Healthcare Industry News: sanofi-aventis
News Release - February 27, 2006
Positive Findings from Clinical Studies of QUADRAMET(R) in Prostate Cancer Patients with Metastatic Bone Disease Presented at ASCO Prostate Cancer SymposiumFour Abstracts Describe the Clinical Use of QUADRAMET Both Alone and With Chemotherapy in Patients With Prostate Cancer
PRINCETON, N.J., Feb. 27 (HSMN NewsFeed) -- Cytogen Corporation (Nasdaq: CYTO ) today announced the presentation of data from several clinical studies of QUADRAMET® (samarium Sm-153 lexidronam injection) in prostate cancer patients with metastatic bone disease. The findings were presented this week at the second Prostate Cancer Symposium in San Francisco, a multidisciplinary meeting co-sponsored by the American Society of Clinical Oncology, the American Society for Therapeutic Radiology and Oncology, the Prostate Cancer Foundation, and the Society of Urologic Oncology.
The following four QUADRAMET abstracts were presented at the symposium:
Abstract No. 221 -- "TAXSAM: A new chemo-radiation regimen for bone metastases in hormone refractory prostate cancer."
This phase II study was designed to evaluate the tolerability and efficacy of QUADRAMET in combination with docetaxel (Taxotere®, Aventis Pharmaceuticals, a member of the sanofi-aventis Group) in a combination regimen known as TAXSAM in 29 patients with progressive hormone refractory prostate cancer.
Mean PSA level at baseline for patients enrolled in this study was 838 ng/mL (range 15 to 2330 ng/mL). Docetaxel was administered as a 30-minute infusion at a dose of 30 mg/m2 weekly for 5 weeks. Eighteen to twenty-four hours prior to the fourth administration of docetaxel, the approved dose of QUADRAMET (1 mCi/kg) was injected. Patients received a second cycle of the TAXSAM combination regimen at PSA and/or clinical progression.
According to the results of the study, within 12 weeks after start of the first TAXSAM cycle PSA declines greater than 50% and 75% were seen in 34% and 21% of the patients respectively. The time from start of the TAXSAM regimen until PSA declines greater than 50% and 75% was 38 and 34 days respectively. PSA progression was seen in 69% of the patients, with a median time to PSA progression of 126 days.
Following the first TAXSAM cycle of therapy, grade 3 or 4 neutropenia was seen in three patients, two at week three and one at week six after QUADRAMET administration. One patient had grade 2 thrombocytopenia five weeks after QUADRAMET and there were no occurrences of grade 3 or 4 toxicity.
Seventeen patients opted to receive the second TAXSAM cycle of treatment, with a median interval between the beginning of the first and second treatment cycles of six months. The mean PSA level for these patients was 880 ng/mL (range 23 to 4773 ng/mL). After the second TAXSAM cycle, PSA declines greater than 50% and 75% were seen in 18% and 6% of patients respectively. The time from start of the second TAXSAM cycle until PSA declines greater than 50% and 75% was 40 and 34 days respectively. PSA progression was seen in 65% of the patients, with a median time to PSA progression of 151 days. The incidence of grade 3 or 4 hematological toxicity was only slightly increased after the second TAXSAM cycle.
The study results demonstrated low toxicity with good palliative effect lasting 5 months after the first treatment cycle with the TAXSAM regimen. Time to PSA progression in the first and second treatment cycle was 126 and 151 days respectively.
Abstract No. 223 -- "A phase II trial of maintenance docetaxel and samarium in patients with castration-refractory bone metastases from prostate cancer with response or stabilization after induction docetaxel-estramustine: Preliminary results."
This phase II study was designed to evaluate the efficacy of maintenance treatment using QUADRAMET in combination with docetaxel in patients with progressive hormone refractory prostate cancer with response or stabilization after induction therapy with docetaxel plus estramustine. The primary endpoint of the study was progression-free survival (PFS).
Forty-two patients received induction chemotherapy consisting of docetaxel at a dose of 70 mg/m2 on day two plus estramustine at a dose of 10 mg/kg on days one through five in a cycle that was repeated every three weeks. Patients experiencing a response or stabilization to the treatment after four cycles were switched to a maintenance regimen consisting of docetaxel at a dose of 20 mg/m2 weekly for 6 weeks plus a single injection of QUADRAMET (1 mCi/kg) during week one.
According to the results of the study, of the 36 patients currently evaluable after induction treatment, 25 (69%) patients had a PSA response (defined as a reduction in serum PSA levels of at least 50 percent), 10 (28%) patients had a stabilization of disease, and 1 (3%) patient progressed. Pain response in this group, defined as a decrease in pain intensity by at least two points on a 10 point pain analog visual scale in patients with a baseline pain level greater or equal to 2, was achieved in 16 out of 20 (80%) patients.
Of 29 patients who received the maintenance therapy with QUADRAMET and are currently evaluable, 18 (62%) patients had a PSA response, 4 (14%) patients had a stabilization of disease, and 5 (17%) patients progressed. Two patients (7%) are not evaluable. Pain response in this group was achieved in 16 out of 17 (94%) patients.
The study results demonstrated that maintenance therapy with QUADRAMET was feasible and well-tolerated with most patients experiencing a rapidly reversible and mild (grade 1-2) thrombocytopenia five weeks after the regimen. The study results also demonstrated promising PSA response rates and major pain improvement in patients with hormone refractory prostate cancer and metastatic bone disease.
