Cytogen: Studies show Quadramet reduces pain in cancer patients with metastatic bone disease

By E. Janene Geiss

Philadelphia, Feb. 27 - Cytogen Corp. said Monday that data from several clinical studies showed Quadramet (samarium Sm-153 lexidronam injection) showed reduction of pain and tolerability 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, according to a company news release.

A phase 2 study designed to evaluate the tolerability and efficacy of Quadramet in combination with docetaxel (Taxotere, Aventis Pharmaceuticals) in a combination regimen known as Taxsam was evaluated in 29 patients with progressive hormone refractory prostate cancer.

Mean PSA level at baseline for patients enrolled in this study was 838 ng/mL, officials said.

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, officials said.

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, officials said.

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, officials said. 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, officials said.

The study results demonstrated low toxicity with good palliative effect lasting five 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, officials said.

Docetaxel combination study

Another phase 2 trial of maintenance docetaxel and samarium in patients with castration-refractory bone metastases from prostate cancer with response or stabilization after induction docetaxel-estramustine 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, officials said.

The primary endpoint of the study was progression-free survival.

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 during week one, officials said.

According to results of the study, of the 36 patients currently evaluable after induction treatment, 25 patients or 69% had a PSA response (defined as a reduction in serum PSA levels of at least 50%), 10 patients or 28% had a stabilization of disease and one patient or 3% progressed, officials said.

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 patients or 80%.

Of 29 patients who received the maintenance therapy with Quadramet and are currently evaluable, 18 patients or 62% had a PSA response, 4 patients or 14% had a stabilization of disease and 5 patients or 17% progressed, officials said.

Two patients or 7% are not evaluable. Pain response in this group was achieved in 16 out of 17 (94%) patients, officials said.

Maintenance therapy feasible

The study results demonstrated that maintenance therapy with Quadramet was feasible and well-tolerated with most patients experiencing a rapidly reversible and mild 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 company said.

"The study results presented in these two phase 2 trials during this important scientific forum represent the largest clinical experience reported to date evaluating the tolerability of concurrent Quadramet and docetaxel therapy," William Goeckeler, senior vice president of operations at Cytogen, said in the release.

"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," he added.

Data from two other studies also were presented at the conference.

Quadramet is indicated for the relief of pain in patients with confirmed osteoblastic metastatic bone lesions that enhance on radionuclide bone scan.

Cytogen is a Princeton, N.J., 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.

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