Experimental Drug for Osteosarcoma Improves Overall Survival

Patients with osteosarcoma who received the experimental drug mifamurtide (L-MTP-PE) along with chemotherapy fared better than patients who received chemotherapy alone, researchers are reporting. Osteosarcoma is a rare but often fatal cancer of the bone. The disease typically affects children and young adults, and no new therapies have been introduced in two decades.

The study - conducted by the Children's Oncology Group - was the largest final-stage randomized trial in this disease and included 662 patients with newly diagnosed nonmetastatic osteosarcoma.

After 6 years of follow-up, overall survival was 78 percent in the group receiving mifamurtide plus chemotherapy compared with 70 percent in the group receiving chemotherapy alone. "This is an almost one-third reduction in the risk of death," write Dr. Paul A. Meyers of the Memorial Sloan-Kettering Cancer Center and his colleagues in the February 1 Journal of Clinical Oncology.

A second goal of the NCI-sponsored study was to evaluate the addition of ifosfamide to the three chemotherapy drugs used in the study (cisplatin, doxorubicin, and methotrexate). Adding this agent did not enhance event-free survival or overall survival for patients in the trial.

As an experimental agent, mifamurtide is available only through clinical trials. In 2006, its manufacturer, IDM Pharma, sought approval for its use in treating osteosarcoma from the Food and Drug Administration, but the agency requested more information. The company plans to submit new data showing an overall survival benefit in the disease this year.

Low Risk Seen in Monitoring, Not Treating, Some Prostate Cancers

The vast majority of older men diagnosed with localized prostate cancer who initially forego treatment will die of something other than prostate cancer, researchers said last week. The finding supports the view that actively monitoring the cancer's progression until such time as treatment is needed - a strategy called watchful waiting - is a reasonable response to a diagnosis of early-stage disease for some men.

Using data from NCI's Surveillance, Epidemiology, and End Results (SEER) program, Dr. Grace Lu-Yao of The Cancer Institute of New Jersey and her colleagues asked what happened to 9,000 men who chose active surveillance rather than treatment in an era when screening with the prostate-specific antigen test increased.

After 10 years, 3 to 7 percent of those with low- or moderate-grade disease had died of prostate cancer, compared with 23 percent of men with high-grade cancers. The men were diagnosed between 1992 and 2002 and did not have treatment in the first 6 months after diagnosis. Half were over age 75.

Of the approximately 2,600 men who eventually underwent treatment for the disease, about half delayed therapy for more than a decade. Dr. Lu-Yao presented the results at the first Genitourinary Cancers Symposium in San Francisco, which was sponsored by the American Society of Clinical Oncology (ASCO) and other groups.

Prostate cancers detected by screening tend to progress slowly, and many older men die with the disease, not of it. Furthermore, all therapies for prostate cancer entail risks, and some may lead to impotence or incontinence.

This study provides additional support for the use of active surveillance of localized prostate cancer in older men, particularly among those with lower grade tumors, commented Dr. Howard Sandler of the University of Michigan at the meeting.

Partial Nephrectomy to Treat Small Renal Tumors Underused

The use of partial nephrectomy to treat small, newly diagnosed kidney tumors appears to be vastly underused, researchers from the New York University School of Medicine are reporting.

Studies have shown that partial nephrectomy, only removing the part of the kidney in which a small tumor (typically 4 centimeters or less) resides, produces equivalent outcomes to complete removal of the kidney, or radical nephrectomy, and may prevent the development of a serious side effect, chronic kidney disease. Nevertheless, the researchers reported last week at the ASCO Genitourinary Cancers Symposium, it is offered to only one of every five patients with newly diagnosed, small tumors.

To conduct the study, Dr. William Huang, an assistant professor of urologic oncology, and colleagues analyzed data from NCI's Surveillance, Epidemiology, and End Results program on more than 3,000 patients treated for these small renal tumors from 1995 through 2002. The incidence of kidney tumors has been steadily climbing for several decades, largely due to the incidental discovery of these small tumors during imaging procedures for other problems, Dr. Huang explained during a press briefing.

The research team identified preoperative factors that differed between the more than 2,500 patients with small renal tumors who underwent radical nephrectomy and the 556 who underwent partial nephrectomy. Patients treated with partial nephrectomy were more likely to be younger, male, and treated toward the end of the period covered by the study, which, Dr. Huang noted, could suggest the beginning of a shift toward more partial nephrectomies in patients with small tumors. Women, older patients, and patients with cerebrovascular disease were less likely to have partial nephrectomy.