"The study results presented in these two phase II trials during this important scientific forum represent the largest clinical experience reported to date evaluating the tolerability of concurrent QUADRAMET and docetaxel therapy," said William Goeckeler, Ph.D., Senior Vice President of Operations at Cytogen. "The data, in particular with regard to the manageable and reversible effects on white blood cells and platelets observed in the TAXSAM studies help support the use of QUADRAMET in its approved palliative indication in a contemporary oncology setting where patients may be considered for concurrent or subsequent treatment with taxane based chemotherapy. The data also serve as a basis for further evaluation of the potential additive anticancer effects of these combination approaches. We look forward to the presentation and publication of additional data from researchers at several leading cancer centers who are currently conducting clinical studies evaluating a variety of doses and schedules for combining QUADRAMET with docetaxel and other potentially synergistic agents in a variety of tumor types."
Abstract No. 266 -- "Single and repeated dose samarium Sm-153 lexidronam in prostate cancer: A safety assessment."
In a Phase IV clinical study, patients with metastatic bone disease received multiple administrations of QUADRAMET based on a recurrence of painful symptoms. Overall 134 administrations of 1.0 mCi/kg (the FDA approved dose) were given to 55 patients (range 2-11 doses per patient). The incidence of non-hematologic adverse events following multiple administrations was not increased over that observed following the initial administration in this study or in prior controlled clinical studies. White blood cell (WBC) and platelet toxicities observed following multiple doses were not clinically significantly greater than those observed following the initial dose. No grade 4 platelet or WBC toxicities were observed following multiple doses of QUADRAMET.
Abstract No. 267 -- "Predictors of palliative response for samarium Sm-153 lexidronam: Analysis of data from three randomized controlled blinded trials."
A single dose of QUADRAMET (1 mCi/kg) was administered to 199 patients with painful bone metastases in three prospective randomized blinded trials and demonstrated that QUADRAMET relieved pain and reduced opioid intake in responding patients. One hundred seventy (85%) of the patients in these studies were male and 164 (82%) had hormone refractory prostate cancer. A series of variables were subsequently analyzed to potentially identify predictors of palliative response.
Because radiation resistance has been linked to low hemoglobin (Hgb) levels, baseline Hgb and pain were analyzed before and after QUADRAMET therapy. In addition, QUADRAMET is administered based on body weight, thus heavier patients received higher absolute doses and responses were analyzed to determine if administered dose was predictive of palliative response. Further, intravenously administered QUADRAMET is cleared from the circulation either via skeletal deposition or renal excretion. Skeletal retention has been previously shown to be highly correlated with extent of metastatic bone disease. Consequently, both skeletal retention and baseline creatinine were analyzed as predictors of palliative response.
The study results demonstrate that baseline Hgb, skeletal retention, baseline creatinine, and administered dose do not correlate with palliative response from QUADRAMET and that it is unlikely that any given subset of patients potentially eligible for treatment can be deemed unlikely to respond to therapy.
"These data clearly indicate that multiple doses of QUADRAMET can be administered to patients with painful metastatic bone disease provided normal white blood cell and platelet counts are present at the time of dosing," said A. Oliver Sartor, M.D., lead author for abstracts #266 and #267 and director of the Stanley S. Scott Cancer Center at LSU Medical School in New Orleans, Louisiana. "In addition, analysis of pain response data from controlled clinical trials demonstrate that patients cannot be deemed more or less likely to respond to treatment with QUADRAMET based on the baseline factors examined."
About Prostate Cancer
According to the American Cancer Society (ACS), prostate cancer is the most common cancer, excluding skin cancers, in American men. The ACS estimates that during 2006 about 234,460 new cases of prostate cancer will be diagnosed in the United States and that a little over 1.8 million men in the United States are survivors of prostate cancer. Within the next decade as baby boomer men reach the target age for the diagnosis of prostate cancer, it is anticipated that new prostate cancer cases will increase to 300,000 per year. There is an unmet medical need for treating the disease, particularly for hormone refractory prostate cancer for which therapeutic options are limited.
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 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), predictable and reversible bone marrow toxicity or myelosuppression that tends to return to pretreatment levels after eight weeks, ease of administration, and length of pain relief, lasting an average of four months in responding patients. 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 plain 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.
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 Corporation
Founded in 1980, Cytogen Corporation of Princeton, NJ is a biopharmaceutical company dedicated to improving the lives of patients with cancer by acquiring, developing and commercializing innovative molecules targeting the sites and stages of cancer progression. Cytogen's marketed products include QUADRAMET® (samarium Sm-153 lexidronam injection) and PROSTASCINT® (capromab pendetide) kit for the preparation of Indium In-111 capromab pendetide in the United States. Cytogen also has exclusive United States marketing rights to COMBIDEX® (ferumoxtran-10) for all applications, and the exclusive right to market and sell ferumoxytol (previously Code 7228) for oncology applications in the United States. Cytogen's development pipeline consists of therapeutics targeting prostate-specific membrane antigen (PSMA), a protein highly expressed on the surface of prostate cancer cells and the neovasculature of solid tumors. Full prescribing information for the Company's products is available at http://www.cytogen.com or by calling 800- 833-3533. For more information, please visit the Company's Web site at http://www.cytogen.com, which 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 obtaining additional capital; 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. 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 such forward-looking statements to reflect subsequent events or circumstances.
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