NCI Cancer Bulletin: A Trusted Source for Cancer Research NewsNCI Cancer Bulletin: A Trusted Source for Cancer Research News
May 10, 2005 • Volume 2 / Number 19 E-Mail This Document  |  Download PDF  |  Bulletin Archive/Search  |  Subscribe

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Cancer Research HighlightsCancer Research Highlights

Combined Chemo Regimen Improves Pancreatic Cancer Outcomes

Pancreatic cancer has a very poor prognosis, with a 1-year survival rate after standard chemotherapy treatment of 17 to 28 percent. But a new Italian study shows that when gemcitabine is administered with three other chemotherapy drugs - cisplatin, epirubicin, and fluorouracil - the combination, called PEFG, doubles survival and causes few side effects. These results were published online on May 9 in The Lancet Oncology.

Fifty-two patients were randomized to the PEFG treatment arm of the study and 47 patients received the standard gemcitabine treatment. Twenty-seven patients in the PEFG arm stopped treatment before completion because of progressive disease, refusal, or a doctor's advice; 37 patients in the control group stopped treatment for similar reasons.

Patients who remained in the PEFG group survived longer than those in the gemcitabine group after 4 months (60 percent vs. 28 percent), 1 year (38.5 percent vs. 21.3 percent), and 2 years (11.5 percent vs. 2.1 percent). Also, patients who received PEFG generally tolerated their treatment better than those in the control group, although two blood disorders, neutropenia and thrombocytopenia, were more common with PEFG.

The authors caution that these findings should be investigated with more patients and note that data on quality of life with treatment was not analyzed with conventional statistical testing. But their conclusion is optimistic: "[Despite limitations], our findings are important because PEFG had manageable toxic effects, did not negatively affect quality of life, and maintained a statistically and clinically relevant outcome advantage."

Study Shows Hormone Reactivates Metastasis Suppressor Genes

A new study by NCI researchers provides strong evidence that the expression of genes that help suppress breast cancer tumor metastases can be increased by the administration of high doses of a hormone used in a common female contraceptive, Depo-Provera. Results of the study by researchers from the Laboratory of Pathology in the NCI Center for Cancer Research are reported in the May 4 Journal of the National Cancer Institute (JNCI).

In two independent experiments using a breast cancer mouse model that reliably duplicates the cancer's metastatic potential, administration of the hormone medroxyprogesterone acetate (MPA) decreased the formation of metastases compared with control mice. Nm23-H1, a member of the Nm23 family of metastasis suppressor genes, was expressed at high levels in 43 percent of lesions from MPA-treated mice, compared with only 13 percent of lesions in untreated mice.

In cell-line studies, MPA reduced the formation of tumor cell colonies, a crucial step in the development of full-blown metastases, by 40 to 50 percent. This effect was blocked by inhibition of Nm23-H1 expression. The metastatic inhibitory effects of MPA were ascribed to its interaction with the glucocorticoid receptor.

The findings, the researchers wrote, validate "a molecular mechanism of action" and "suggest that MPA should be reevaluated" as a potential treatment in aggressive, hormone receptor-negative breast cancer.

Cervical Cancer Screening in HMOs

More than half of cervical cancer cases among 833 women in 7 managed care plans were attributed to lack of Pap testing, according to researchers from NCI's Cancer Research Network. The study, published in the May 4 JNCI, identified all invasive cervical cancer diagnoses made between January 1995 and December 2000 among women who were long-term members of the plans. They then reviewed each woman's medical records for the 3 years prior to diagnosis.

Although 55 percent of cases were linked to a lack of screening, in 31 percent of the cases the Pap test did not detect a presymptomatic cancer or premalignant abnormality; in 12 percent of cases, a premalignant abnormality was detected, but cancer diagnosis was delayed because of follow-up failure. Women older than 39 and women living in a high-poverty area or with low educational levels had significantly higher odds of not having had a Pap test.

The authors suggest that access to health care, adherence to recommendations, and screening test performance may be issues for which interventions might be developed. They note that to reduce invasive cervical cancer among women with access to screening and treatment, Pap screening adherence should be increased. Additionally, new or improved strategies in specimen collection in the clinic and in interpretation in the cytology lab might allow better detection of cervical abnormalities.

HNPCC Screening Test Developed

The researchers who discovered the genetic mutations responsible for hereditary non-polyposis colon cancer (HNPCC) - also called Lynch syndrome - are now developing a series of screening tests for the disease, based on a study reported in the May 5 New England Journal of Medicine. Lynch syndrome causes about 3 to 4 percent of colon cancers.

Dr. Albert de la Chapelle and colleagues at the Ohio State University Comprehensive Cancer Center write that "molecular screening of patients with colorectal adenocarcinoma for the Lynch syndrome identified mutations in patients and their family members that otherwise would not have been detected."

The team screened 1,066 colon cancer patients with two different techniques to highlight microsatellite instabilities, a hallmark of Lynch syndrome in which certain easily identifiable regions of the genome lengthen or shorten. Although the team did not compare the techniques directly, immunohistochemical staining and the genotyping method gave similar results. Each method identified 21 of 23 patients that carried the Lynch syndrome mutations.

Family members of the Lynch syndrome patients were then counseled and offered the screening tests. Of these, 117 chose to be tested and 52 (44 percent) were found to carry the telltale mutations.

In an accompanying editorial, Drs. Henry T. Lynch and Patrick M. Lynch write that the new screening process is an improvement over one existing standard, "the Amsterdam criteria," which relies on clinical observations. Only 3 of the 23 patients with Lynch syndrome in the new study met the Amsterdam criteria, they note.