancer Center presented the findings. He noted that the deleted region on chromosome 5 may contain a tumor suppressor gene, though none has yet been found. His group will report further on that region in an upcoming publication.

Gastric Cancer Survival Improved with Neoadjuvant Chemo

Chemotherapy before and after surgery in patients with operable cancer of the stomach and lower esophagus significantly improved both progression-free and overall survival compared with surgery alone, British researchers reported this week at the ASCO annual meeting.

In the 503-patient, phase III trial, at 5 years, 36 percent of patients in the chemotherapy arm were still alive, compared with 23 percent of patients in the surgery-alone arm. In addition, 70 percent of patients given chemotherapy saw their disease progress during that time, compared with 83 percent of patients treated only with surgery. Recurrence of gastric cancer after surgery to remove tumors is fairly common, with the cancer recurring in up to 65 percent of patients.

"This approach should be considered one of the standard treatment options for patients with these cancers," said study leader Dr. David Cunningham of the Royal Marsden Hospital.

Downsizing the tumor prior to surgery, says Dr. Udai Kammula, a senior investigator in the NCI Center for Cancer Research (CCR) Surgery Branch, is one advantage the researchers hoped to achieve with neoadjuvant chemo. It also may mean that patients will be more likely to tolerate chemotherapy, because they aren't first weakened by major surgery. More patients in this trial, for example, were able to receive chemotherapy than those in a multicenter clinical trial conducted in the United States that reported a survival benefit associated with postoperative chemotherapy and radiation.

Regardless, Dr. Kammula states, "Although these findings are promising, they need to be validated in another large trial, particularly one that has improved preoperative staging with endoscopic ultrasound and laparoscopy and greater quality control with regard to surgery."

Low-Fat Diet May Lower Risk of Breast Cancer Recurrence

Significantly lowering dietary fat may lower the risk of recurrences of breast cancer in postmenopausal women treated for early-stage breast cancer, researchers reported at the ASCO annual meeting. The findings are from the NCI-sponsored Women's Intervention Nutrition Study, the first large-scale study to examine the influence of dietary fat on breast cancer outcomes in this population.

"This could be the first randomized controlled clinical trial of a lifestyle intervention that impacts breast cancer outcomes," said study lead author Dr. Rowan T. Chlebowski of the Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center.

The 5-year study included 2,437 women, aged 48 to 79, drawn from 37 U.S. centers. The study group was placed on a low-fat diet, averaging about 33 grams of fat daily, while a control group consumed a standard diet that included approximately 52 grams of fat per day. Each group had previously received similar treatments for early-stage breast cancer, including mastectomy or lumpectomy with radiation, and postsurgical treatment protocols, depending on whether patients had estrogen-dependent cancers.

After 5 years, women on the low-fat diet showed a significant reduction in cancer recurrence compared with the control group: 9.8 percent vs. 12.4 percent. Women on the low-fat diet who had been previously treated for nonestrogen-dependent cancer - which is typically associated with a greater likelihood of recurrence - had a 42-percent reduced risk of recurrence compared with those on a standard diet.

"The effect on ER-negative disease is a surprising and potentially important observation regarding breast cancer," said Dr. Peter Greenwald, director of NCI's Division of Cancer Prevention. "These data demonstrate the possible importance of considering dietary factors in cancer therapy trials."

Childhood Cancer Survivors Pay Heavy Health Toll as Adults, Study Finds

Data presented at the ASCO annual meeting show that survivors of childhood cancers are five times more likely to suffer from severe or life-threatening health problems than their healthy siblings. The data come from the Childhood Cancer Survivor Study (CCSS), a multi-institutional research project funded by NCI to investigate long-term morbidity and mortality associated with cancer treatment among survivors of pediatric cancers.

The study included 10,397 adults aged 18 to 48 who had been diagnosed with childhood cancer between 1970 and 1986 and had survived more than 5 years. The control group contained 3,304 healthy siblings ranging in age from 18 to 56. Some of the serious health problems seen among study participants included second malignant neoplasm (excluding nonmelanoma skin and thyroid cancer), heart attack, coronary artery bypass surgery, dialysis or kidney transplant, and mental retardation requiring special education. By age 45, such problems were observed in 37.4 percent of the childhood cancer survivors, compared with only 4.6 percent of the control group.

