PRINCETON, N.J., Nov. 7 /PRNewswire-FirstCall/ -- Cytogen Corporation today announced results from a Phase 1 clinical trial of QUADRAMET(R) (samarium Sm-153 lexidronam injection) in combination with hormonal therapy and external beam radiation therapy in high-risk, clinically non-metastatic prostate cancer patients. Data from the study indicate that the combination regimen was well tolerated with preliminary anti-tumor activity observed as evidenced by prostate specific antigen or PSA responses. Results were presented at the 48th annual meeting of the American Society for Radiology and Oncology (ASTRO) held November 5-9, 2006, in Philadelphia, PA (Abstract #2238).
Richard Valicenti, M.D., associate professor of radiation oncology at Jefferson Medical College of Thomas Jefferson University and Jefferson’s Kimmel Cancer Center in Philadelphia, has been investigating the neoadjuvant use of QUADRAMET in high risk prostate cancer patients being treated with a combination of hormonal and external beam radiation therapies. The patients are at high risk for having disease which has spread to their bones, but none exhibited any clinical or radiographic signs of bone metastases at the time of treatment.
“The strategy is to use QUADRAMET, a bone-targeted agent, upfront and in combination with standard treatment regimens consisting of a combination of hormones and external beam radiation for high-risk prostate cancer,” said Dr. Valicenti. “We’re hypothesizing that the combination of hormones and radiation could be used to treat microscopic bony metastasis, which could help reduce death rates due to prostate cancer.”
Twenty patients with newly diagnosed high risk (PSA>20 ng/mL and Gleason score greater than or equal to 7; or greater than or equal to T2 and Gleason score greater than or equal to 8) clinically non-metastatic (known as M0) prostate cancer were treated with a regimen consisting of one month of hormonal therapy followed by a single administration of QUADRAMET followed by four more months of hormonal therapy in combination with external beam radiation therapy (RT). RT was administered as 46.8 Gy to the pelvic region and 23.4 Gy to the prostate (total dose of 70.2 Gy). QUADRAMET was administered in escalation doses of 0.25 mCi/kg (4 patients), 0.5 mCi/kg (4 patients), 0.75 mCi/kg (6 patients) and 1.0 mCi/kg (6 patients). The primary endpoint of the study was assessment of the incidence of Grade 3 (or higher) toxicity following all therapy.
Nineteen patients received all planned therapy without any delays and one patient required surgery before the start of RT. Median follow-up time for the entire group was 19 months. Two patients experienced Grade 3 hematologic toxicity and there were no other Grade 3 or 4 side effects. Nadir levels of platelets were significantly lower in the twelve patients receiving QUADRAMET doses >0.5 mCi/kg than in the eight patients receiving less than or equal to 0.5 mCi/kg. At last follow-up, 15 patients had exhibited recovery of testosterone to non-castrate levels following completion of hormonal therapy. Nine of these 15 patients (60%) had not had a rise in PSA above 0.2 ng/mL. The authors concluded that administration of QUADRAMET in combination with hormonal therapy and RT was safe and feasible in patients with high risk M0 prostate cancer and that additional follow-up was necessary to determine of the unexpected PSA response rate was durable in nature.
“The results reported by Dr. Valicenti from this investigator initiated study are certainly very encouraging, particularly with regard to the tolerability of QUADRAMET when administered with external beam radiation,” said William Goeckeler, Ph.D., senior vice president of operations at Cytogen. “Based on these results, we are continuing to support the ongoing Phase 1 study and are working with Dr. Valicenti to expand on this proof of concept for early intervention in larger follow-on studies and to do so in a clinical setting where efficacy findings can be obtained in a time- and cost-effective manner.”
About Metastatic Bone Disease
Each year, more than 100,000 patients in the U.S. develop bone metastases from spread of their primary cancer. Bone is the third most common site of metastatic disease after liver and lung, and spread to bone is associated with considerable morbidity. This includes bone pain and fracture, spinal cord compression, and hypercalcemia. The incidence of bone metastasis is expected to increase over the next decade as patient survival improves due to advances in anticancer therapy. This will make the treatment of this problem more important in the overall management of the surviving cancer patient. The majority of skeletal metastases arise from primary tumors of the thyroid, kidney, lung, prostate, and breast, with the latter two accounting for about 80% of metastatic bone disease. While all bones can be affected, the most common site of disease spread is the spine with the subsequent development of spinal cord compression. In advanced breast cancer, a majority of skeletal events will occur every three to four months resulting in significant morbidity and impaired quality of life.
About QUADRAMET
QUADRAMET is indicated for the relief of pain in patients with confirmed osteoblastic metastatic bone lesions that enhance on radionuclide bone scan.
QUADRAMET is an oncology product indicated for pain relief that pairs the targeting ability of a small molecule, bone-seeking phosphonate (EDTMP) with the therapeutic potential of radiation (samarium Sm-153). Skeletal invasion by prostate, breast, multiple myeloma, and other cancers often creates an imbalance between the normal process of bone destruction and formation. QUADRAMET selectively targets such sites of imbalance, thereby delivering radioactivity to areas of the skeleton that have been invaded by metastatic tumor.
