"Phase 1 study of docetaxel and (153)Sm-lexidronam repetitively administered for castrate metastatic prostate cancer" by Morris M.J. et al. Memorial Sloan-Kettering Cancer Center (Abstract No. 5152, Poster No. L6)
Despite a favorable safety and efficacy profile, the routine and repetitive use of QUADRAMET for the palliation of pain from cancer that has spread to the bone has historically been limited in combination settings due to concerns regarding the potential for overlapping toxicities.
Accordingly, the objective of this open-label Company-sponsored Phase 1 study was to evaluate the safety and feasibility of repetitive co-administration of docetaxel and QUADRAMET in twenty-eight hormone-refractory prostate cancer patients with progressive disease and at least three bone metastases confirmed through a bone scan. In addition, early clinical data suggest synergistic effects between QUADRAMET and chemotherapy; therefore, as a secondary objective the anti-tumor effects of the combined regimen were also assessed.
Patients received repeated escalating doses of the combination of QUADRAMET (at doses up to the full FDA-approved doses of 1.0 mCi/kg, given every six to nine weeks) and docetaxel (at doses up to 75 mg/m2 given every three weeks). Dose -limiting toxicity (DLT) was evaluated based on the first cycle of treatment and DLT was not reached in 21 patients who received the combination regimen including patients who received the full FDA approved doses of each agent. Further, all patients' platelet and neutrophil counts recovered to protocol defined levels and times allowing for re-treatment after cycle one. At baseline, median Gleason Score was eight, median PSA values were 162 ng/ml and 43% of patients had previously received taxane-based chemotherapy. Following treatment, 12 out of 21 patients achieved a 50% or greater decline in PSA. Data on progression-free survival are pending.
The authors concluded that repetitive dosing of QUADRAMET and docetaxel was feasible and well-tolerated. Clinically significant hematologic toxicity was rare and does not appear to be related to dose or disease burden. Plans are underway for a multi-center Phase 2 study with Memorial Sloan-Kettering Cancer Center and other leading prostate cancer centers.
"With bone pain representing a significant quality-of-life concern for patients with metastatic prostate cancer, we wanted to see if we could combine QUADRAMET, an FDA-approved drug to treat bone pain, with docetaxel, an FDA-approved drug to treat late stage prostate cancer, and administer both at their respective, FDA-approved therapeutic doses without compromising patient safety," explained Michael J. Morris, M.D., an oncologist specializing in prostate cancer at Memorial Sloan-Kettering Cancer Center. "The Phase 1 data demonstrate that repeated doses of QUADRAMET are safe and do not appear to impair the effective delivery of docetaxel in most patients."
"Phase 1 trial with combination of docetaxel (D) plus samarium-13 (Sm 153) in patients (pts) with hormone refractory prostate cancer (HRPC)" by Sinibaldi et al. Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD (Abstract No. 15547, published in the ASCO proceedings)
Simil ar to the rationale for the aforementioned, Memorial Sloan-Kettering study, this Phase 1 trial was designed to evaluate toxicity and preliminary efficacy of the combination of docetaxel plus QUADRAMET administered sequentially in advanced HRPC.
Preliminary data was published for 10 patients who received repeated doses of the combination of QUADRAMET (at the full FDA-approved doses of 1.0 mCi/kg every 12 weeks for a maximum of two cycles) and escalating doses of docetaxel (at doses up to 75 mg/m(2) every three weeks). All patients had bone metastases and all symptomatic patients (seven of seven) had improvement of pain. Median baseline PSA was 77 ng/ml and four of 10 patients achieved a 50% decline that lasted for four or more weeks.
The authors concluded that the data suggest that the combination of QUADRAMET and docetaxel may be administered simultaneously at the full approved doses in extensively pretreated HRPC patients with acceptable toxicity and significant activity.
