Archive for December, 2009

By: Walter Alexander

NEW ORLEANS, LA – Researchers said that Phase II clinical trials suggest that the peptibody protein romiplostim could reduce the risk of low platelet counts – thrombocytopenia – in patients undergoing lenalidomide therapy for myelodysplastic syndrome.

While lenalidomide is effective in reducing symptoms and progression of myelodysplastic disease, the treatment can result in life-threatening bouts of thrombocytopenia, researchers said at the 51st annual meeting of the American Society of Hematology.

“This preliminary analysis suggests that romiplostim may reduce the rate of clinically significant thrombocytopenic events while increasing platelet counts in lower-risk MDS patients receiving lenalidomide,” Roger. Lyons, MD, of the Cancer Care Centers of South Texas, US Oncology, San Antonio, TX, said.
Thrombocytopenia, which occurs in 40-65% of patients with myelodysplastic syndrome over their disease course, can cause hemorrhagic complications, including death. Platelet transfusions are the only current supportive treatment for thrombocytopenia in these patients.

Romiplostim is designed to increase platelet production by binding to and activating the thrombopoietin receptor. It is indicated for treatment of adult chronic immune thrombocytopenia in patients with insufficient responses to corticosteroids, immunoglobulins or splenectomy.

In the multicenter, randomized, placebo-controlled trial of romiplostim, Dr. Lyons, evaluated the effect of romiplostim on the incidence of clinically significant thrombocytopenic events and on safety in patients with low or intermediate risk myelodysplastic syndrome.

Patients who were candidates for lenalidomide were randomized to receive to placebo, 500 µg romiplostim, or 750 µg romiplostim by weekly subcutaneous injections in combination with lenalidomide.
Among 39 enrolled patients, median age was 74 years.

Researchers saw higher platelet counts with romiplostim than with placebo throughout 17 weeks of follow-up.

Clinically significant thrombocytopenic events occurred in 8 (67%) placebo group patients, in 4 (29%) romiplostim 500 µg group patients and in 7 (54%) romiplostim 750 µg group patients. Platelet transfusions were required in 2 (25%) placebo group patients, in 1 (7%) romiplostim 500 µg patient and in 4 (31%) romiplostim 750 µg patients.

Treatment-related serious adverse events were reported in 1 (8%) patient only in the romiplostim 500 µg group.

- MFP Wire Services
- 12-31-2009

WASHINGTON, DC – It’s the ultimate goal in the treatment of cancer: tailoring a person’s therapy based on his or her genetic makeup. While a lofty goal, scientists are steadily moving forward, rapidly exploiting new technologies. Researchers at Georgetown Lombardi Comprehensive Cancer Center report a significant advance in this field of research using a new chip that looks for hundreds of mutations in dozen of genes.

The goal of personalized medicine is to determine the best treatment and the optimal dose carrying the fewest side-effect, especially as new drugs are discovered and treatment options increase. Variations in our genes encode proteins, which impact how a drug is metabolized or taken in by the cells. This directly impacts the drug’s effectiveness and the kinds of side-effects that may be caused by its toxicity.

“Currently, available genotyping tools test only a few genes at a time,” explains John F. Deeken, a pharmacogentic researcher at Lombardi. “With a new chip called DMET, as many as 170 genes can be examined for more than a thousand variations. This type of turn-key testing, if validated, could eventually replace highly-specialized, time-consuming and labor-intensive testing — thus allowing more institutes the opportunity to pursue genotyping and pharmocogenetic research. That alone would be a significant development for our field and for expediting the research many of us believe is the future of medicine.”

Such a development is particularly critical for cancer research, both in terms of drug discovery and treatment. Genetic variability among patients in cancer clinical trials is not commonly taken into account, a factor that could skew dosage amounts and doom an otherwise promising new drug. A more simple and faster test could be readily incorporated into treatment trials.

In his paper published online today in The Pharmacogenomics Journal, Deeken and colleagues report results of the new genotyping platform called DMET, or drug-metabolizing enzymes and transporters, (Affymetrix, Inc., Santa Clara, Calif.). The DMET “casts a wider net,” screening for 1256 genetic variations in 170 genes involved in drug absorption, distribution, metabolism and excretion.

Deeken says one of the main obstacles facing pharmocogenetic researchers like himself is the lack of a proven and relatively quick technology for genotyping. “DMET appears to offer great promise in this field as a reliable test unveiling genetic variations that correlated with drug effectiveness and toxicity,” says Deeken. “Still, DMET isn’t yet ready for primetime in terms of having received FDA approval, but we’re getting closer.”

Deeken serves as a consultant to Sanofi-Aventis, the manufacturer of docetaxel, a drug involved in the current reported study. Three other authors are employees of Affymetrix, the manufacturer of the DMET platform. The study was done in part at the National Cancer Institute and supported by funding from the National Institutes of Health.

- MFP Wire Services
- 12-31-2009

HEINDELBERG, GERMANY – The prevalence of left-sided advanced colorectal neoplasms was lower in participants in a community setting, but not right-sided advanced neoplams, who had received a colonoscopy in the preceding 10 years, according to a new study recently published online in the Journal of the National Cancer Institute.

Effectiveness of colonoscopy in preventing colorectal cancer has been studied, but evidence from community settings is sparse, especially with respect to anatomical site.

To study this, Hermann Brenner, M.D., MPH, of the Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, in Heidelberg, Germany, and colleagues conducted a cross-sectional study among 3,287 participants of screening colonoscopy aged 55 years or older from the state of Saarland between May 2005 and December 2007. Previous colonoscopy history was obtained by standardized questionnaire, and its association with prevalence of advanced colorectal neoplasms was estimated.

Advanced colorectal neoplasms were detected in 308 (11.4%) of the 2,701 participants with no previous colonoscopy compared with 36 (6.1%) of the 586 participants who had undergone colonoscopy within the preceding 10 years. Prevalence of left-sided advanced colorectal neoplasms, but not right-sided advanced neoplasms, was substantially lower within a 10-year period after colonoscopy in this community setting.

“Although a strong protective effect of colonoscopy from colorectal neoplasms has been established through previous studies, our results add to the evidence that this effect is much stronger in, if not confined to, the left colon and rectum, at least in the community setting,” the authors write.

In an accompanying editorial, Nancy N. Baxter, M.D., Ph.D., of the Division of General Surgery at St Michael’s Hospital, University of Toronto, and Linda Rabeneck, M.D., MPH, of the Department of Health Policy, Management, and Evaluation at the University of Toronto and Odette Cancer Centre, Sunnybrook Health Sciences Centre Toronto, note that these results are an important contribution to the growing body of literature of colonoscopy effectiveness research but still leave questions about the incremental benefits of screening colonoscopy. The editorialists point to some of the limitations of the literature.

“Simply put, is the effectiveness of colonoscopy ‘good enough’ for population-based screening?” they write. “As more observational evidence accumulates, the answer to this question becomes less certain.”

- MFP Wire Services
- 12-31-2009