QUADRAMET has demonstrated a range of characteristics that may be advantageous for the treatment of pain arising from metastatic bone disease, including early onset of pain relief (patients may experience pain relief within the first week with maximal relief generally occurring at three to four weeks after injection), length of pain relief, lasting a median of four months in responding patients, and predictable and reversible bone marrow toxicity or myelosuppression that tends to return to pretreatment levels after eight weeks. QUADRAMET is administered as a single intravenous injection, usually on an outpatient basis, and exhibits selective uptake in areas of bone formation with little or no detectable accumulation in soft tissue.
QUADRAMET Safety Profile
QUADRAMET causes bone marrow suppression. In clinical trials, white blood cell counts and platelet counts decreased to a nadir of approximately 40% to 50% of baseline in 123 (95%) of patients within 3 to 5 weeks after QUADRAMET, and tended to return to pretreatment levels by 8 weeks. Because of the unknown potential for additive effects on bone marrow, QUADRAMET should not be given concurrently with chemotherapy or external beam radiation therapy unless the clinical benefits outweigh the risks. Blood counts should be monitored weekly for at least 8 weeks, or until recovery of adequate bone marrow function. Non-hematologic adverse events that occurred in 5% or more of patients and greater than placebo were pain flare (7%), diarrhea (6%), infection (7%), spinal cord compression (6.5%), arrhythmias (5%), and hematuria (5%). Patients who receive QUADRAMET should be advised that for several hours following administration, radioactivity will be present in excreted urine. To help protect themselves and others in their environment, precautions need to be taken for 12 hours following administration.
This press release describes clinical applications that differ from that reported in the QUADRAMET package insert. A copy of the full prescribing information for QUADRAMET, including warnings, precautions, adverse events and other safety information, may be obtained in the U.S. from Cytogen Corporation by calling toll-free 800-833-3533 or by visiting the web site at http://www.cytogen.com, which is not part of this press release.
ABOUT CYTOGEN
Founded in 1980, Cytogen is a biopharmaceutical company dedicated to advancing the care of cancer patients by building, developing, and commercializing a portfolio of specialty pharmaceutical products. The Company’s specialized sales force currently markets QUADRAMET(R), PROSTASCINT(R), and SOLTAMOX(TM) to the U.S. oncology market. QUADRAMET is approved for the treatment of pain in patients whose cancer has spread to the bone, PROSTASCINT is a PSMA-targeting monoclonal antibody-based agent to image the extent and spread of prostate cancer, and SOLTAMOX is the first liquid hormonal therapy approved in the U.S. for the treatment of breast cancer in adjuvant and metastatic settings. In early 2007, Cytogen plans to introduce its fourth approved oncology product to the U.S. market, CAPHOSOL(R), a prescription medical device for the treatment of oral mucositis and dry mouth. The Company is also developing CYT-500, a third-generation radiolabeled antibody to treat prostate cancer. Cytogen’s product-focused strategy focuses on attaining sustainable growth through clinical, commercial, and strategic initiatives.
A copy of the full prescribing information for CAPHOSOL, QUADRAMET, PROSTASCINT, and SOLTAMOX, including box warnings, may be obtained in the U.S. from Cytogen Corporation by calling toll free 800-833-3533 or by visiting Cytogen’s web site at www.cytogen.com. The Company’s website is not part of this press release.
This press release contains certain “forward-looking” statements within the meaning of the Private Securities Litigation Reform Act of 1995 and Section 21E of the Securities Exchange Act of 1934, as amended. All statements, other than statements of historical facts, included in this press release regarding our strategy, future operations, financial position, future revenues, projected costs, prospects, plans and objectives of management are forward-looking statements. Such forward-looking statements involve a number of risks and uncertainties and investors are cautioned not to put any undue reliance on any forward-looking statement. There are a number of important factors that could cause Cytogen’s results to differ materially from those indicated by such forward-looking statements. In particular, Cytogen’s business is subject to a number of significant risks, which include, but are not limited to: the risk of successfully marketing SOLTAMOX and CAPHOSOL; the risk of obtaining the necessary regulatory approvals; the risk of whether products result from development activities; the risk of shifts in the regulatory environment affecting sales of Cytogen’s products such as third-party payor reimbursement issues; the risk associated with Cytogen’s dependence on its partners for development of certain projects, as well as other factors expressed from time to time in Cytogen’s periodic filings with the Securities and Exchange Commission (the “SEC”). As a result, this press release should be read in conjunction with Cytogen’s periodic filings with the SEC. All information in this press release, including the forward-looking statements contained herein, are made only as of the date of this press release, and Cytogen undertakes no obligation to publicly update this information to reflect subsequent events or circumstances.
Cytogen Corporation
CONTACT: Media/Investors, Susan Mesco of Cytogen Corporation,+1-609-750-8213
Web site: http://www.cytogen.com/