According to the study's lead author, Dr. Kevin C. Oeffinger of the University of Texas Southwestern Medical Center, 57.1 percent of cancer survivors reported moderate health problems by age 45, compared with 18.2 percent of their healthy siblings. Such moderate health problems included scars in the lungs that required oxygen therapy, congestive heart failure, blood clots in the head or lungs, cirrhosis of the liver, ovarian or testicular failure, and loss of an eye or even blindness.

"Although contemporary treatment regimens and technologies may have lessened some late effects associated with childhood cancer treatments, the acute and long-term side effects of cancer treatment remain significant for the growth and development of these children and for the health of the adults that they become," commented Dr. Barry Anderson, CCSS program director at NCI.

Treatments for Pancreatic Cancer Show Some Benefit

Two studies presented at the 2005 ASCO annual meeting offered potentially promising news for the treatment of pancreatic cancer, a highly fatal cancer for which there are few effective new treatments.

In the first study, German researchers reported that in patients with operable pancreatic cancer, a 6-month regimen of the chemotherapy drug gemcitabine (Gemzar) following surgery nearly doubled the duration of disease-free survival compared with surgery alone. Gemcitabine has been used for nearly a decade to treat patients with inoperable pancreatic cancer.

The study involved 356 patients with operable pancreatic cancer randomized either to 6 months of gemcitabine treatment within 6 weeks of surgery or observation following surgery. Disease-free survival was 14.2 months for patients receiving gemcitabine and 7.5 months for those in the observation group.

It is too soon to tell whether the delay in disease progression will translate into longer overall survival, said study lead author Dr. Peter Neuhaus of Charité University Medical School in Berlin.

In the second study, National Cancer Institute of Canada researchers reported that in a phase III clinical trial with 569 patients with advanced pancreatic cancer, the 1-year survival was 24 percent among patients in the treatment arm that combined gemcitabine with the EGFR inhibitor erlotinib (Tarceva) and 17 percent in the gemcitabine-alone arm. The progression-free survival was 3.75 months for the gemcitabine/erlotinib arm and 3.55 for the gemcitabine plus placebo arm. The median overall survival was still poor: 6.4 months vs 5.9 months.

The difference in median overall survival was statistically significant, said Dr. James Abbruzzese, from the NCI Pancreatic Cancer Specialized Program of Research Excellence at M.D. Anderson Cancer Center. But any enthusiasm about the result, he added, has to be tempered by factors such as the increased toxicity seen in the gemcitabine/erlotinib arm. More work is needed, he suggested, to determine which patients would benefit from receiving erlotinib in addition to gemcitabine.

Early Ovarian Cancer Screening Test Studied

A blood test that measures four proteins detects 96 percent of early ovarian cancers in blinded trials, according to an article published in the May 10 early online edition of the Proceedings of the National Academy of Sciences.

To arrive at the 4-protein panel, researchers at Yale, George Washington University, and the Nevada Cancer Institute screened blood samples from 28 healthy women, 18 women with newly diagnosed ovarian cancer, and 40 women with recurrent disease. Microarray analysis highlighted 35 proteins that were expressed at significantly different levels between the control and patient groups.

The researchers pared down this list based on the biological function and analytic reproduciblity of each highlighted protein. They selected the final four - leptin, prolactin, osteopontin, and insulin-like growth factor II - because each can be measured with off-the-shelf ELISA tests.

The researchers then recruited two new groups: 106 healthy volunteers and 100 women with disease. Blinded ELISA tests measured the blood concentration of each protein in these women. An algorithm then assigned each woman a score of one to four; a one indicated one protein level was abnormal, whereas a four indicated abnormal levels of all four proteins.

After unblinding the tests, the algorithm correctly identified 96 of 100 patients with ovarian cancer, including 23 of 24 patients with stage I or stage II disease. In the healthy group, 6 of 106 women (5.6 percent) were incorrectly identified as having disease.

Underscoring these results as preliminary, Dr. Sudhir Srivastava, director of NCI's Early Detection Research Network, commented, "While the results are exciting, the panel of biomarkers needs to be validated with an expanded number of cases and confounding controls to check the accuracy and specificity, respectively." The Network is discussing collaborating on such validation studies with the study authors.