"A Phase 2 trial of docetaxel and samarium in patients with bone metastases from castration-refractory prostate cancer (CRPC)" by Laplanche, A. et al. (Abstract No. 5122, Poster No. G4)
In a prospective, Phase 2 investigator-sponsored trial investigators reported on long-term pain responses, disease progression and survival in patients treated with a combination of QUADRAMET and docetaxel/estramustine. Forty-three patients with CRPC were administered docetaxel (70 mg/m(2) per cycle) on three week intervals for three cycles which was followed by a weekly dosing schedule of docetaxel (20 mg/m(2) per cycle for six cycles) during which a single dose of QUADRAMET (1.0 mCi/kg) was administered in combination with the first dose of docetaxel. The authors reported a median prostate specific antigen (PSA) progression-free survival rate of seven months, a median survival of approximately 30 months, and concluded the combination was feasible, well tolerated, and associated with a promising pain response rate of 69% (based on a decrease of at least two points on a 10 point scale.)
Society of Nuclear Medicine Abstracts
Cytogen also reported today the presentation of a number of abstracts related to investigator-sponsored studies with QUADRAMET or Cytogen's monoclonal antibody-based molecular imaging agent for prostate cancer, PROSTASCINT(R) (capromab pendetide), at the 54th Annual Meeting of the Society of Nuclear Medicine taking place through June 6, 2007 in Washington, DC. The abstract titles and publication numbers are as follows:
"Combination of radionuclide therapy using Sm-153-Lexidronam and chemotherapy in patients with bone metastases of hormone refractory prostate cancer (HRPC): First results", by Nestle, et al. Saarland University Medical Center, Homburg/Saar, Germany (Abstract No. 127, Sunday, June 3, 2007, 5:03 PM)
"Radiation safety of outpatient therapy in patients receiving high-dose Sm-153 EDTMP treatment: A prospective study", by Bartosh et al., The University of Texas MD Anderson Cancer Center, Houston, Texas (Abstract No. 2027, Monday June 4, 2007, 1:42 PM)
"Comparison of animal biodistribution of EDTMP labeled with various beta emitting lanthanides", by Sohaib, et al., Pakistan Institute of Nuclear Sciences and Technology (PINSTECH), Islamabad, Pakistan (Abstract No. 461, Tuesday June 5, 2007, 3:18 PM)
"ProstaScint imaging - Reviewing the fundamentals", by Sureshbabu, et al., Excel Diagnostics Imaging Clinics, Houston, Texas (Abstract No. 2103, Monday June 4, 2007, 2:30 PM)
"Use of SPECT/CT in tumor localization: SPECT/CT versus planar and SPECT imaging in tumor localization" by Levi, et al. Florida Hospital College of Health Sciences, Orlando, Florida (Abstract No. 2228, Monday, June 4, 2007, 8:50 AM)
"Added value of SPECT-CT in patients explored by 111In-Capromab Pendetide (ProstaScint)", by Belhocine, et al. (Abstract No. 653, Wednesday June 6, 2007, 9:45 AM)
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 references clinical applications that differ from that reported in the QUADRAMET package insert.
QUADRAMET 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 radiati on 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.
Cytogen is a specialty pharmaceutical company dedicated to advancing the treatment and care of patients by building, developing, and commercializing a portfolio of oncology products. The Company's specialized sales force currently markets three therapeutic products and one diagnostic product to the U.S. oncology market. CAPHOSOL(R) is an advanced electrolyte solution for the treatment of oral mucositis and dry mouth that is approved in the U.S. as a prescription medical device. QUADRAMET(R) (samarium Sm-153 lexidronam injection) is approved for the treatment of pain in patients whose cancer has spread to the bone. PROSTASCINT(R) (capromab pendetide) is a PSMA-targeting monoclonal antibody-based agent to image the extent and spread of prostate cancer and SOLTAMOX(TM) (tamoxifen citrate) is the first liquid hormonal therapy approved in the U.S. for the treatment of breast cancer in adjuvant and metastatic settings. The Company is also developing CYT-500, a third-generation radiolabeled antibody to treat prostate cancer. Cytogen's product-focused strategy centers on attaining sustainable growth through clinical, commercial, and strategic initiatives.
A copy of the full prescribing information for CAPHOSOL, QUADRAMET, PROSTASCINT and SOLTAMOX, including Boxed Warnings, warnings, p recautions, 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. 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 obtaining the necessary regulatory approvals for new QUADRAMET or PROSTASCINT indications, 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 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.
Susan M. Mesco, 609-750-8213