"Partial nephrectomy is an option for most patients with newly diagnosed kidney tumors," Dr. Huang concluded, "and actually may be a better option because [patients] with kidney tumors often have other comorbid conditions."

More Genetic Clues for Prostate Cancer Found

A new wave of genome scans for prostate cancer ties additional chromosome regions to the disease while also confirming previously reported associations on chromosomes 8 and 17. The results, from three genome-wide association studies published online this month in Nature Genetics, underscore the complexity of prostate cancer genetics.

The first study, from NCI's Cancer Genetic Markers of Susceptibility (CGEMS) initiative, identifies regions of chromosomes 7, 10, and 11 that are associated with moderate increases in the risk of prostate cancer. Dr. Stephen Chanock of NCI's Division of Cancer Epidemiology and Genetics and his colleagues also identify nine other "suggestive" associations and confirm previously reported regions.

Overall, the study "confirms and greatly expands the landscape of genetic factors influencing inherited susceptibility for prostate cancer," the researchers say. Nearly 20 percent of the candidate regions identified in the study are located on chromosomes 5 and 10, which may harbor multiple susceptibility regions for prostate cancer, they note.

The team tested nearly 27,000 single nucleotide polymorphisms (SNPs) in thousands of men with and without the disease. SNPs are variable sites in the genome where a single unit of DNA may change from person to person; the variants may serve as markers of regions containing possible risk factors.

While no susceptibility genes in the regions have been identified yet, the researchers report some candidates. One of the chromosome 10 regions, for instance, contains the gene MSMB, which produces a component of semen and is a potential prostate cancer biomarker. The chromosome 7 region is near a gene linked to endometrial cancer, JAZF1.

In the second study, Dr. Rosalind Eeles of the Institute of Cancer Research, Sutton, U.K., and her colleagues identify seven regions associated with prostate cancer on chromosomes 3, 6, 7, 10, 11, 19, and X. Some of the regions contain genes which may be linked to the disease, including MSMB.

"The results of this study confirm that prostate cancer is genetically complex and help clarify the genetic architecture of prostate cancer," the researchers write.

The third report, from Dr. Julius Gudmundsson and his colleagues at deCODE Genetics in Iceland, identifies associations on chromosomes 2 and X. The variant on chromosome 2 shows a significantly strong association with the more aggressive forms of the disease, they found.

Study Details Risk of NHL in Some Autoimmune Diseases

Researchers found that the risks for developing non-Hodgkin lymphoma (NHL), especially some NHL subtypes, are significantly increased in individuals who reported previously having had certain autoimmune diseases, according to results published online February 8 in Blood.

Autoimmune disorders have been recognized as risk factors for NHL in general, but large-scale assessments of the impact on specific NHL subtypes have been lacking. Researchers from the International Lymphoma Epidemiology Consortium (InterLymph), which is spearheaded by NCI, analyzed pooled data of nearly 30,000 study participants from a dozen case-control studies from across Europe, North America, and Australia. The strongest association was found with Sjögren's syndrome, which showed a 6.5-fold increased risk of NHL overall, including elevated risk for diffuse large B-cell and follicular lymphomas, and a 1,000-fold increased risk for parotid gland marginal zone lymphoma among NHL subtypes.

Lesser but still significant risks for NHL were found among patients with systemic lupus erythematosus (SLE), hemolytic anemia, and, for lymphomas of T-cell origin, among patients with celiac disease and psoriasis. However, inflammatory bowel disorders, type-1 diabetes, sarcoidosis, pernicious anemia, and multiple sclerosis were not associated with risk of NHL or its subtypes.

The InterLymph investigators noted the significance of this study. "Our results further suggest new patterns of associations with some NHL subtypes in specified autoimmune disorders…Besides confirming the known link between all NHL combined and Sjögren's syndrome and SLE, we demonstrated an increased risk of marginal zone and diffuse large B-cell lymphomas in both of these disorders, and an increased risk of specific T-cell NHL subtypes in celiac disease and psoriasis." The researchers also noted that the pattern of associations with NHL subtypes "may harbor clues to lymphomagenesis."