Data suggests potential role of Quadramet in conjunction with chemotherapy for the treatment of acute myeloid leukemia

Sep 20 2004

Cytogen Corporation today announced the presentation of new data relating to its lead therapeutic product Quadramet (samarium Sm-153 lexidronam injection) during the 36th Congress of the International Society of Pediatric Oncology (SIOP).

The data were reported by independent investigators at the Mayo Clinic who are evaluating the use of high dose Quadramet in conjunction with chemotherapy for the treatment of acute myeloid leukemia (AML).

"While Quadramet is currently available as a non-opioid alternative for rapid and long-acting pain relief from metastatic bone disease associated with various cancers, the investigational data presented today further demonstrate how Quadramet's novel mechanism of action may enhance anticancer activity when used in combination with melphalan and other therapeutic agents," said Michael D. Becker, Cytogen's President and Chief Executive Officer. "Supplemented by both ongoing and additional clinical studies, we believe that Quadramet could prove to be an important bone-seeking therapy for cancer patients."

Four high-risk AML patients (age range 15 to 20 years) received a significantly higher dose of Quadramet than used for palliative indications prior to preparative chemotherapy conditioning regimens with melphalan (n = 3) or busulfan/cyclophosphamide (n = 1) and hematopoietic stem cell transplantation. High-risk features included secondary AML and a chromosomal defect known as monosomy 7 (n = 1), chemotherapy induction failure (n = 1), and AML in relapse (n = 2). The dose of Quadramet administered to the patients was 19 mCi/kg (n = 1) and 30 mCi/kg (n = 3), compared to the approved 1 mCi/kg dose used in the palliative setting.

"As a result of its highly specific targeting to bone, Quadramet provides a novel method for delivering radiation, and our results in AML patients indicates that, even at much higher doses than are typically administered, the treatment was well tolerated," said Peter Anderson, M.D., Ph.D., a pediatric oncologist at the Mayo Clinic and lead investigator in the study. "Moreover, the positive clinical responses observed in this group of high-risk patients indicate that further evaluation of this therapeutic approach is warranted."

Complete cytogenetic and morphologic remission of AML was seen on follow- up marrow aspirate and biopsy in all patients. Two high-risk AML patients remain in continuous complete remission with excellent quality of life (one patient greater than 1-year, another greater than 3-years) following the treatment regimen with high dose Quadramet. Two patients had a complete response and subsequently relapsed (one patient at 64 days and the other at 6 months). No hemorrhagic cystitis, nephrotoxicity, or serious infections were seen.

"The group at the Mayo Clinic has pioneered investigations into the use of high dose Quadramet in the treatment of hematologic malignancies," said William Goeckeler, Ph.D., Senior Vice President of Operations at Cytogen. "These results are exciting not only for the positive clinical responses reported but also because they add to the growing body of data on the lack of renal and other non-hematologic toxicity associated with the use of these very high doses of Quadramet."

Quadramet is a targeted oncology product consisting of a short half-life therapeutic radionuclide (Samarium-153) bound to a small-molecule, bone- seeking phosphonate (EDTMP) that selectively concentrates in osteoblastic sites (areas of new bone formation), thereby delivering radioactivity in areas that have been invaded by metastatic tumor. Osteoblastic bone lesions can be associated with advanced prostate, breast, multiple myeloma and other cancers that have metastasized to bone, which can cause pain that may be severe and difficult to treat. Though indicated for pain palliation, ongoing clinical studies are investigating whether Quadramet may have direct anticancer activity and may also enhance the cytotoxic activity of chemotherapeutics and other agents.

Research indicates that many patients with advanced cancer develop metastatic bone disease, the spread of cancerous cells from the original tumor to bones. It is estimated that 350,000 people die with metastatic bone disease annually in the United States. Pain is one of the most common symptoms associated with metastatic bone disease. Studies have shown that many patients with cancer (especially older adults) do not receive adequate pain relief. Effective pain control can help patients stay involved not only in their cancer treatment but also in the activities of daily living.

Quadramet is indicated for the relief of pain in patients with confirmed osteoblastic metastatic bone lesions that enhance on radionuclide bone scan. This press release describes clinical applications that differ from that reported in the Quadramet package insert. Quadramet should not be given concurrently with chemotherapy or external beam radiation therapy unless the benefit outweighs the risk. Quadramet should not be given after either of these treatments until there has been time for adequate marrow recovery.