Experimental agent denosumab active against giant cell tumor of bone

In a small phase II study, 87% of patients with recurrent or unresectable giant cell tumor of bone had a significant tumor response to the humanized monoclonal antibody denosumab – a finding that warrants further exploration of the experimental agent as long-term therapy for this rare cancer, according to an investigator at the annual meeting of the American Society of Clinical Oncology.
A total of 9 of 15 patients in an interim analysis had a histologic response indicating either decimation or elimination of the tumor by denosumab, and 4 had a radiographic response indicating stable disease with no evidence of additional progression, said Dr. David Thomas, group leader of the Sarcoma Genomics and Genetics Laboratory at Peter MacCallum Cancer Centre in East Melbourne, Victoria, Australia.
Denosumab targets the RANK ligand (RANKL), a mediator of osteoclast formation, function, and survival.
”Histologic results showed almost complete or complete elimination of the giant cells,” Dr. Thomas said in a clinical science symposium. “In some cases, elimination of the giant cells was associated with reductions in RANKL, especially in the tumor, raising the question of whether with prolonged treatment with this agent we might be able to eliminate the cells that drive giant cell tumor of bone.”
The investigators also observed that some patients in the study, funded by Amgen Inc., the maker of denosumab, had evidence of reduction in tumor activity on positron emission tomography scans, stabilization of tumors in bone, a decrease in soft tissue expansion outside the bone, and, in three patients, evidence of new bone formation and repair.
Nine patients also had a clinical benefit, reflected as reductions in pain and increased range of motion sufficient to allow some of them to return to work.
A total of 35 adults with either resectable or unresectable giant cell tumors were enrolled in the 1-year, open label phase II study. They received 120 mg of denosumab once monthly, with loading doses on the 8th and 15th days of the first treatment month.
The primary study end point was tumor response, defined as an elimination of at least 90% of giant cells, or no radiographic evidence of progression of the target lesion at week 25.
In all, 15 patients were evaluable for efficacy, based on the availability of pre- and posttreatment radiology or histology assessments. The authors found that 13 of the 15 (87%) had a tumor response: 9 of 9 with a histologic response, and 4 of 6 with a radiographic response.
Adverse events occurred in 19 of the 24 patients who have received denosumab thus far in the study. The most frequent events were headache and nasopharyngitis, each occurring in three patients. Two patients had serious adverse events – one case of depression and one of nausea and pain – but these were deemed to be unrelated to the treatment. There were also three unspecified grade 3 and higher adverse events, also determined to be unrelated to the treatment.

Provenge Significantly Improves Survival Advanced Prostate Cancer

Dendreon Corporation has announced that Provenge, the Company's investigational immunotherapy for the treatment of prostate cancer, significantly improved survival in men with asymptomatic, metastatic androgen-independent (hormone-refractory) prostate cancer when compared to patients who were receiving placebo.This is a three-year intent-to-treat analysis of the Company's first randomized Phase 3 clinical study, in which patients receiving Provenge had a 4.5 month improvement in their median survival and a greater than 3-fold increase in survival at 36 months when compared to patients receiving placebo. Provenge is designed to stimulate a patient's immune system against prostate cancer cells. It is developed through Dendreon's proprietary Antigen Delivery Cassette technology, which utilizes a recombinant form of an antigen found in 95 percent of prostate cancers, prostatic acid phosphatase (PAP). Provenge is being further evaluated in an ongoing, another pivotal Phase 3 trial (D9902B) under a Special Protocol Assessment agreement with the U.S. Food and Drug Administration.To learn more about the trial, go to www.dendreon.com.

breast cancer screening... a necessity... bt when??

The U.S. Preventive Services Task Force (USPSTF) recommends screening mammography, with or without clinical breast examination (CBE), every 1-2 years for women aged 40 and older.
The USPSTF found fair evidence that mammography screening every 12-33 months significantly reduces mortality from breast cancer. Evidence is strongest for women aged 50-69, the age group generally included in screening trials. For women aged 40-49, the evidence that screening mammography reduces mortality from breast cancer is weaker, and the absolute benefit of mammography is smaller, than it is for older women. Most, but not all, studies indicate a mortality benefit for women undergoing mammography at ages 40-49, but the delay in observed benefit in women younger than 50 makes it difficult to determine the incremental benefit of beginning screening at age 40 rather than at age 50. A useful reminder site to carrying out yrly mammograms.... js copy n paste on the address site....https://acsremindme.com/hma/modify_subscription.php?CID=288

Adjuvant systemic therapy for breast cancers: overview

Any invasive breast cancer is associated with some risk of distant organ micrometastatic disease, and the risk of breast cancer mortality is reduced by delivery of systemic therapy as adjuvant treatment after primary surgery. The absolute benefit from adjuvant therapy will depend on the patient's underlying risk of relapse. Patients who have node-positive breast cancer therefore have the largest-magnitude benefit from adjuvant therapy. Conversely, patients who have small, node-negative cancers must balance the toxicity of systemic therapy against the estimated risk of metastatic disease, because some of these patients will have an excellent outcome with primary surgery alone. Web-based computerized programs such aswww.adjuvantonline.com provide patients and clinicians with a summary of calculated risks versus benefits from systemic therapy based upon primary clinicopathologic features. Genetic profiling and assignment of a recurrence score via the Oncotype DX test can be helpful in determining benefit from adjuvant chemotherapy in addition to endocrine therapy for ER-positive, node-negative cases.
ER-responsive breast cancer (ER- or PR-positive disease) will usually require tamoxifen or an aromatase inhibitor if the patient is postmenopausal. Chemotherapy is recommended for high-risk endocrine-responsive disease (eg, node-positive breast cancer), and for any endocrine-resistant breast cancer that is deemed appropriate for systemic treatment. Trastuzamab is indicated as targeted therapy to follow chemotherapy for HER-2/neu-overexpressing cancers. for further details ..... read ..Surgical Clinics of North America - Volume 87, Issue 2 (April 2007